Trial Outcomes & Findings for FOLFIRINOX + RT for Pancreatic Cancer (NCT NCT01591733)

Last Updated: 2021-05-28

Results Overview

The rate of R0 resection of patients with borderline-resectable adenocarcinoma of the head of the pancreas, along with borderline-resectable and resectable adenocarcinoma of the body and tail of the pancreas. R0 resection means that following surgery, no cancer cells are seen microscopically at the resection margin.

Recruitment status

UNKNOWN

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

Post-surgery (about 4 months post baseline)

Results posted on

2021-05-28

Participant Flow

Participant milestones

Participant milestones
Measure	FOLFIRINOX + Radiation All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Overall Study STARTED	48
Overall Study COMPLETED	48
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

FOLFIRINOX + RT for Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FOLFIRINOX + Radiation n=48 Participants All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	48 Participants n=5 Participants
CA19-9 Level <35 U/ml (Normal)	12 Participants n=5 Participants
CA19-9 Level ≥35 U/ml (elevated)	36 Participants n=5 Participants
CEA Level <3.4 ng/ml (normal)	23 Participants n=5 Participants
CEA Level ≥3.4 ng/ml (elevated)	25 Participants n=5 Participants
Pancreatic Tumor Site Head	35 Participants n=5 Participants
Pancreatic Tumor Site Body	11 Participants n=5 Participants
Pancreatic Tumor Site Tail	2 Participants n=5 Participants
Tumor Size	3.75 Centimeters (cm) n=5 Participants
Vessel Involvement Venous	28 Participants n=5 Participants
Vessel Involvement Arterial	7 Participants n=5 Participants
Vessel Involvement Both	12 Participants n=5 Participants
Vessel Involvement None	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Post-surgery (about 4 months post baseline)

Outcome measures

Outcome measures
Measure	All Eligible - FOLFIRINOX + Radiation n=48 Participants The overall study population All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy	Resected Participants - FOLFIRINOX + Radiation n=32 Participants The participants that were resected. All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Rate of R0 Resection	31 Participants	31 Participants

SECONDARY outcome

Timeframe: From the start of treatment until death or disease progression, median duration of follow-up of 14.7 months

The median progression free survival as measured from the start of treatment until the time of disease progression or death, whichever occurs first. Disease status was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Disease progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesion, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	All Eligible - FOLFIRINOX + Radiation n=48 Participants The overall study population All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy	Resected Participants - FOLFIRINOX + Radiation The participants that were resected. All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Median Progression-Free Survival	14.7 Months Interval 10.5 to Upper bound is not defined due to skewed survival data (participants still surviving).	—

SECONDARY outcome

Timeframe: From the start of treatment until the time of death, median duration of follow-up of 37.7 months

Median overall survival, as measured from the start of treatment until the time of death.

Outcome measures

Outcome measures
Measure	All Eligible - FOLFIRINOX + Radiation n=48 Participants The overall study population All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy	Resected Participants - FOLFIRINOX + Radiation The participants that were resected. All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Median Overall Survival	37.7 Months Interval 19.4 to Upper bound is not defined due to skewed survival data (participants still surviving).	—

SECONDARY outcome

Timeframe: From the start of treatment until the end of chemoradiation, about 4 months

Frequency of grade 3 or greater adverse events deemed related to FOLFIRINOX+short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).

Outcome measures

Outcome measures
Measure	All Eligible - FOLFIRINOX + Radiation n=48 Participants The overall study population All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy	Resected Participants - FOLFIRINOX + Radiation The participants that were resected. All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Diarrhea	5 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Neutropenia	2 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Febrile neutropenia	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Lymphopenia	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Thrombocytopenia	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Anemia	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Elevated alkaline phosphatase	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Elevated bilirubin	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Elevated AST/ALT	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Peripheral neuropathy	2 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Abdominal pain	1 Participants	—
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation Constipation	1 Participants	—

SECONDARY outcome

Timeframe: At the time of surgery, 30 days post-surgery

Population: The participants that underwent surgery

The number of participants with surgery related any grade adverse events following pancreaticoduodenectomy or distal pancreatectomy after receiving preoperative FOLFIRINOX and preoperative short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).

