A Phase I/II Study to Evaluate Safety and Efficacy of P276-00 in Combination With Gemcitabine in Patients With Cancer of Pancreas
18 Years
N/A
Both
Pancreatic Cancer
Trial Information
A Phase I/II Study to Evaluate Safety and Efficacy of P276-00 in Combination With Gemcitabine in Patients With Cancer of Pancreas
This study is an open label multicenter trial to evaluate safety and efficacy of P276-00 in
combination with Gemcitabine in subjects with locally advanced or metastatic pancreatic
cancer. Primary objective in part A is to determine maximum tolerated dose (MTD) of P276-00
in combination with Gemcitabine and in part B to evaluate efficacy of this combination in
subjects with locally advanced or metastatic pancreatic cancer. In part A, cohort of 3
subjects will be enrolled at starting dose level of P276-00 which is 100 mg/m2/ day to be
given intravenously (IV) from day 1 to day 5 every 21 days. This constitutes one cycle of
P276-00. If this dose is well tolerated then next cohort will be enrolled at higher dose
level of P276-00. P276-00 dose escalation will continue until MTD of P276-00 in combination
with Gemcitabine is determined. The subsequent dose levels of P276-00 will be 140 mg/m2/day
and 185 mg/m2/day. In part B ten subjects will be evaluated at the MTD of P276-00 in
combination with Gemcitabine to evaluate efficacy of the combination. Dose of Gemcitabine
will be same in both parts of the study which is 1000mg/m2 over 30mins every week for 7
weeks followed by a gap of one week and then 3 weekly doses every 4 weeks. Subjects will be
treated for six cycles of P276-00 in combination with Gemcitabine or until evidence of
disease progression or unacceptable toxicity. Safety evaluations will be performed at
regular intervals by means of record of vital parameters, physical examination and
laboratory investigations for hematology and biochemistry. Efficacy assessment will be
performed by means of weekly record of pain intensity, analgesic consumption, change in
weight and performance status for evaluation of clinical benefit response and by means of CT
scans at the end of every 2 cycles for evaluation of tumor response by RECIST (Response
Evaluation Criteria in Solid Tumors)
Inclusion Criteria:
1. Histologically or cytologically confirmed diagnosis of infiltrating ductal
adenocarcinoma of pancreas.
2. Chemonaive patients i.e. patients must not have received chemotherapy or
biologic/targeted anticancer therapy for the adenocarcinoma of pancreas.
3. Locally advanced inoperable pancreatic cancer.
4. Patients of either sex, aged > or = 18 years.
5. Karnofsky performance status of > or = 60%.
6. Adequate bone marrow reserve: white blood cell (WBC) count > or = 4 x 109/l, Absolute
neutrophil count (ANC) ≥ 1.5 x 109/l, platelets > or = 100 x 109/l, hemoglobin > or =
10 g/dl.
7. Adequate liver function: bilirubin < or = 1.5 times the upper normal value, ALT/AST/
alkaline phosphatase less than 3 times the upper normal value (unless due to liver
metastases in which case bilirubin less than 3 times the upper normal value, ALT/AST
less than 4 times the upper normal value, and alkaline phosphatase without limit).
8. Adequate renal function: creatinine ≤ 1.5 times the upper normal value.
9. If female:
- Childbearing potential either terminated by surgery, radiation, or menopause, or
attenuated by use of at least 2 approved contraceptive methods (at least one
should be a barrier method) during and for 4 weeks after stopping the study
treatment.
- Negative urine β-HCG test within 1 week prior to protocol entry where
childbearing potential is not terminated.
10. Additional inclusion criterion only for part B: Patient should satisfy at least one
of the following criteria on cycle 1 day 1:
- Karnofsky performance status of 60 or 70
- Baseline pain intensity score of > or = 20 mm
Exclusion Criteria:
1. Inability / unwillingness to give consent.
2. Pregnant or breast feeding women.
3. Brain metastasis (active or inactive).
4. Serious concomitant systemic disorders incompatible with the study (at the discretion
of the investigator).
5. Patients known to be suffering from infection with HIV, Hepatitis C or Hepatitis B.
6. Patients who had received any other investigational drug within 1 month prior to Day
1 of protocol treatment.
7. Patients with QTc > 450 msec on 12-lead standard electrocardiogram (ECG).
8. Major surgery within 2 weeks prior to protocol treatment.
9. Radiotherapy to > 10% of bone marrow.
10. Patients with 3rd space fluid accumulation (ascites, pleural effusion).
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the maximum tolerated dose (MTD) of P276-00 administered along with Gemcitabine.
Outcome Time Frame:
3 weeks
Safety Issue:
Yes
Principal Investigator
Amol Bapaye, MS
Investigator Role:
Principal Investigator
Investigator Affiliation:
Deenanath Mangeshkar Hospital & Research Centre, ,Pune, India
Authority:
India: Drugs Controller General of India
Study ID:
P276-00/28/08
NCT ID:
NCT00898287
Start Date:
May 2009
Completion Date:
Related Keywords:
- Pancreatic Cancer
- Locally advanced or metastatic adenocarcinoma of pancreas
- Pancreatic Neoplasms
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