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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT00898287
First received: May 6, 2009
Last updated: January 19, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Drug: P276-00
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • To determine the maximum tolerated dose (MTD) of P276-00 administered along with Gemcitabine. [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate pharmacokinetic parameters of P276-00. [ Time Frame: one week ] [ Designated as safety issue: No ]
  • To determine clinical benefit response to P276-00 in combination with Gemcitabine in patients with cancer of pancreas. [ Time Frame: Every week ] [ Designated as safety issue: No ]
  • To determine objective tumor response rate to P276-00 in combination with Gemcitabine in patients with cancer of pancreas. [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • To characterize toxicities of P276-00 in combination with Gemcitabine. [ Time Frame: Every week ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: May 2009
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: P276-00 plus Gemcitabine

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.

Drug: P276-00
Subjects will be enrolled at different levels of P276-00 dosage as follows:- Level 1 - 100mg/ m 2/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.
Other Name: P276-00
Drug: Gemcitabine
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.
Other Name: Gemcitabine

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00898287

Locations
India
Central India Cancer Research Institute
Nagpur, Ajayonco@hotmail.com, India, 440 010
Global Hospital
Hyderabaad, Andhra Pradesh, India, 500004
Curie Manavata Cancer Centre
Nashik, Maharashtra, India, 422 004
Deenanath Mangeshkar Hospital & Research Centre
Pune, Maharashtra, India, 411004
Sri RamaChandra Medical Centre
Chennai, Tamil Nadu, India, 600 116
Lifeline Mutispecilaity Hospital
Chennai, Tamil Nadu, India, 600096
Meenakshi Mission Hospital & Reasearch Centre
Madurai, Tamil Nadu, India, 625107
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Amol Bapaye, MS Deenanath Mangeshkar Hospital & Research Centre, ,Pune, India
Principal Investigator: Raj Nagarkar, MS Curie Manavata Cancer Centre, Nashik, India
Principal Investigator: J S Rajkumar, DNB Lifeline Mutispecilaity Hospital, Chennai, India
Principal Investigator: Ravi K Saxena, DNB Global Hospital, Hyderabad, India.
Principal Investigator: Kirushna Kumar, MD Meenakshi Mission Hospital & Reasearch Centre, Madurai, India
Principal Investigator: Anita Ramesh, MD Sri RamaChandra Medical Centre, Chennai, India
Principal Investigator: Ajay Mehta, MS Central India cancer Research Institute, Nagpur, India
  More Information

No publications provided

Responsible Party: Piramal Enterprises Limited
ClinicalTrials.gov Identifier: NCT00898287     History of Changes
Other Study ID Numbers: P276-00/28/08, P276-00/28/08
Study First Received: May 6, 2009
Last Updated: January 19, 2012
Health Authority: India: Drugs Controller General of India

Keywords provided by Piramal Enterprises Limited:
Locally advanced or metastatic adenocarcinoma of pancreas

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 17, 2014