Outcome measures

Outcome measures
Measure	All Eligible - FOLFIRINOX + Radiation n=32 Participants The overall study population All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy	Resected Participants - FOLFIRINOX + Radiation The participants that were resected. All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
The Proportion of Participants With Surgery Related Adverse Events	0.375 proportion of participants Interval 0.233 to 0.536	—

SECONDARY outcome

Timeframe: 30 days post surgery (about 6 months from baseline)

Population: The number of participants that underwent surgery

The number of participants that died within 30 days after undergoing pancreaticoduodenectomy or distal pancreatectomy.

Outcome measures

Outcome measures
Measure	All Eligible - FOLFIRINOX + Radiation n=32 Participants The overall study population All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy	Resected Participants - FOLFIRINOX + Radiation The participants that were resected. All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
30 Day Post-operative Mortality Rate	0 Participants	—

SECONDARY outcome

Timeframe: Baseline, Post surgery

To determine the rate of pathologic down-staging among participants that underwent pancreaticoduodenectomy or distal pancreatectomy. The pathologic downstaging rate is the proportion of patients with the primary tumor and nodes downstaged based on final pathology of the surgical specimen.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until the end of treatment with FOLFIRINOX, or until disease progression (median duration of follow-up of approximately 14 months)

Population: The first 5 participants treated who only received 4 cycles of FOLFIRINOX instead of 8 were not included in the analysis of local control.

The number of participants that achieved local control. Local control was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Local Failure is defined as progression of the primary tumor, or to the reappearance of tumor at the primary site.

Outcome measures

Outcome measures
Measure	All Eligible - FOLFIRINOX + Radiation n=43 Participants The overall study population All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy	Resected Participants - FOLFIRINOX + Radiation The participants that were resected. All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Local Control Rates	32 Participants	—

SECONDARY outcome

Timeframe: 2 years

To correlate mutational analysis biomarkers (SNaPSHOT assay) with response to treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Patient-reported outcomes: We will use descriptive statistics to describe Quality of Life (QOL) (EORTC QLQ-C30), symptom burden (ESAS-r) and mood (HADS) for the entire study cohort.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Summary of the number of hospitalizations, intensive care unit (ICU) stays, emergency department (ED) stays, and palliative care use for the study population.

Outcome measures

Outcome data not reported

Adverse Events

FOLFIRINOX + Radiation

Serious events: 24 serious events

Other events: 48 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	FOLFIRINOX + Radiation n=48 participants at risk All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Gastrointestinal disorders Abdominal pain	2.1% 1/48 • Number of events 2 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Alanine aminotransferase increased	4.2% 2/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Alkaline phosphatase increased	4.2% 2/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Immune system disorders Anaphylaxis	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Blood and lymphatic system disorders Anemia	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Anorexia	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Aspartate aminotransferase increased	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Blood bilirubin increased	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Constipation	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Diarrhea	14.6% 7/48 • Number of events 11 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Fatigue	4.2% 2/48 • Number of events 2 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Blood and lymphatic system disorders Febrile neutropenia	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Fever	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Vascular disorders Hot flashes	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Hypokalemia	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Lymphocyte count decreased	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Nausea	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Neutrophil count decreased	14.6% 7/48 • Number of events 11 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Peripheral sensory neuropathy	4.2% 2/48 • Number of events 2 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Platelet count decreased	4.2% 2/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Weight loss	4.2% 2/48 • Number of events 2 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations White blood cell decreased	2.1% 1/48 • Number of events 1 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment

