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Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Genentech, Inc.
Information provided by (Responsible Party):
Peter C. Enzinger, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00394433
First received: October 31, 2006
Last updated: July 5, 2017
Last verified: July 2017
  Purpose
The purpose of this research study is to determine if the combination of docetaxel, cisplatin, irinotecan and bevacizumab will help shrink metastatic esophageal or gastric cancer and how the cancer responds to this combination. Bevacizumab is a new drug that is believed to stop the formation of new blood vessels that carry nutrients to tumors. Bevacizumab is approved for use in metastatic colon and rectal cancer. Docetaxel, cisplatin and irinotecan are traditional chemotherapy agents that have been tested together in another clinical trial for esophageal and gastric cancer. It is hoped that adding bevacizumab to this regimen will make the treatment more effective.

Condition Intervention Phase
Esophageal Cancer Stomach Cancer Drug: Bevacizumab Drug: Docetaxel Drug: Cisplatin Drug: Irinotecan Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Peter C. Enzinger, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 10-month Progression-Free Survival Rate [ Time Frame: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 10 months. ]
    10-month progression-free survival rate is the probability of patients remaining alive and progression-free at 10-months from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.


Secondary Outcome Measures:
  • Best Response [ Time Frame: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles). ]
    Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria.

  • Overall Survival [ Time Frame: Patients in the study cohort were followed for a median of 12.2 month (up to 40 months). ]
    Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods.

  • Progression-Free Survival [ Time Frame: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles). ]
    Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Patients alive and progression-free at last follow-up are censored. Per RECIST 1.0 criteria: progressive disease is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.


Enrollment: 38
Study Start Date: September 2006
Study Completion Date: October 2016
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA)
Patients received bevacizumab 10 mg/kg IV on day 1 every 3 weeks while on study. Additionally, they received docetaxel 30 mg/m2 IV over 30 minutes, followed by cisplatin 25 mg/m2 IV over 30 minutes, followed by irinotecan 50 mg/m2 IV over 30 minutes on days 1 and 8 of each 3-week cycle until disease progression or unacceptable toxicity. Dose reductions were not permitted for bevacizumab although treatment could be held up to 2 months. If bevacizumab was discontinued, treatment with other agents could continue. When docetaxel, cisplatin, or irinotecan was held on day 1 of a cycle, all agents were held.
Drug: Bevacizumab
Other Name: Avastin
Drug: Docetaxel
Other Name: Taxotere, Docefrez
Drug: Cisplatin
Other Name: Platinol-AQ, Platinol
Drug: Irinotecan
Other Name: Camptosar

Detailed Description:

OBJECTIVES:

Primary

To determine the 10-month progression-free survival rate for the combination of TPC and Bevacizumab in patients with metastatic esophageal or gastric cancer

Secondary

  • To determine the response rate (RECIST) and median duration of response
  • To determine overall survival
  • To determine toxicity

Exploratory

  • To explore if 7/7 and 7/6 UGT1A1 polymorphisms correlate with grade III/IV irinotecan-related diarrhea and neutropenia when irinotecan is given at relatively low dose to patients with esophageal and gastric cancer
  • To correlate expression of tumoral and serum VEGF with response and survival
  • To correlate TGF alpha levels and tumor microvessel density with clinical activity
  • To examine circulating endothelial cells (CECs) as surrogate markers of antitumor activity of bevacizumab

DESIGN This trial will use a single stage design to differentiate a >/= 50% rate of 10-month progression-free survival from a </= 30% rate. The proposed regimen would be promising if at least 15 of 35 patients were alive and progression-free at 10 months.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed, unresectable esophageal or gastric carcinoma (carcinoma=adenocarcinoma or squamous cell carcinoma)
  • Measurable disease greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT) scan or 2 cm or greater by other radiographic technique
  • Lesions must be measurable in at least one dimension
  • Bone lesions, ascites, and effusions are not measurable
  • 18 years of age or older
  • ECOG performance status 0 or 1
  • Life expectancy of at least 12 weeks
  • Adequate bone marrow function
  • Adequate renal function
  • Adequate liver function

Exclusion Criteria:

  • Prior chemotherapy (except as part of pre- or post-operative therapy, completed more than 1 year prior to start day of this protocol)
  • History of severe hypersensitivity to bevacizumab, docetaxel, cisplatin, irinotecan, or drugs formulated with polysorbate 80
  • Current, recent (within 4 weeks) or planned participation in an experimental drug study
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures, such as fine needle aspirations, port-a-cath placement, or core biopsies within 7 days prior to Day 0 of study
  • Myocardial infarction or stroke in past 6 months
  • Blood pressure of > 150/100 mmHg
  • Unstable angina
  • New York Heart Association (NYHA) grade II or greater congestive heart failure
  • Clinically significant peripheral vascular disease
  • Persistent bleeding from primary tumor, while off anticoagulants, requiring repeated transfusions
  • Evidence of bleeding diathesis or coagulopathy
  • Uncontrolled serious medical or psychiatric illness
  • Uncontrolled diarrhea
  • Peripheral neuropathy > grade 1
  • Clinically apparent central nervous system metastases or carcinomatous meningitis
  • Other active malignancy other than non-melanoma skin cancer or in situ cervical carcinoma.
  • Urine protein: creatinine ratio of 1.0 or greater at screening
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
  • Serious non-healing wound, ulcer, or bone fracture
  • Pregnant or breast-feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00394433

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Genentech, Inc.
Investigators
Principal Investigator: Peter Enzinger, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Peter C. Enzinger, MD, Overall PI, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00394433     History of Changes
Other Study ID Numbers: 06-100
Study First Received: October 31, 2006
Results First Received: September 26, 2016
Last Updated: July 5, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Peter C. Enzinger, MD, Dana-Farber Cancer Institute:
TPCA
Taxotere
Platinum
Avastin
Camptosar
gastric cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Docetaxel
Irinotecan
Cisplatin
Bevacizumab
Camptothecin
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 18, 2017