A clinical trial to study safety and effects of P276-00 in combination with Gemcitabine in treatment of pancreatic cancer .

Phase 1/2

Completed

• Conditions: Newly diagnosed inoperable locally advanced or metastatic infiltrating ductal adenocarcinoma of pancreas.

• Registration Number: CTRI/2009/091/000214
• Lead Sponsor: Piramal Life Sciences Limited

Brief Summary

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 till MTD of P276-00 in combination with Gemcitabine is determined. In part B ten subjects will be evaluated at this MTD of P276-00 in combination with Gemcitabine to evaluate for efficacy. 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)

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01-06
• Last Update Posted: 2014-07-17

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 23

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of infiltrating ductal adenocarcinoma of pancreas.
• 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.
• Patients of either sex, aged > or = 18 years.5. Karnofsky performance status of > or = 60%.
• Adequate bone marrow reserve: white blood cell (WBC) count > or = 4 x 109/l, Absolute neutrophil count (ANC) > or = 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).
• Adequate renal function: creatinine < or = 1.5 times the upper normal value.9. If female a)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.
• b) Negative urine beta 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:a) Karnofsky performance status of 60 or 70 b)Baseline analgesic consumption of > or = 10 morphine equivalent per day c) Baseline pain intensity score of > or = 20 mm.

Exclusion Criteria

• Inability / unwillingness to give consent 2.
• Pregnant or breast feeding women 3.
• Brain metastasis (active or inactive) 4.
• Serious concomitant systemic disorders including, but not limited to active infection, congestive heart failure, cardiac arrhythmia, psychiatric illness etc that are incompatible with the study (at the discretion of the investigator) 5.Patients known to be suffering from infection with HIV,Tuberculosis,Hepatitis C or Hepatitis B.
• Patients who had received any other investigational drug within 1 month prior to Day 1 of protocol treatment or who have not recovered (to grade 1) from adverse effects of the investigational agent received prior to this period.
• 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 clinically significant 3rd space fluid 1.accumulation (ascites, pleural effusion).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine clinical benefit response to P276-00 in combination with Gemcitabine in patients with cancer of pancreas.	At the end of study

Secondary Outcome Measures

Name	Time	Method
To evaluate pharmacokinetic parameters of P276-00.	At the end of study
To evaluate exploratory biomarkers associated with use of P276-00 and Gemcitabine.	At the end of study
To characterize toxicities of P276-00 in combination with Gemcitabine.	At the end of study

Trial Locations

Locations (7)

Global Hospital, Lakdi-Ka-Pool, Hyderabad-500004, India.; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

Curie Manavata Cancer Centre, Opp. Mahamarya Bus Stand, Mumbai Naka, Nashik- 422 004, Maharashtra; 🇮🇳 Nashik, MAHARASHTRA, India

Deenanath Mangeshkar Hospital & Research Centre,Erandwane,Pune-411004; 🇮🇳 Pune, MAHARASHTRA, India

entral India Cancer Research Institute, 11, Shankar Nagar, West High Court Road, Nagpur - 440 010; 🇮🇳 Nagpur, MAHARASHTRA, India

Lifeline Mutispecilaity Hospital, Perungudi Chennai - 600096; 🇮🇳 Chennai, TAMIL NADU, India

Meenakshi Mission Hospital & Reasearch Centre. Lake Area. Melur. Madurai-625107; 🇮🇳 Madurai, TAMIL NADU, India

Sri RamaChandra Medical Centre, No1, Ramachandra Nagar, Porur, Chennai- 600 116; 🇮🇳 Chennai, TAMIL NADU, India

Global Hospital, Lakdi-Ka-Pool, Hyderabad-500004, India.

🇮🇳Hyderabad, ANDHRA PRADESH, India

Dr. Ravi Kumar Saxena

Principal investigator

9949385000