Trial Outcomes & Findings for Phase II Capecitabine, Oxaliplatin & Bevacizumab for Metastatic / Unresectable Neuroendocrine Tumors (NCT NCT00398320)

Last Updated: 2017-03-01

Results Overview

Percentage of participants with 12-month progression-free survival (PFS) was assessed. PFS is defined as the time from enrollment until documented disease progression or death (whichever occurred first). RECIST criteria (version 1). Complete response (CR) defined as disappearance of all target lesions. Partial Response (PR) defined as ≥ 30% decrease of SLD. Progressive disease (PD) defined as ≥ 20% increase in Sum Longest Diameters (SLD). Stable Disease (SD) defined as being between 20% increase and \< 30% decrease in SLD.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

PFS assessed every 3 months through 12 months

Results posted on

2017-03-01

Participant Flow

Patients were enrolled at one site in the US over a three-year period.

Participant milestones

Participant milestones
Measure	Capecitabine / Oxaliplatin / Bevacizumab Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle Adverse events (AEs) reported are related and grade 3 or higher per CTCAE version 3.
Overall Study STARTED	40
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Capecitabine / Oxaliplatin / Bevacizumab Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle Adverse events (AEs) reported are related and grade 3 or higher per CTCAE version 3.
Overall Study Death	1
Overall Study Adverse Event	4
Overall Study Physician Decision	1

Baseline Characteristics

Phase II Capecitabine, Oxaliplatin & Bevacizumab for Metastatic / Unresectable Neuroendocrine Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=40 Participants Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
Age, Continuous	55 years n=5 Participants
Gender Female	18 Participants n=5 Participants
Gender Male	22 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants

PRIMARY outcome

Timeframe: PFS assessed every 3 months through 12 months

Outcome measures

Outcome measures
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=40 Participants Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
12-month Progression Free Survival (PFS)	64.7 percentage of participants w/ 12 mo PFS

PRIMARY outcome

Timeframe: 30 days after last treatment

Participants were monitored every 3 weeks while on study. Toxicity and attributions were as per CTCAE version 3.0 guidelines. Analysis population below is patient who experienced related Grade 3 or higher AE; denominator is 40 total patients enrolled.

Outcome measures

Outcome measures
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=40 Participants Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
Number of Patients Who Experienced Treatment-related Grade 3 or Higher Adverse Events by CTCAE Version 3.0	28 participants

SECONDARY outcome

Timeframe: Response rates by RECIST criteria assessed every 3 months while on treatment

Response rate is defined as percent of patients with complete response (CR) and partial response (PR) as their best response as defined by RECIST criteria (version 1). Complete response (CR) is defined as disappearance of all target lesions. Partial Response (PR) is defined as ≥ 30 decrease in the sum of longest diameters of target lesions (SLD). Overall response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=40 Participants Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
Response Rates	17.5 percentage of participants

SECONDARY outcome

Timeframe: Continuous

OS is defined as time from enrollment until death from any cause.

Outcome measures

Outcome measures
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=40 Participants Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
Overall Survival (OS)	42.2 months Interval 0.6 to 60.8

SECONDARY outcome

Timeframe: Assessed every 3 weeks while on treatment

Population: 18 of 40 patients had elevated baseline hormone markers, including Chromogranin A, Gastrin, Glucagon, Pancreatic Polypeptide, vasoactive intestinal peptide (VIP), Urine 5HIAA

Outcome measures

Outcome measures
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=18 Participants Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
Biochemical Markers 25 to 49% reduction in 1 or more hormones	6 participants
Biochemical Markers ≥ 50% reduction in 1 or more hormones	12 participants

Adverse Events

Capecitabine / Oxaliplatin / Bevacizumab

Serious events: 14 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=40 participants at risk Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
Respiratory, thoracic and mediastinal disorders Thrombosis/Embolism	5.0% 2/40 • Number of events 2 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Nervous system disorders Syncope	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Metabolism and nutrition disorders Hypokalemia	7.5% 3/40 • Number of events 3 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
General disorders Death	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Nervous system disorders Confusion	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Surgical and medical procedures Wound dehiscence	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Nervous system disorders Right tongue numbness/deviation	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
General disorders Weight loss	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
General disorders Anorexia	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Blood and lymphatic system disorders Thrombocytopenia	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
General disorders Fatigue	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Dehydration	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Hemorrhage, GI	2.5% 1/40 • Number of events 1 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.

Other adverse events

Other adverse events
Measure	Capecitabine / Oxaliplatin / Bevacizumab n=40 participants at risk Oxaliplatin: 130 mg/m2 intravenously on day 1 of a 21-day cycle Capecitabine: 850 mg/m2 by mouth twice a day for days 1 to 14 on a 21-day cycle Bevacizumab: 7.5mg/kg intravenously on day 1 of a 21-day cycle AEs reported are related and grade 3 or higher per CTCAE version 3.
Ear and labyrinth disorders Tinnitus	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Blood and lymphatic system disorders Low hemoglobin	5.0% 2/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Blood and lymphatic system disorders Low leukocytes	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Blood and lymphatic system disorders Low neutrophils	5.0% 2/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Cardiac disorders Hypertension	12.5% 5/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Skin and subcutaneous tissue disorders Hand foot skin reaction	10.0% 4/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Dehydration	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Diarrhea	20.0% 8/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Nausea	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Bowel obstruction	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Vomiting	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Hemorrhage, GI Upper	5.0% 2/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Metabolism and nutrition disorders Elevated Alk Phos	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Metabolism and nutrition disorders Hyperbilirubinemia	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Metabolism and nutrition disorders Proteinuria	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Metabolism and nutrition disorders Hyponatremia	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Nervous system disorders Sensory neuropathy	7.5% 3/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Gastrointestinal disorders Abdominal pain	5.0% 2/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.
Nervous system disorders Headache	2.5% 1/40 • AEs were collected approximately every 3 weeks when patients were seen by treating MD while they were on active treatment. If a subject experiences more than one of a given AE, the subject is counted only once for that AE.

Additional Information

Pamela L Kunz, MD

Stanford University School of Medicine

Phone: 650-725-8738

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place