Clinical trial NCT00898287: Safety and Efficacy Study of P276-00 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
Official title: A Phase I/II Study to Evaluate Safety and Efficacy of P276-00 in Combination With Gemcitabine in Patients With Cancer of Pancreas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: Locally advanced or metastatic adenocarcinoma of pancreas
Lead sponsor: Piramal Enterprises Limited
Sponsor class: INDUSTRY
First posted: 2009-05-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to identify a dose of P276-00 that can be safely administered along with Gemcitabine and to examine safety and efficacy of the combination in treatment of advanced pancreatic cancer.

Detailed description: 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)

Eligibility criteria: 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).

Primary outcomes:
measure: To determine the maximum tolerated dose (MTD) of P276-00 administered along with Gemcitabine.
timeFrame: 3 weeks
Secondary outcomes:
measure: To evaluate pharmacokinetic parameters of P276-00.
timeFrame: one week
measure: To determine clinical benefit response to P276-00 in combination with Gemcitabine in patients with cancer of pancreas.
timeFrame: Every week
measure: To determine objective tumor response rate to P276-00 in combination with Gemcitabine in patients with cancer of pancreas.
timeFrame: Every 6 weeks
measure: To characterize toxicities of P276-00 in combination with Gemcitabine.
timeFrame: Every week
Other outcomes:
Locations:
city: Nagpur
country: India
facility: Central India Cancer Research Institute
state: Ajayonco@hotmail.com
city: Hyderabaad
country: India
facility: Global Hospital
state: Andhra Pradesh
city: Nashik
country: India
facility: Curie Manavata Cancer Centre
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Maharashtra
city: Chennai
country: India
facility: Sri RamaChandra Medical Centre
state: Tamil Nadu
city: Chennai
country: India
facility: Lifeline Mutispecilaity Hospital
state: Tamil Nadu
city: Madurai
country: India
facility: Meenakshi Mission Hospital & Reasearch Centre
state: Tamil Nadu
Study officials:
affiliation: Deenanath Mangeshkar Hospital & Research Centre, ,Pune, India
name: Amol Bapaye, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Curie Manavata Cancer Centre, Nashik, India
name: Raj Nagarkar, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Lifeline Mutispecilaity Hospital, Chennai, India
name: J S Rajkumar, DNB
role: PRINCIPAL_INVESTIGATOR
affiliation: Global Hospital, Hyderabad, India.
name: Ravi K Saxena, DNB
role: PRINCIPAL_INVESTIGATOR
affiliation: Meenakshi Mission Hospital & Reasearch Centre, Madurai, India
name: Kirushna Kumar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sri RamaChandra Medical Centre, Chennai, India
name: Anita Ramesh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Central India cancer Research Institute, Nagpur, India
name: Ajay Mehta, MS
role: PRINCIPAL_INVESTIGATOR
References: