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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

Phase 2
18 Years
Open (Enrolling)
Esophageal Cancer, Gastric Cancer

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Trial Information

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

Inclusion Criteria:

- 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.

- 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

1. If using warfarin, the subject must have an in-range INR (usually between 2 and
3) and on a stable dose of warfarin.

2. 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.

Exclusion Criteria:

- Any metastatic disease.

- Significant cardiac disease as defined as:

- New York Heart Association (NYHA) grade II or greater (see Appendix B for NYHA

- 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

- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To examine the effectiveness of FDG PET directed early switching to salvage chemotherapy + bevacizumab as measured by 2 year disease free survival in the non-PET responding (salvage) population.

Outcome Time Frame:

conclusion of study

Safety Issue:


Principal Investigator

David Ilson, MD,PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

August 2008

Completion Date:

August 2013

Related Keywords:

  • Esophageal Cancer
  • Gastric Cancer
  • 08-081
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Stomach Neoplasms



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Memorial Sloan-Kettering Cancer CenterBasking Ridge, New Jersey  
Memoral Sloan Kettering Cancer Center@PhelpsSleepy Hollow, New York