Clinical trial NCT00394433: Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
Official title: A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Stomach Cancer
Keywords: TPCA
Taxotere
Platinum
Avastin
Camptosar
gastric cancer
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: Genentech, Inc.
First posted: 2006-11-01
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 10-month Progression-Free Survival Rate
timeFrame: 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.
Secondary outcomes:
measure: Best Response
timeFrame: 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).
measure: Overall Survival
timeFrame: Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
measure: Progression-Free Survival
timeFrame: 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).
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Peter Enzinger, MD
role: PRINCIPAL_INVESTIGATOR
References: