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

NCT00911820 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 09-039
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 4

Brief Summary

There is no clear standard of care for metastatic stomach or esophageal cancer in the United States. The purpose of this research study is to determine the differences between two regimens of chemotherapy; Arm A: PCA (Cisplatin, Irinotecan and Bevacizumab) and Arm B: TPCA (Docetaxel, Cisplatin, Irinotecan and Bevacizumab). Docetaxel, Cisplatin, and Irinotecan are traditional chemotherapy drugs. Bevacizumab is an antibody (a protein that attacks a foreign substance in the body). Bevacizumab is believed to stop the formation of new blood vessels that carry nutrients to tumors. Both of the chemotherapy regimens (PCA and TPCA) have been studied in patients with esophageal and gastric cancer, and we are trying to determine if one regimen will keep your cancer from growing and improve how long you can live.

Conditions

Esophageal Cancer; Gastric Cancer; Stomach Cancer

Outcome Measures

Primary Outcomes (1)

• 7-month Progression-Free Survival

  7-month progression-free survival is the probability of patients remaining alive and progression-free at 7-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.

  Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Relevant for this endpoint was disease status at 7 months of follow-up.

Secondary Outcomes (4)

• Overall Survival

  Patients in the study cohort were followed up to approximately 2.5 years as of this analysis.

• Best Response

  Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment duration was a median of 5 cycles (up to approximately 1 year) in this study cohort as of this analysis..

• Overall Response (OR) Rate

  Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment duration was a median of 5 cycles (up to approximately 1 year) in this study cohort as of this analysis.

• Progression-Free Survival

  Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Patients were followed for up to 2.5 years as of this analysis.

Study Arms (2)

Arm A: PCA

ACTIVE COMPARATOR

Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally, on days 1 and 8 of each cycle, patients received cisplatin 30 mg/m2 IV over 30 minutes and then irinotecan 65 mg/m2 IV over 30 minutes of each 3-week cycle. Treatment could continue until disease progression or unacceptable toxicity.

Drug: Bevacizumab; Drug: Cisplatin; Drug: Irinotecan

Arm B: TPCA

ACTIVE COMPARATOR

Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally on days 1 and 8 of each cycle, patients received docetaxel 30 mg/m2 IV over 30 minutes followed by cisplatin 25 mg/m2 IV over 30 minutes and then irinotecan 50 mg/m2 IV over 30 minutes of each 3-week cycle.

Drug: Cisplatin; Drug: Irinotecan; Device: Docetaxel

Interventions

Bevacizumab DRUG

Also known as: Avastin

Arm A: PCA

Cisplatin DRUG

Also known as: Platinol-AQ, Platinol

Arm A: PCA; Arm B: TPCA

Irinotecan DRUG

Also known as: Camptosar

Arm A: PCA; Arm B: TPCA

Docetaxel DEVICE

Also known as: Taxotere, Docefrez

Arm B: TPCA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, unresectable esophageal, GE junction or gastric adenocarcinoma (including adenosquamous, or undifferentiated carcinoma). Measurable disease is not required.
• years of age or older
• ECOG Performance Status=2
• Life expectancy of 12 weeks or greater
• Adequate bone marrow, renal and liver function as outlined in the protocol.
• Men and women of childbearing potential must use adequate contraception

You may not qualify if:

• Prior chemotherapy (except as part of pre- or post-operative therapy, completed at least 1 prior to start of this protocol).
• Squamous cell carcinoma histology of esophageal, GE junction or gastric tumor
• Known history of allergy or hypersensitivity to Chinese hamster ovary products, polysorbate 80, or any of the study drugs
• Treatment or planned participation in an experimental drug study within 4 weeks of C1 D1. Concurrent use of herbal medications or other alternative therapies
• Major surgical procedures, such as fine needle aspirations, port-a-cath placement, or core biopsies, within 7 days of cycle 1 day 1
• Palliative radiation to 25% or less of bone marrow, must be completed \> 2 weeks prior to day 1, palliative radiation to \> 25% of bone marrow, must be completed \> 4 weeks prior to day 1
• Myocardial infarction, unstable angina, CVA or TIA or other thrombotic event in the past six months
• Inadequately controlled hypertension (defined as systolic blood pressure of \>150mmHg and/or diastolic blood pressure of \> 100mmHg). Initiation of antihypertensive medication is recommended, however adequate control of blood pressure must be documented prior to C1 D1
• No history of prior hypertensive crisis or hypertensive encephalopathy
• NYHA Grade II or greater congestive heart failure
• Clinically significant peripheral vascular disease
• Active bleeding from primary tumor
• Evidence of bleeding diatheses or coagulopathy (other than deep venous thrombosis, portal vein thrombosis, pulmonary embolism, or atrial fibrillation). Patients on therapeutic anticoagulation may be enrolled provided they have been clinically stable on anticoagulation for a least 2 weeks prior to C1 D1.
• Uncontrolled serious medical or psychiatric illness
• Uncontrolled diarrhea

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Massachusetts General Hospital: collaborator
• SCRI Development Innovations, LLC: collaborator
• Texas Oncology Cancer Center: collaborator
• Genentech, Inc.: collaborator

Study Sites (4)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology Research

Dallas, Texas, 75251, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms

Interventions

Bevacizumab; Cisplatin; Irinotecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Peter Enzinger, MD
• Organization: Dana-Farber Cancer Insitute

Peter_Enzinger@dfci.harvard.edu

617-632-6855

Study Officials

• Peter C. Enzinger, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 29, 2009
• First Posted: June 2, 2009
• Study Start: July 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: August 1, 2013
• Last Updated: November 8, 2022
• Results First Posted: November 9, 2017

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)