Trial Outcomes & Findings for A Study of Combination of Gemcitabine, Oxaliplatin (GEMOX)-Sorafenib in Patients With Advanced Biliary Tract Cancer (NCT NCT00955721)
NCT ID: NCT00955721
Last Updated: 2018-01-03
Results Overview
Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
9 participants
Primary outcome timeframe
First two 14-day Phase I cycles
Results posted on
2018-01-03
Participant Flow
Participant milestones
| Measure |
Phase 1: GEMOX + Sorafenib
Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
Phase 2: RPTD GEMOX + Sorafenib
Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
0
|
|
Overall Study
COMPLETED
|
6
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
0
|
Reasons for withdrawal
| Measure |
Phase 1: GEMOX + Sorafenib
Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
Phase 2: RPTD GEMOX + Sorafenib
Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
A Study of Combination of Gemcitabine, Oxaliplatin (GEMOX)-Sorafenib in Patients With Advanced Biliary Tract Cancer
Baseline characteristics by cohort
| Measure |
Phase 1: GEMOX + Sorafenib
n=9 Participants
Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
Phase 2: RPTD GEMOX + Sorafenib
Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
—
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
—
|
7 Participants
n=5 Participants
|
|
Age, Continuous
|
67.4 years
n=5 Participants
|
—
|
67.4 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
—
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
—
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
—
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First two 14-day Phase I cyclesPopulation: A total of 9 participants were enrolled in Phase 1 of which 6 were evaluable and analyzed for this outcome measure. A recommended phase two dose (RPTD) of the combination of Sorafenib and GEMOX therapy could not be determined because dose escalation was still in progress when the study was terminated.
Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).
Outcome measures
| Measure |
Phase 1: GEMOX + Sorafenib
n=6 Participants
Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib.
* Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
Gemcitabine: Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
Oxaliplatin: Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
Sorafenib: Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
|---|---|
|
Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC).
Gemcitabine
|
NA mg
A recommended phase two dose (RPTD) of the combination of Sorafenib and GEMOX therapy could not be determined because dose escalation was still in progress when the study was terminated.
|
|
Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC).
Oxaliplatin
|
NA mg
A recommended phase two dose (RPTD) of the combination of Sorafenib and GEMOX therapy could not be determined because dose escalation was still in progress when the study was terminated.
|
|
Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC).
Sorafenib
|
NA mg
A recommended phase two dose (RPTD) of the combination of Sorafenib and GEMOX therapy could not be determined because dose escalation was still in progress when the study was terminated.
|
PRIMARY outcome
Timeframe: 9 MonthsPopulation: This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the determination of the RPTD and the opening of Phase 2.
Rate of study participants achieving progression-free survival at 9 months post-initiation of study therapy at RPTD. Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: About 9 MonthsPopulation: This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
Overall response rate \[CR + PR\]. Clinical Benefit Rate \[Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)\] per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Start of treatment until death or date of last contactPopulation: This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
Overall survival is defined as the time elapsed from the start of treatment until death. For surviving patients, follow-up will be censored at the date of last contact.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: About 9 MonthsPopulation: This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
Rate of study participants experiencing toxicity after receiving study therapy at the recommended Phase 2 Dose (RPTD).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 MonthsPopulation: This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
A study of the correlation between biomarker levels and response to RPTD study therapy. Blood samples for biomarker analysis are collected at baseline and on day 1 of Cycles 2 onward
Outcome measures
Outcome data not reported
Adverse Events
Phase 1: GEMOX + Sorafenib
Serious events: 3 serious events
Other events: 8 other events
Deaths: 4 deaths
Phase 2: RPTD GEMOX + Sorafenib
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: GEMOX + Sorafenib
n=9 participants at risk
Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
Phase 2: RPTD GEMOX + Sorafenib
Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Infections and infestations
Peritoneal Infection
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Gastrointestinal disorders
Dehydration
|
22.2%
2/9 • Number of events 2
|
—
0/0
|
|
Gastrointestinal disorders
Diarrhea
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Nervous system disorders
Dizziness
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
General disorders
Fever
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Cardiac disorders
Hypotension
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
Other adverse events
| Measure |
Phase 1: GEMOX + Sorafenib
n=9 participants at risk
Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