Other adverse events

Other adverse events
Measure	FOLFIRINOX + Radiation n=48 participants at risk All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy. FOLFIRINOX: Up to Eight-14 day cycles Capecitabine: Orally, for 10 days Short Course Radiation: Five or ten days Surgery: 1-4 weeks after completion of capecitabine therapy
Gastrointestinal disorders Nausea	95.8% 46/48 • Number of events 217 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Neck pain	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	10.4% 5/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Abdominal distension	37.5% 18/48 • Number of events 38 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Abdominal pain	91.7% 44/48 • Number of events 187 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Alanine aminotransferase increased	41.7% 20/48 • Number of events 43 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Alkaline phosphatase increased	12.5% 6/48 • Number of events 12 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Immune system disorders Allergic reaction	8.3% 4/48 • Number of events 14 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Skin and subcutaneous tissue disorders Alopecia	39.6% 19/48 • Number of events 55 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Blood and lymphatic system disorders Anemia	14.6% 7/48 • Number of events 14 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Anorexia	93.8% 45/48 • Number of events 163 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Psychiatric disorders Anxiety	54.2% 26/48 • Number of events 70 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Arthralgia	20.8% 10/48 • Number of events 17 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Arthritis	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Ascites	12.5% 6/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Aspartate aminotransferase increased	20.8% 10/48 • Number of events 33 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Cardiac disorders Atrial fibrillation	8.3% 4/48 • Number of events 6 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Back pain	56.2% 27/48 • Number of events 72 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Infections and infestations Biliary tract infection	12.5% 6/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Bloating	33.3% 16/48 • Number of events 33 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Blood bilirubin increased	33.3% 16/48 • Number of events 31 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Eye disorders Blurred vision	10.4% 5/48 • Number of events 10 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Bone pain	25.0% 12/48 • Number of events 22 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Injury, poisoning and procedural complications Bruising	20.8% 10/48 • Number of events 15 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Cardiac disorders Cardiac disorders - Other	18.8% 9/48 • Number of events 17 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Chest wall pain	12.5% 6/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Chills	33.3% 16/48 • Number of events 21 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Cholesterol high	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Cognitive disturbance	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Concentration impairment	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Psychiatric disorders Confusion	10.4% 5/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Constipation	83.3% 40/48 • Number of events 114 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Cough	31.2% 15/48 • Number of events 34 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Dehydration	52.1% 25/48 • Number of events 69 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Psychiatric disorders Depression	31.2% 15/48 • Number of events 28 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Diarrhea	89.6% 43/48 • Number of events 201 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Dizziness	50.0% 24/48 • Number of events 55 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Eye disorders Dry eye	6.2% 3/48 • Number of events 6 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Dry mouth	22.9% 11/48 • Number of events 15 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Skin and subcutaneous tissue disorders Dry skin	16.7% 8/48 • Number of events 16 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Dysarthria	10.4% 5/48 • Number of events 9 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Dysesthesia	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Dysgeusia	52.1% 25/48 • Number of events 36 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Dyspepsia	25.0% 12/48 • Number of events 20 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Dysphagia	10.4% 5/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	29.2% 14/48 • Number of events 33 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Edema face	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Edema limbs	37.5% 18/48 • Number of events 51 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Enterocolitis	8.3% 4/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Epistaxis	22.9% 11/48 • Number of events 19 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Eye disorders Eye disorders - Other	14.6% 7/48 • Number of events 11 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Eye disorders Eye pain	6.2% 3/48 • Number of events 6 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Facial pain	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Injury, poisoning and procedural complications Fall	10.4% 5/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Fatigue	100.0% 48/48 • Number of events 258 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Fecal incontinence	10.4% 5/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Fever	58.3% 28/48 • Number of events 44 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Flank pain	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Flatulence	41.7% 20/48 • Number of events 57 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Vascular disorders Flushing	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Gait disturbance	16.7% 8/48 • Number of events 14 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Gastroesophageal reflux disease	35.4% 17/48 • Number of events 28 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Gastrointestinal disorders - Other	54.2% 26/48 • Number of events 54 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Gastroparesis	8.3% 4/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders General disorders and administration site conditions - Other	22.9% 11/48 • Number of events 39 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Generalized muscle weakness	18.8% 9/48 • Number of events 28 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Psychiatric disorders Hallucinations	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Headache	29.2% 14/48 • Number of events 31 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Hemorrhoids	8.3% 4/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Hepatobiliary disorders Hepatobiliary disorders - Other	20.8% 10/48 • Number of events 28 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Hiccups	14.6% 7/48 • Number of events 11 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Hyperglycemia	12.5% 6/48 • Number of events 6 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Skin and subcutaneous