Esophageal CancerPhase 2NCT00394433
Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
A Phase 2 study testing Bevacizumab, Docetaxel and Cisplatin in people with Esophageal Cancer and Stomach Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Cancer, Stomach Cancer
- What is being tested?
- Bevacizumab, Docetaxel and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2006to Oct 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- Life expectancy of at least 12 weeks
- Adequate bone marrow function
- Adequate renal function
- Adequate liver function
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
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.
Read the 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.
- Conditions
- Esophageal Cancer, Stomach Cancer
- Being tested
- Bevacizumab, Docetaxel, Cisplatin, Irinotecan
- Keywords
- TPCA, Taxotere, Platinum, Avastin, Camptosar, gastric cancer
- Medical subject headings
- Esophageal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
DocetaxelDrug
Also called Taxotere, Docefrez
CisplatinDrug
Also called Platinol-AQ, Platinol
IrinotecanDrug
Also called Camptosar
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) | Experimental | 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. Receives: Drug: Bevacizumab; Drug: Docetaxel; Drug: Cisplatin; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
10-month Progression-Free Survival Rate
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.
Measured: 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 (3)
Best Response
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.
Measured: 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).
Overall Survival
Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods.
Measured: Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
Progression-Free Survival
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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2006 (estimated)
- Study startSep 2006
- Primary completionNov 2008
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter C. Enzinger, MD, Dana-Farber Cancer Institute
- Investigators
- Peter Enzinger, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00394433
- Sponsor's protocol ID
- 06-100
- Status last verified
- Jul 2017
- First submitted
- 31 Oct 2006
- Last updated
- 1 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
- ClinicalTrials.gov ID
- NCT00394433
- Acronym / sponsor ID
- 06-100
- Conditions
- Esophageal Cancer, Stomach Cancer
- Keywords
- TPCA, Taxotere, Platinum, Avastin, Camptosar, gastric cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Genentech, Inc.
- Study start
- Sep 2006
- Primary completion
- Nov 2008 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 1 Nov 2006 (estimated)
- Results
- Posted 16 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) | Experimental | Drug: Bevacizumab, Drug: Docetaxel, Drug: Cisplatin, Drug: IrinotecanPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Avastin | Drug | Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) |
| DocetaxelAlso: Taxotere, Docefrez | Drug | Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) |
| CisplatinAlso: Platinol-AQ, Platinol | Drug | Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) |
| IrinotecanAlso: Camptosar | Drug | Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) |
Primary outcome
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.
3 secondary outcomes
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).
Overall Survival
Time frame: Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Enzinger, MD principal investigator
Dana-Farber Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Docetaxel and Cisplatin in people with Esophageal Cancer and Stomach Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2017.