Phase 2: RPTD GEMOX + Sorafenib
Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
44.4%
4/9 • Number of events 6
|
—
0/0
|
|
Vascular disorders
Vaginal Hemorrhage
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Renal and urinary disorders
Urine Discoloration
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
General disorders
Toothache
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Gastrointestinal disorders
Taste Alteration
|
22.2%
2/9 • Number of events 2
|
—
0/0
|
|
Cardiac disorders
Supraventricular tachycardia
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Vascular disorders
Rectal hemorrhage
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.2%
2/9 • Number of events 3
|
—
0/0
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
3/9 • Number of events 6
|
—
0/0
|
|
Gastrointestinal disorders
Abdominal Pain
|
55.6%
5/9 • Number of events 13
|
—
0/0
|
|
Metabolism and nutrition disorders
Alanine aminotransferase increased
|
55.6%
5/9 • Number of events 17
|
—
0/0
|
|
Metabolism and nutrition disorders
Alkaline phosphatase increased
|
66.7%
6/9 • Number of events 14
|
—
0/0
|
|
Metabolism and nutrition disorders
Aspartate aminotransferase increased
|
77.8%
7/9 • Number of events 18
|
—
0/0
|
|
Skin and subcutaneous tissue disorders
Acne
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Gastrointestinal disorders
Abdominal Distention
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Immune system disorders
Allergic Reaction
|
22.2%
2/9 • Number of events 2
|
—
0/0
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Gastrointestinal disorders
Anorexia
|
66.7%
6/9 • Number of events 13
|
—
0/0
|
|
Nervous system disorders
Anxiety
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Gastrointestinal disorders
Ascites
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
General disorders
Back Pain
|
44.4%
4/9 • Number of events 6
|
—
0/0
|
|
Cardiac disorders
Cardiac ischemia/infarction
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
General disorders
Chest Pain
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Gastrointestinal disorders
Constipation
|
22.2%
2/9 • Number of events 4
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.2%
2/9 • Number of events 3
|
—
0/0
|
|
Nervous system disorders
Depression
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
General disorders
Death - Disease Progression
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Ear, nose and throat examination abnormal
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Blood and lymphatic system disorders
Edema limbs
|
33.3%
3/9 • Number of events 3
|
—
0/0
|
|
General disorders
Fatigue
|
77.8%
7/9 • Number of events 14
|
—
0/0
|
|
General disorders
Fever
|
22.2%
2/9 • Number of events 4
|
—
0/0
|
|
Gastrointestinal disorders
Flatulence
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Gastrointestinal disorders
Gastritis
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Gastrointestinal disorders
GI - Other
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome
|
33.3%
3/9 • Number of events 3
|
—
0/0
|
|
General disorders
Headache
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Ear and labyrinth disorders
Hearing (monitoring program)
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Blood and lymphatic system disorders
Hemoglobin
|
88.9%
8/9 • Number of events 24
|
—
0/0
|
|
Metabolism and nutrition disorders
Hyperbilirubinemia
|
22.2%
2/9 • Number of events 4
|
—
0/0
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
55.6%
5/9 • Number of events 11
|
—
0/0
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
33.3%
3/9 • Number of events 3
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
22.2%
2/9 • Number of events 5
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypernatremia
|
11.1%
1/9 • Number of events 3
|
—
0/0
|
|
Cardiac disorders
Hypertension
|
33.3%
3/9 • Number of events 5
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
77.8%
7/9 • Number of events 19
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
22.2%
2/9 • Number of events 8
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
22.2%
2/9 • Number of events 3
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypokalemia
|
22.2%
2/9 • Number of events 5
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Metabolism and nutrition disorders
Hyponatremia
|
33.3%
3/9 • Number of events 4
|
—
0/0
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
44.4%
4/9 • Number of events 10
|
—
0/0
|
|
Endocrine disorders
Hypothyroidism
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
General disorders
Joint Pain
|
22.2%
2/9 • Number of events 2
|
—
0/0
|
|
Blood and lymphatic system disorders
Leukocytes
|
66.7%
6/9 • Number of events 21
|
—
0/0
|
|
Hepatobiliary disorders
Liver dysfunction
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Blood and lymphatic system disorders
Lymphopenia
|
55.6%
5/9 • Number of events 11
|
—
0/0
|
|
Gastrointestinal disorders
Mucositis oral
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
Gastrointestinal disorders
Nausea
|
44.4%
4/9 • Number of events 9
|
—
0/0
|
|
Blood and lymphatic system disorders
Neutrophils
|
22.2%
2/9 • Number of events 8
|
—
0/0
|
|
General disorders
Pain
|
11.1%
1/9 • Number of events 2
|
—
0/0
|
|
General disorders
Pain - Other
|
33.3%
3/9 • Number of events 4
|
—
0/0
|
|
Cardiac disorders
Palpitations
|
11.1%
1/9 • Number of events 1
|
—
0/0
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
44.4%
4/9 • Number of events 14
|
—
0/0
|
|
General disorders
Pharyngolaryngeal pain
|
22.2%
2/9 • Number of events 3
|
—
0/0
|
|
Blood and lymphatic system disorders
Platelets
|
66.7%
6/9 • Number of events 16
|
—
0/0
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place