tissue disorders Hyperhidrosis	10.4% 5/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Hyperkalemia	10.4% 5/48 • Number of events 6 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Vascular disorders Hypertension	27.1% 13/48 • Number of events 19 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Hypokalemia	41.7% 20/48 • Number of events 92 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Hyponatremia	14.6% 7/48 • Number of events 9 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Vascular disorders Hypotension	33.3% 16/48 • Number of events 26 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Hypoxia	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Infections and infestations Infections and infestations - Other	20.8% 10/48 • Number of events 16 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Psychiatric disorders Insomnia	66.7% 32/48 • Number of events 78 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Lethargy	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Malabsorption	27.1% 13/48 • Number of events 20 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Malaise	14.6% 7/48 • Number of events 13 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Memory impairment	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Infections and infestations Mucosal infection	6.2% 3/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Mucositis oral	41.7% 20/48 • Number of events 36 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	16.7% 8/48 • Number of events 12 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Myalgia	18.8% 9/48 • Number of events 18 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 4/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Nervous system disorders - Other	14.6% 7/48 • Number of events 13 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Neutrophil count decreased	12.5% 6/48 • Number of events 10 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Non-cardiac chest pain	10.4% 5/48 • Number of events 9 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Oral pain	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
General disorders Pain	14.6% 7/48 • Number of events 10 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Musculoskeletal and connective tissue disorders Pain in extremity	22.9% 11/48 • Number of events 18 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Skin and subcutaneous tissue disorders Pain of skin	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	10.4% 5/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Cardiac disorders Palpitations	12.5% 6/48 • Number of events 9 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Pancreatic enzymes decreased	12.5% 6/48 • Number of events 11 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Pancreatitis	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Paresthesia	18.8% 9/48 • Number of events 14 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Peripheral motor neuropathy	8.3% 4/48 • Number of events 6 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Peripheral sensory neuropathy	95.8% 46/48 • Number of events 243 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Platelet count decreased	22.9% 11/48 • Number of events 21 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Pleural effusion	10.4% 5/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Postnasal drip	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Productive cough	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Skin and subcutaneous tissue disorders Pruritus	22.9% 11/48 • Number of events 14 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Rectal pain	6.2% 3/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Renal and urinary disorders Renal and urinary disorders - Other	10.4% 5/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Reproductive system and breast disorders Reproductive system and breast disorders - Other	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	22.9% 11/48 • Number of events 15 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Infections and infestations Sepsis	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Cardiac disorders Sinus tachycardia	14.6% 7/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	47.9% 23/48 • Number of events 51 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Infections and infestations Skin infection	10.4% 5/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Small intestinal obstruction	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Somnolence	6.2% 3/48 • Number of events 3 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Sore throat	18.8% 9/48 • Number of events 18 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Spasticity	16.7% 8/48 • Number of events 19 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Cardiac disorders Supraventricular tachycardia	8.3% 4/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Vascular disorders Thromboembolic event	10.4% 5/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Toothache	6.2% 3/48 • Number of events 4 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Nervous system disorders Tremor	6.2% 3/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Infections and infestations Upper respiratory infection	16.7% 8/48 • Number of events 11 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Renal and urinary disorders Urinary frequency	20.8% 10/48 • Number of events 20 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Renal and urinary disorders Urinary incontinence	8.3% 4/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Infections and infestations Urinary tract infection	14.6% 7/48 • Number of events 16 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Renal and urinary disorders Urinary tract pain	6.2% 3/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Renal and urinary disorders Urinary urgency	10.4% 5/48 • Number of events 6 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Renal and urinary disorders Urine discoloration	16.7% 8/48 • Number of events 12 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Gastrointestinal disorders Vomiting	62.5% 30/48 • Number of events 73 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Eye disorders Watering eyes	6.2% 3/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Weight gain	6.2% 3/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Investigations Weight loss	85.4% 41/48 • Number of events 163 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Respiratory, thoracic and mediastinal disorders Wheezing	8.3% 4/48 • Number of events 8 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Injury, poisoning and procedural complications Wound complication	6.2% 3/48 • Number of events 5 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment
Injury, poisoning and procedural complications Wound dehiscence	8.3% 4/48 • Number of events 7 • From the start of treatment until 30 days after the end of treatment, about 6 months. Treatment is continued until disease progression, intercurrent illness that prevents further treatment, unacceptable adverse events, participant withdrawal, or until the treating investigator decides it is in the participants best interest. Adverse events were defined as any grade 3 or greater toxicity deemed to be possibly, probably, or definitely related to treatment

Additional Information

Dr. Theodore Hong

Massachusetts General Hospital

Phone: 617-726-6050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place