Trial Outcomes & Findings for Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma (NCT NCT04088188)
NCT ID: NCT04088188
Last Updated: 2024-05-06
Results Overview
A significant toxicity is defined as a Dose Limiting Toxicity that is possibly, probably, or definitely related to treatment. DLTs will be evaluated starting in the first cycle of combination treatment and up to 3 weeks of combination treatment. Toxicities will be assessed using the CTEP Active Version of the CTCAE. All patients meeting the eligibility criteria who have signed a consent form and have begun combination treatment will be considered evaluable for significant toxicity. Patients, who do not experience a DLT but withdraw from protocol therapy prior to 3 weeks, will not be evaluable for the primary endpoint. Incidence of significant toxicity at 3 weeks will be estimated separately by arm and will be defined as the number of patients with significant toxicity within 3 weeks of combination treatment divided by the total number of evaluable patients.
TERMINATED
PHASE1
8 participants
3 weeks
2024-05-06
Participant Flow
Participant milestones
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Cisplatin, Gemcitabine)
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
1
|
|
Overall Study
COMPLETED
|
2
|
1
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Cisplatin, Gemcitabine)
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Adverse Event
|
2
|
0
|
Baseline Characteristics
Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma
Baseline characteristics by cohort
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine) and Arm B (Pemigatinib, Cisplatin, Gemcitabine)
n=7 Participants
Arm A patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
54.7 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Primary Tumor Site
Extrahepatic bile duct
|
1 Participants
n=5 Participants
|
|
Primary Tumor Site
Intrahepatic bile ducts
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 weeksPopulation: Only patients that completed cycle 1 treatment per protocol were evaluated.
A significant toxicity is defined as a Dose Limiting Toxicity that is possibly, probably, or definitely related to treatment. DLTs will be evaluated starting in the first cycle of combination treatment and up to 3 weeks of combination treatment. Toxicities will be assessed using the CTEP Active Version of the CTCAE. All patients meeting the eligibility criteria who have signed a consent form and have begun combination treatment will be considered evaluable for significant toxicity. Patients, who do not experience a DLT but withdraw from protocol therapy prior to 3 weeks, will not be evaluable for the primary endpoint. Incidence of significant toxicity at 3 weeks will be estimated separately by arm and will be defined as the number of patients with significant toxicity within 3 weeks of combination treatment divided by the total number of evaluable patients.
Outcome measures
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=2 Participants
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Gemcitabine, Cisplatin)
n=1 Participants
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Number of Participants With Significant Toxicities
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 27 monthsOverall survival is defined to be the length of time from start of study therapy to death due to any cause. All patients meeting the eligibility criteria that have signed a consent form and begun treatment will be considered evaluable for estimation of the survival distribution. The distribution of overall survival for both arms of the study will be estimated separately using the Kaplan-Meier method.
Outcome measures
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=6 Participants
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Gemcitabine, Cisplatin)
n=1 Participants
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Survival
|
22.9 Months
Interval 18.2 to
Upper CI was not met due to a lack of events.
|
NA Months
The median and CI were not able to be computed due to a lack of events.
|
SECONDARY outcome
Timeframe: 24 monthsProgression free survival time is defined as the time from the start of study therapy to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death. Patients who are still alive and have not progressed will be censored for progression at the time of the last disease evaluation. The time-to-progression distribution will be estimated separately for both arms, using the Kaplan-Meier method.
Outcome measures
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=6 Participants
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Gemcitabine, Cisplatin)
n=1 Participants
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Progression Free Survival
|
15.4 Months
Interval 13.8 to
Upper CI was not reached due to a lack of events.
|
4.9 Months
The CI was unable to be estimated due to a lack of events.
