Esophageal CancerPhase 2NCT00911820
Cisplatin, Irinotecan and Bevacizumab (PCA) Versus Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
A Phase 2 study testing Bevacizumab, Cisplatin and Irinotecan in people with Esophageal Cancer and Gastric Cancer, run by Dana-Farber Cancer Institute at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Cancer, Gastric Cancer, Stomach Cancer
- What is being tested?
- Bevacizumab, Cisplatin and Irinotecan
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2009to Aug 2013
- 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, GE junction or gastric adenocarcinoma (including adenosquamous, or undifferentiated carcinoma). Measurable disease is not required.
- 18 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
Who cannot join
- 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
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- 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
- Peripheral neuropathy
- No known brain or other CNS metastasis by history or clinical examination
- Other active malignancy other than non-melanoma skin cancer or in-situ cervical carcinoma. A resected or previously treated cancer (other than in-situ carcinoma) must have demonstrated no evidence of recurrence for at least 3 years
- Urine protein:creatinine ratio 1.0 or greater at screening
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess with 6 months of C1 D1
- Serious, non-healing wound, ulcer or bone fracture
- Pregnant or breast feeding
- Inability to comply with study and/or follow-up procedures
- History of HIV seropositivity, hepatitis C virus, acute or chronic hepatitis B, or other serious chronic infection
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02214
Texas Oncology Research
Dallas, Texas, 75251
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
About this study
Official title: A Randomized, Multicenter, Phase II Trial of Cisplatin, Irinotecan and Bevacizumab (PCA) vs. Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
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.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate progression-free survival at 7 months in metastatic esophageal and gastric patients treated with either PCA or TPCA
Secondary
- To determine overall survival
- To determine the response rate (RECIST) in measurable disease patients
- To evaluate type and severity of toxicities associated with each regimen
Exploratory:
- To correlate expression of tumoral and serum VEGF with response and survival
- To correlate TGF alpha levels and tumor microvessel density with clinical activity of the combination of PCA or TPCA
- To examine circulating endothelial cells (CECs) as surrogate markers of antitumor activity of bevacizumab
- 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
DESIGN:
This trial was designed to compare 7-month progression-free survival between arms. The hypothesis was that TPCA would have superior outcome over PCA (70% vs 50%). With 40 eligible patients per arm followed for 1 year there was 80% power to detect a hazard ratio of 0.48 using the log-rank test at a one-sided type I error rate of 5%. Stratification factors were ECOG performance status 0/1 vs 2 and site of primary tumor (gastric vs GE junction/esophageal).
- Conditions
- Esophageal Cancer, Gastric Cancer, Stomach Cancer
- Being tested
- Bevacizumab, Cisplatin, Irinotecan, Docetaxel
- 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
CisplatinDrug
Also called Platinol-AQ, Platinol
IrinotecanDrug
Also called Camptosar
DocetaxelDevice
Also called Taxotere, Docefrez
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cisplatin; Drug: Irinotecan; Device: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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 up to approximately 2.5 years as of this analysis.
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 duration was a median of 5 cycles (up to approximately 1 year) in this study cohort as of this analysis..
Overall Response (OR) Rate
Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Measured: 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
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; Patients were followed for up to 2.5 years as of this analysis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2009 (estimated)
- Study startJul 2009
- Primary completionApr 2012
- Study completionAug 2013
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital, SCRI Development Innovations, LLC, Texas Oncology Cancer Center, Genentech, Inc.
- Responsible party
- Principal investigator, Peter C. Enzinger, MD, Dana-Farber Cancer Institute
- Investigators
- Peter C. Enzinger, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00911820
- Sponsor's protocol ID
- 09-039
- Status last verified
- Oct 2022
- First submitted
- 29 May 2009
- Last updated
- 8 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter, Phase II Trial of Cisplatin, Irinotecan and Bevacizumab (PCA) vs. Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
- ClinicalTrials.gov ID
- NCT00911820
- Acronym / sponsor ID
- 09-039
- Conditions
- Esophageal Cancer, Gastric Cancer, Stomach Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital, SCRI Development Innovations, LLC, Texas Oncology Cancer Center, Genentech, Inc.
- Study start
- Jul 2009 (actual)
- Primary completion
- Apr 2012 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 2 Jun 2009 (estimated)
- Results
- Posted 9 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To evaluate progression-free survival at 7 months in metastatic esophageal and gastric patients treated with either PCA or TPCA
Secondary
- To determine overall survival
- To determine the response rate (RECIST) in measurable disease patients
- To evaluate type and severity of toxicities associated with each regimen
Exploratory:
- To correlate expression of tumoral and serum VEGF with response and survival
- To correlate TGF alpha levels and tumor microvessel density with clinical activity of the combination of PCA or TPCA
- To examine circulating endothelial cells (CECs) as surrogate markers of antitumor activity of bevacizumab
- 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
DESIGN:
This trial was designed to compare 7-month progression-free survival between arms. The hypothesis was that TPCA would have superior outcome over PCA (70% vs 50%). With 40 eligible patients per arm followed for 1 year there was 80% power to detect a hazard ratio of 0.48 using the log-rank test at a one-sided type I error rate of 5%. Stratification factors were ECOG performance status 0/1 vs 2 and site of primary tumor (gastric vs GE junction/esophageal).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: PCA | Active comparator | Drug: Bevacizumab, Drug: Cisplatin, Drug: IrinotecanPatients 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. |
| Arm B: TPCA | Active comparator | Drug: Cisplatin, Drug: Irinotecan, Device: DocetaxelPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed, unresectable esophageal, GE junction or gastric adenocarcinoma (including adenosquamous, or undifferentiated carcinoma). Measurable disease is not required.
- 18 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.
Key exclusion criteria (24 listed)
- 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
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 | Arm A: PCA |
| CisplatinAlso: Platinol-AQ, Platinol | Drug | Arm A: PCA, Arm B: TPCA |
| IrinotecanAlso: Camptosar | Drug | Arm A: PCA, Arm B: TPCA |
| DocetaxelAlso: Taxotere, Docefrez | Device | Arm B: TPCA |
Primary outcome
7-month Progression-Free Survival
Time frame: 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.
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.
4 secondary outcomes
Overall Survival
Time frame: Patients in the study cohort were followed up to approximately 2.5 years as of this analysis.
Best Response
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- 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 C. Enzinger, MD principal investigator
Dana-Farber Cancer Institute
4 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, Cisplatin and Irinotecan in people with Esophageal Cancer and Gastric Cancer, run by Dana-Farber Cancer Institute at 4 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 6 inclusion and 24 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 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 9 Nov 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?
7-month Progression-Free Survival (time frame: 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.). 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 8 Nov 2022.