Esophageal CancerPhase 2NCT00737438
Pre-operative Chemotherapy Plus Bevacizumab With Early Salvage Therapy Based on PET Assessment of Response in Patients With Locally Advanced But Resectable Gastric and GEJ Adenocarcinoma
A Phase 2 study testing epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecan in people with Esophageal Cancer and Gastric Cancer, run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.
Trial summary
This study is being done to find out how effective a new treatment strategy is on your cancer. In this strategy, the response your tumor has to the first cycle of therapy will help select the next treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Cancer, Gastric Cancer
- What is being tested?
- epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesUnited States
- Study dates
- Aug 2008to Feb 2015
- 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
- All patients must have microscopically confirmed adenocarcinoma of the stomach or GE junction. Tumors involving the GE junction must have the bulk of their disease in the stomach; tumors of the distal esophagus that extend less than 2cm into the stomach are ineligible for this study.
- All patients must be considered candidates for surgical resection.
- Patients must have FDG-avid malignancies.
- FDG avid tumors are defined as primary tumors with an increased tracer uptake in the region of the tumor that has an SUV > or = to 3.5 or a tumor:liver ratio > or = to 1.5, and felt to be "probably" or "definitely malignant" (i.e. likelihood score of 3 or 4) by the reference nuclear medicine physician.
- All patients must have localized cancer potentially curable by surgery. The tumor stage should be T any N+ M0 or T3-T4a N any M0(AJCC 7th Edition), by staging that includes a CT scan and either laparoscopy or endoscopic ultrasound. Patients with T1-2 N0M0 or patients with distant metastatic disease (i.e. M1) are ineligible. Any sites of suspected M1 disease by these criteria must be proven to be M0 prior to entrance into the neoadjuvant study.
- Patients may not have received prior chemotherapy or radiation for this disease.
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- The patient is at least 18 years of age.
- If female and of child bearing potential, the patient has a negative serum pregnancy test within 14 days of starting therapy, and, if male or female and of child bearing potential, currently uses (and agree to continue to use throughout the study) an acceptable method of birth control (IUD, oral contraceptive, or barrier device). They should agree to continue to use these for three months after the study is completed. The patient also agrees to refrain from nursing during the duration of the study and for at least two months after the study is completed. Pregnant or lactating females are not included because the anti-proliferative effects of bevacizumab may be harmful to the fetus or developing infant.
- Karnofsky performance status > or = to 70%.
- The patient has adequate hematopoietic function, defined as having a total neutrophil count (ANC) ≥ or = to 1500/mm3, a platelet count ≥ or = 100,000/mm3. The patient has adequate renal and hepatic function, defined as having a serum creatinine ≤ or = to 2.5 mg/dl, urinalysis demonstrating < 2+ proteinuria and/or a urine protein/creatinine (UPC) ratio < 1.0. LFTs include a total serum bilirubin ≤ than or = to 2 x ULN, serum AST (SGOT)/ALT (SGPT) and ALK PHOS < than or = to 2.5 ULN.
- The patient has a PT (INR) < than or = to 1.5 and an PTT < than or = to 3 seconds above the upper limits of normal (i.e. at MSKCC PTT < than or = to 37.7 sec) if the patient is not on anticoagulation.
- If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment
- If using warfarin, the subject must have an in-range INR (usually between 2 and 3) and on a stable dose of warfarin.
- The subject must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices).
- Ability to understand informed consent and signing of written informed consent document prior to the initiation of treatment.
Who cannot join
- Any metastatic disease.
- Significant cardiac disease as defined as:
- New York Heart Association (NYHA) grade II or greater (see Appendix B for NYHA Class),
- congestive heart failure, or history of myocardial infarction or unstable angina within 12 months of study enrollment
- Any history of stroke or transient ischemic attack at any time.
- Pregnant (positive pregnancy test) or lactating women. A pregnancy test will be performed on sexually active women of childbearing potential prior to entry into the study. Treatment may not begin until the results of the pregnancy test are ascertained.
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- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) on antihypertensive therapy.
- Any prior history of hypertensive crisis or hypertensive encephalopathy.
- Significant vascular disease (e.g. aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease (ie. grade 2 or higher).
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting therapy (eg. day 0).
- Core biopsy or other minor surgical procedure, excluding placement of a vascular device, within 7 days of starting therapy.
- Evidence of bleeding diathesis or coagulopathy.
- Proteinuria at screening as demonstrated by either
- Urine protein:creatinine (UPC) ratio > 1.0 at screening, or
- Urine dipstick for proteinuria > or = to 2+ (patients discovered to have > or = to 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < than or = to 1g of protein in 24 hours to be eligible).
- Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
- Serious, non-healing wound, ulcer, or bone fracture.
- Grade 2 or greater pre-existing peripheral neuropathy.
- Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol.
- Any concurrent active malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer or carcinoma-in-situ of the uterine cervix. Patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial.
- Clinically significant hearing loss.
- EKG evidence of acute ischemia or significant conduction abnormality, as determined by the treating physician.
- Known hypersensitivity to Chinese hamster ovary cell products, other recominant human antibodies, or to any component of bevacizumab.
- Patients with any other medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in a clinical trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Memorial Sloan Kettering Cancer Center
Basking Ridge, New Jersey
Memorial Sloan Kettering Cancer Center
Commack, New York
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Cancer Center
Rockville Centre, New York
Memoral Sloan Kettering Cancer Center@Phelps
Sleepy Hollow, New York
About this study
Official title: A Phase II Study of Pre-operative Chemotherapy Plus Bevacizumab With Early Salvage Therapy Based on PET Assessment of Response in Patients With Locally Advanced But Resectable Gastric and GEJ Adenocarcinoma
This study is being done to find out how effective a new treatment strategy is on your cancer. In this strategy, the response your tumor has to the first cycle of therapy will help select the next treatments. We also will find out the effects, both good and/or bad, a drug called bevacizumab has on you and your tumor when given with chemotherapy.
- Conditions
- Esophageal Cancer, Gastric Cancer
- Being tested
- epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecan
- Keywords
- BEVACIZUMAB (AVASTIN), CAPECITABINE (ORAL), CISPLATIN, EPIRUBICIN, IRINOTECAN (CPT-11) CAMPTOSAR, TAXOTERE (DOCETAXEL), ESOPHAGUS, STOMACH, 08-081
- 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.
epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecanDrug
Also called Patients who have a poor PET response to cycle 1 of ECX plus bevacizumab, (eg. < 35% FDG reduction on the week 3 PET scan compared with baseline), will be switched to salvage therapy of docetaxel and irinotecan (DI)., This treatment will be administered on week 1 and 2 of a 3
Patients with FDG avid locally advanced but resectable gastric or GEJ adenocarcinoma will receive preoperative therapy with epirubicin, cisplatin, capecitabine (ECX), and bevacizumab. Each cycle of therapy is 21 days. Near the completion of cycle 1 of therapy (eg during week 3, target days 18-21), patients will undergo a second FDG-PET/CT scan. Note, patients will hold capecitabine for 48 hours prior to the FDG-PET/CT scan.
Patients with a good metabolic response (eg. > 35% reduction in FDG uptake at the primary tumor on the week 3 PET scan as compared with baseline FDG uptake) will continue ECX for 2 additional cycles (cycle 2 and 3).
Cycle 2 will be administered with bevacizumab and cycle 3 will be administered without bevacizumab. Patients will then proceed to surgery approximately 4-6 weeks following the completion of cycle 3. There is a 10-12 week time interval (eg. 70-84 days) between the last bevacizumab treatment and surgery.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Initial chemo for ALL pts (ECX + BEV): Epirubicin 50 mg/m2 d1 every 21 days Cisplatin 60 mg/m2 d1 every 21 days, Capecitabine 625 mg/m2 po bid days 2-21 (held for 48 hours prior to FDG-PET/CT in week 3) Bev 15 mg/kg d1 every 21 days (cycle 1 \& cycle 2 only) Salvage chemotherapy for metabolic non-responders (DI + BEV): Docetaxel 30 mg/m2 d1, d8 every 21 days, CPT-11 50 mg/m2 d1, d8 every 21 days, Bev 15 mg/kg d1, cycle 2 only 2 cycles are planned prior to resection.
Pts who aren't Cisplatin candidates (i.e. Creatinine clearance 40-60/cc, older age, marginal PS,etc.) may get oxaliplatin instead of cisplatin after discus with the PI. Oxaliplatin will be admin at 130 mg/m2 on day 1 every 21 days. Pts who aren't able to get Capecitabine (i.e. insurance restriction, unable to swallow, etc.) may get infusional fluorouracil instead of capecitabine after discus with the PI. Fluorouracil will be admin at 200 mg/m2/d x 21 days (held for 48 hours prior to FDGPET/ CT scan in week 3 of cycle 1). Receives: Drug: epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Will be Characterized by the Patient's FDG-PET Scan
A good early FDG Response is a reduction in FDG uptake on the week 3 PET scan of > or = to 35% from baseline. An FDG PET non-responder will be defined as having a decrease of < 35% on the week 3 PET scan compared with baseline.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionFeb 2015
- Study completionFeb 2015
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 Memorial Sloan Kettering Cancer CenterThe 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
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Weill Medical College of Cornell University
- Responsible party
- Sponsor
- Investigators
- David Ilson, MD,PhD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00737438
- Sponsor's protocol ID
- 08-081
- Status last verified
- Jan 2016
- First submitted
- 15 Aug 2008
- Last updated
- 3 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pre-operative Chemotherapy Plus Bevacizumab With Early Salvage Therapy Based on PET Assessment of Response in Patients With Locally Advanced But Resectable Gastric and GEJ Adenocarcinoma
- ClinicalTrials.gov ID
- NCT00737438
- Acronym / sponsor ID
- 08-081
- Conditions
- Esophageal Cancer, Gastric Cancer
- Keywords
- BEVACIZUMAB (AVASTIN), CAPECITABINE (ORAL), CISPLATIN, EPIRUBICIN, IRINOTECAN (CPT-11) CAMPTOSAR, TAXOTERE (DOCETAXEL), ESOPHAGUS, STOMACH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc., Weill Medical College of Cornell University
- Study start
- Aug 2008
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 19 Aug 2008 (estimated)
- Results
- Posted 3 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to find out how effective a new treatment strategy is on your cancer. In this strategy, the response your tumor has to the first cycle of therapy will help select the next treatments. We also will find out the effects, both good and/or bad, a drug called bevacizumab has on you and your tumor when given with chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecanInitial chemo for ALL pts (ECX + BEV): Epirubicin 50 mg/m2 d1 every 21 days Cisplatin 60 mg/m2 d1 every 21 days, Capecitabine 625 mg/m2 po bid days 2-21 (held for 48 hours prior to FDG-PET/CT in week 3) Bev 15 mg/kg d1 every 21 days (cycle 1 \& cycle 2 only) Salvage chemotherapy for metabolic non-responders (DI + BEV): Docetaxel 30 mg/m2 d1, d8 every 21 days, CPT-11 50 mg/m2 d1, d8 every 21 days, Bev 15 mg/kg d1, cycle 2 only 2 cycles are planned prior to resection. Pts who aren't Cisplatin candidates (i.e. Creatinine clearance 40-60/cc, older age, marginal PS,etc.) may get oxaliplatin instead of cisplatin after discus with the PI. Oxaliplatin will be admin at 130 mg/m2 on day 1 every 21 days. Pts who aren't able to get Capecitabine (i.e. insurance restriction, unable to swallow, etc.) may get infusional fluorouracil instead of capecitabine after discus with the PI. Fluorouracil will be admin at 200 mg/m2/d x 21 days (held for 48 hours prior to FDGPET/ CT scan in week 3 of cycle 1). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- All patients must have microscopically confirmed adenocarcinoma of the stomach or GE junction. Tumors involving the GE junction must have the bulk of their disease in the stomach; tumors of the distal esophagus that extend less than 2cm into the stomach are ineligible for this study.
- All patients must be considered candidates for surgical resection.
- Patients must have FDG-avid malignancies.
- FDG avid tumors are defined as primary tumors with an increased tracer uptake in the region of the tumor that has an SUV > or = to 3.5 or a tumor:liver ratio > or = to 1.5, and felt to be "probably" or "definitely malignant" (i.e. likelihood score of 3 or 4) by the reference nuclear medicine physician.
- All patients must have localized cancer potentially curable by surgery. The tumor stage should be T any N+ M0 or T3-T4a N any M0(AJCC 7th Edition), by staging that includes a CT scan and either laparoscopy or endoscopic ultrasound. Patients with T1-2 N0M0 or patients with distant metastatic disease (i.e. M1) are ineligible. Any sites of suspected M1 disease by these criteria must be proven to be M0 prior to entrance into the neoadjuvant study.
Key exclusion criteria (26 listed)
- Any metastatic disease.
- Significant cardiac disease as defined as:
- New York Heart Association (NYHA) grade II or greater (see Appendix B for NYHA Class),
- congestive heart failure, or history of myocardial infarction or unstable angina within 12 months of study enrollment
- Any history of stroke or transient ischemic attack at any time.
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 |
|---|---|---|
| epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecanAlso: Patients who have a poor PET response to cycle 1 of ECX plus bevacizumab, (eg. < 35% FDG reduction on the week 3 PET scan compared with baseline), will be switched to salvage therapy of docetaxel and irinotecan (DI)., This treatment will be administered on week 1 and 2 of a 3Patients with FDG avid locally advanced but resectable gastric or GEJ adenocarcinoma will receive preoperative therapy with epirubicin, cisplatin, capecitabine (ECX), and bevacizumab. Each cycle of therapy is 21 days. Near the completion of cycle 1 of therapy (eg during week 3, target days 18-21), patients will undergo a second FDG-PET/CT scan. Note, patients will hold capecitabine for 48 hours prior to the FDG-PET/CT scan. Patients with a good metabolic response (eg. > 35% reduction in FDG uptake at the primary tumor on the week 3 PET scan as compared with baseline FDG uptake) will continue ECX for 2 additional cycles (cycle 2 and 3). Cycle 2 will be administered with bevacizumab and cycle 3 will be administered without bevacizumab. Patients will then proceed to surgery approximately 4-6 weeks following the completion of cycle 3. There is a 10-12 week time interval (eg. 70-84 days) between the last bevacizumab treatment and surgery. | Drug | 1 |
Primary outcome
Overall Response Will be Characterized by the Patient's FDG-PET Scan
Time frame: 2 years
A good early FDG Response is a reduction in FDG uptake on the week 3 PET scan of > or = to 35% from baseline. An FDG PET non-responder will be defined as having a decrease of < 35% on the week 3 PET scan compared with baseline.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
David Ilson, MD,PhD principal investigator
Memorial Sloan Kettering Cancer Center
5 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 epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecan in people with Esophageal Cancer and Gastric Cancer, run by Memorial Sloan Kettering Cancer Center at 5 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 15 inclusion and 26 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 3 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 3 Feb 2016). 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?
Overall Response Will be Characterized by the Patient's FDG-PET Scan (time frame: 2 years). 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 3 Feb 2016.