|
SECONDARY outcome
Timeframe: 16 monthsThe number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Outcome measures
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=6 Participants
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Gemcitabine, Cisplatin)
n=1 Participants
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Number of Patients Experiencing Adverse Events
|
5 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 16 monthsThe term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Outcome measures
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=6 Participants
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Gemcitabine, Cisplatin)
n=1 Participants
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Number of Participants Experiencing Toxicities
|
4 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 15 monthsBest Response is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response Evaluation Criteria in Solid Tumors 1.1 criteria will be used for tumor evaluation and patients will be re-evaluated every prior to treatment in cycle 3 and then in odd subsequent cycles. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
Outcome measures
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=6 Participants
Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Gemcitabine, Cisplatin)
n=1 Participants
Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Best Response
PR
|
1 Participants
|
0 Participants
|
|
Best Response
SD
|
5 Participants
|
1 Participants
|
Adverse Events
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
Arm B (Pemigatinib, Cisplatin, Gemcitabine)
Serious adverse events
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=6 participants at risk
Arm A patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Cisplatin, Gemcitabine)
n=1 participants at risk
Arm B patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic, mediastinal - Oth spec
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
Other adverse events
| Measure |
Arm A (Ivosidenib, Cisplatin, Gemcitabine)
n=6 participants at risk
Arm A patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Arm B (Pemigatinib, Cisplatin, Gemcitabine)
n=1 participants at risk
Arm B patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
83.3%
5/6 • Number of events 65 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Ear and labyrinth disorders
Tinnitus
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
Eye disorders
Blurred vision
|
0.00%
0/6 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Eye disorders
Dry eye
|
0.00%
0/6 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Eye disorders
Eye pain
|
0.00%
0/6 • 27 months
|
100.0%
1/1 • Number of events 2 • 27 months
|
|
Gastrointestinal disorders
Constipation
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
3/6 • Number of events 5 • 27 months
|
0.00%
0/1 • 27 months
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/6 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Gastrointestinal disorders
Mucositis oral
|
33.3%
2/6 • Number of events 6 • 27 months
|
0.00%
0/1 • 27 months
|
|
Gastrointestinal disorders
Nausea
|
100.0%
6/6 • Number of events 25 • 27 months
|
100.0%
1/1 • Number of events 3 • 27 months
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6 • Number of events 3 • 27 months
|
0.00%
0/1 • 27 months
|
|
General disorders
Edema face
|
16.7%
1/6 • Number of events 2 • 27 months
|
0.00%
0/1 • 27 months
|
|
General disorders
Edema limbs
|
16.7%
1/6 • Number of events 3 • 27 months
|
100.0%
1/1 • Number of events 3 • 27 months
|
|
General disorders
Fatigue
|
100.0%
6/6 • Number of events 53 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
General disorders
Fever
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
General disorders
Pain
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
Injury, poisoning and procedural complications
Bruising
|
16.7%
1/6 • Number of events 3 • 27 months
|
0.00%
0/1 • 27 months
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
Investigations
Alanine aminotransferase increased
|
16.7%
1/6 • Number of events 2 • 27 months
|
100.0%
1/1 • Number of events 2 • 27 months
|
|
Investigations
Alkaline phosphatase increased
|
66.7%
4/6 • Number of events 20 • 27 months
|
0.00%
0/1 • 27 months
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • Number of events 2 • 27 months
|
0.00%
0/1 • 27 months
|
|
Investigations
Creatinine increased
|
33.3%
2/6 • Number of events 6 • 27 months
|
0.00%
0/1 • 27 months
|
|
Investigations
Lymphocyte count decreased
|
50.0%
3/6 • Number of events 7 • 27 months
|
0.00%
0/1 • 27 months
|
|
Investigations
Neutrophil count decreased
|
66.7%
4/6 • Number of events 20 • 27 months
|
100.0%
1/1 • Number of events 2 • 27 months
|
|
Investigations
Platelet count decreased
|
83.3%
5/6 • Number of events 34 • 27 months
|
100.0%
1/1 • Number of events 3 • 27 months
|
|
Investigations
White blood cell decreased
|
66.7%
4/6 • Number of events 21 • 27 months
|
100.0%
1/1 • Number of events 3 • 27 months
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
1/6 • Number of events 10 • 27 months
|
0.00%
0/1 • 27 months
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
33.3%
2/6 • Number of events 6 • 27 months
|
100.0%
1/1 • Number of events 3 • 27 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
66.7%
4/6 • Number of events 8 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/6 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
33.3%
2/6 • Number of events 31 • 27 months
|
0.00%
0/1 • 27 months
|
|
Psychiatric disorders
Confusion
|
16.7%
1/6 • Number of events 2 • 27 months
|
0.00%
0/1 • 27 months
|
|
Psychiatric disorders
Insomnia
|
33.3%
2/6 • Number of events 8 • 27 months
|
0.00%
0/1 • 27 months
|
|
Renal and urinary disorders
Chronic kidney disease
|
16.7%
1/6 • Number of events 12 • 27 months
|
0.00%
0/1 • 27 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
1/6 • Number of events 5 • 27 months
|
100.0%
1/1 • Number of events 1 • 27 months
|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic, mediastinal - Oth spec
|
33.3%
2/6 • Number of events 5 • 27 months
|
0.00%
0/1 • 27 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
33.3%
2/6 • Number of events 17 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
16.7%
1/6 • Number of events 1 • 27 months
|
0.00%
0/1 • 27 months
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
0.00%
0/6 • 27 months
|
100.0%
1/1 • Number of events 4 • 27 months
|
|
Vascular disorders
Flushing
|
16.7%
1/6 • Number of events 2 • 27 months
|
0.00%
0/1 • 27 months
|
|
Vascular disorders
Hypertension
|
33.3%
2/6 • Number of events 3 • 27 months
|
0.00%
0/1 • 27 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place