Back to results

Safety and Efficacy Study of P276-00 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer (SAVIOR)

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 1

Locations

India

Study Type

Interventional

Intervention

P276-00

Gemcitabine

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring Locally advanced or metastatic adenocarcinoma of pancreas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.
Locally advanced inoperable pancreatic cancer.
Patients of either sex, aged > or = 18 years.
Karnofsky performance status of > or = 60%.
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.
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 ≤ 1.5 times the upper normal value.
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.
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:

Inability / unwillingness to give consent.
Pregnant or breast feeding women.
Brain metastasis (active or inactive).
Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
Patients known to be suffering from infection with HIV, Hepatitis C or Hepatitis B.
Patients who had received any other investigational drug within 1 month prior to Day 1 of protocol treatment.
Patients with QTc > 450 msec on 12-lead standard electrocardiogram (ECG).
Major surgery within 2 weeks prior to protocol treatment.
Radiotherapy to > 10% of bone marrow.
Patients with 3rd space fluid accumulation (ascites, pleural effusion).

Sites / Locations

Central India Cancer Research Institute
Global Hospital
Curie Manavata Cancer Centre
Deenanath Mangeshkar Hospital & Research Centre
Sri RamaChandra Medical Centre
Lifeline Mutispecilaity Hospital
Meenakshi Mission Hospital & Reasearch Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

P276-00 plus Gemcitabine

Arm Description

Subjects will be enrolled at different levels of P276-00 dosage as follows:- Level 1 - 100mg/m2/day x 5 q 3 weeks Level 2 - 140 mg/m2/day x 5 q 3 weeks Level 3 - 185 mg/m2/day x 5 q 3 weeks P276-00 will be administered as intravenous infusion in 200 ml of 5% dextrose over 30min from days 1 to 5 per 21 day cycle. Six such cycles will be administered unless there is progression of disease or unacceptable toxicity. Gemcitabine will be administered as an intravenous infusion at dose of 1000mg/m2 over 30 mins every week for 7 weeks followed by a gap of one week and then 3 weekly doses every 4 weeks. This treatment will be continued for six P276-00 cycles of 3 weeks each unless there is progression of disease or unacceptable toxicity.

Outcomes

Primary Outcome Measures

To determine the maximum tolerated dose (MTD) of P276-00 administered along with Gemcitabine.

Secondary Outcome Measures

To evaluate pharmacokinetic parameters of P276-00.

To determine clinical benefit response to P276-00 in combination with Gemcitabine in patients with cancer of pancreas.

To determine objective tumor response rate to P276-00 in combination with Gemcitabine in patients with cancer of pancreas.

To characterize toxicities of P276-00 in combination with Gemcitabine.

Full Information

NCT ID

NCT00898287

First Posted

May 6, 2009

Last Updated

January 19, 2012

Sponsor

Piramal Enterprises Limited

1. Study Identification

Unique Protocol Identification Number

NCT00898287

Brief Title

Safety and Efficacy Study of P276-00 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer

Acronym

SAVIOR

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

2. Study Status

Record Verification Date

January 2012

Overall Recruitment Status

Completed

Study Start Date

May 2009 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Piramal Enterprises Limited

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer

Keywords

Locally advanced or metastatic adenocarcinoma of pancreas

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

P276-00 plus Gemcitabine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

P276-00

Intervention Description

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

Gemcitabine will be administered as an intravenous infusion at dose of 1000mg/m 2 over 30 mins every week for 7 weeks followed by a gap of one week and then 3 weekly doses every 4 weeks. This treatment will be continued for six P276-00 cycles of 3 weeks each unless there is progression of disease or unacceptable toxicity.

Primary Outcome Measure Information:

Title

To determine the maximum tolerated dose (MTD) of P276-00 administered along with Gemcitabine.

Time Frame

3 weeks

Secondary Outcome Measure Information:

Title

To evaluate pharmacokinetic parameters of P276-00.

Time Frame

one week

Title

To determine clinical benefit response to P276-00 in combination with Gemcitabine in patients with cancer of pancreas.

Time Frame

Every week

Title

To determine objective tumor response rate to P276-00 in combination with Gemcitabine in patients with cancer of pancreas.

Time Frame

Every 6 weeks

Title

To characterize toxicities of P276-00 in combination with Gemcitabine.

Time Frame

Every week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. Locally advanced inoperable pancreatic cancer. Patients of either sex, aged > or = 18 years. Karnofsky performance status of > or = 60%. 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. 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 ≤ 1.5 times the upper normal value. 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. 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: Inability / unwillingness to give consent. Pregnant or breast feeding women. Brain metastasis (active or inactive). Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator). Patients known to be suffering from infection with HIV, Hepatitis C or Hepatitis B. Patients who had received any other investigational drug within 1 month prior to Day 1 of protocol treatment. Patients with QTc > 450 msec on 12-lead standard electrocardiogram (ECG). Major surgery within 2 weeks prior to protocol treatment. Radiotherapy to > 10% of bone marrow. Patients with 3rd space fluid accumulation (ascites, pleural effusion).

Overall Study Officials: