Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Not Recruiting

Trial ID: NCT00951496


This randomized phase III trial studies bevacizumab and intravenous (given into a vein) chemotherapy to see how well they work compared with bevacizumab and intraperitoneal (given into the abdominal cavity) chemotherapy in treating patients with stage II-III ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block the ability of tumor cells to grow and spread by blocking the growth of new blood vessels necessary for tumor growth. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving bevacizumab together with intravenous chemotherapy is more effective than giving bevacizumab together with intraperitoneal chemotherapy in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

Official Title

A Phase III Clinical Trial of Bevacizumab With IV Versus IP Chemotherapy in Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma

Stanford Investigator(s)

Jonathan S. Berek, MD, MMSc
Jonathan S. Berek, MD, MMSc

Laurie Kraus Lacob Professor


Inclusion Criteria:

   - Patients with a histologic diagnosis of epithelial ovarian, fallopian tube, or primary
   peritoneal carcinoma, stage II, III, or IV with either optimal (=< 1 cm residual
   disease) or suboptimal residual disease; in the event of a higher priority Phase III
   Gynecologic Oncology Group (GOG) protocol becoming available for suboptimal and/or
   stage IV patients, the eligibility of this study will narrow and exclude those
   patients at those participating institutions (11/02/2009)

      - Note: patients with suboptimal disease/and or stage IV will not be eligible as of
      April 1, 2011; they should be enrolled on GOG-0262 (03/14/11)

      - All patients must have a procedure for determining diagnosis of epithelial
      ovarian, fallopian tube, primary peritoneal, with appropriate tissue for
      histologic evaluation; the minimum surgery required is an abdominal surgery
      providing tissue for histologic evaluation and establishing and documenting the
      primary site and stage, as well as a maximal effort at tumor debulking; if
      additional surgery was performed, it should have been in accordance with
      appropriate surgery for ovarian or peritoneal carcinoma described in the GOG
      Surgical Procedures Manual (

   - Patients with the following histologic epithelial cell types are eligible: serous
   adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated
   carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell
   carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified
   (N.O.S.); however, the histologic features of the tumor must be compatible with a
   primary Müllerian epithelial adenocarcinoma; if doubt exists, it is recommended that
   the investigator should have the slides reviewed by an independent pathologist prior
   to entry; patients may have co-existing endometrial cancer so long as the primary
   origin of invasive tumor is ovarian or peritoneal; Note: patients with mucinous, low
   grade and clear cell disease are eligible unless there is a higher priority GOG trial
   open (11/02/2009) (08/16/2010)

   - Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to
   Common Terminology Criteria for Adverse Events v3.0 (CTCAE) grade 1; this ANC cannot
   have been induced or supported by granulocyte colony stimulating factors

   - Platelets greater than or equal to 100,000/mcl

   - Creatinine no greater than institutional upper limits of normal (03/29/10)

   - Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (CTCAE grade 1)

   - Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than or equal to
   2.5 x ULN (CTCAE grade 1)

   - Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE grade 1)

   - Neuropathy (sensory and motor) less than or equal to CTCAE grade 1

   - Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN
   (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
   therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 times the upper
   limit of normal (heparin, Lovenox or alternative anticoagulants are acceptable); this
   corresponds to CTCAE version 3.0 grade 1 one or less (11/02/2009) (03/29/10)

   - Patients with a GOG performance status of 0, 1, or 2

   - Patients must be entered and treated within 12 weeks of their most recent surgery
   performed for the combined purpose of diagnosis, staging and/or cytoreduction; the
   first cycle of chemotherapy should not be given until at least seven days after the
   most recent major surgery, which allows 4 weeks to have elapsed prior to the first
   bevacizumab dose; (placement of venous or peritoneal access devices will be considered
   minor surgery) (03/29/10)

   - Patients who have met the pre-entry requirements specified

   - An approved informed consent and authorization permitting release of personal health
   information must be signed by the patient or guardian

   - Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy
   as indicated at the lowest effective dose(s) for control of menopausal symptoms at any
   time, but high dose progestin as an appetite stimulant should be avoided (03/29/10)

Exclusion Criteria:

   - Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly
   "tumors of low malignant potential") or recurrent invasive epithelial ovarian cancer
   treated with surgery only (such as those with stage IA or IB low grade lesions) are
   not eligible; patients with a prior diagnosis of a borderline tumor that was
   surgically resected and who subsequently develop an unrelated, new invasive epithelial
   ovarian or peritoneal primary cancer are eligible, provided that they have not
   received prior chemotherapy for any ovarian tumor

   - Patients with a history of other invasive malignancies, with the exception of
   non-melanoma skin cancer and other specific malignancies are excluded if there is any
   evidence of the other malignancy being present within the last five years; patients
   are also excluded if their previous cancer treatment contraindicates this protocol
   therapy (11/02/2009)

   - Patients who have received prior radiotherapy to any portion of the abdominal cavity
   or pelvis are excluded; prior radiation for localized cancer of the breast, head and
   neck, or skin is permitted, provided that it was completed more than three years prior
   to registration, and the patient remains free of recurrent or metastatic disease

   - Patients who have received prior chemotherapy for any abdominal or pelvic tumor
   including neo-adjuvant chemotherapy for their ovarian or primary peritoneal cancer are
   excluded; patients may have received prior adjuvant chemotherapy for localized breast
   cancer, provided that it was completed more than three years prior to registration,
   and that the patient remains free of recurrent or metastatic disease

   - Patients who have received any targeted therapy (including but not limited to
   vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management
   of their epithelial ovarian or peritoneal primary cancer

   - Patients with synchronous primary endometrial cancer, or a past history of primary
   endometrial cancer, are excluded, unless all of the following conditions are met:
   stage not greater than IB; no more than superficial myometrial invasion, without
   vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary
   serous, clear cell or other FIGO grade 3 lesions

   - Patients with acute hepatitis or active infection that requires parenteral antibiotics

   - Patients with serious non-healing wound, ulcer, or bone fracture; this includes
   history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
   within 28 days; patients with granulating incisions healing by secondary intention
   with no evidence of fascial dehiscence or infection are eligible but require weekly
   wound examinations

   - Patients with active bleeding or pathologic conditions that carry high risk of
   bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major

   - Patients with history or evidence upon physical examination of major central nervous
   system (CNS) disease (for example: primary brain tumor, metastatic cancer in the
   brain, seizures not controlled with standard medical therapy, any brain metastases, or
   history of cerebrovascular accident [CVA, stroke], transient ischemic attack [TIA] or
   subarachnoid hemorrhage within six months of the first date of treatment on this
   study) (11/02/2009) (03/29/10)

   - Patients with clinically significant cardiovascular disease; this includes:

      - Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mmHg

      - Myocardial infarction or unstable angina < 6 months prior to registration

      - New York Heart Association (NYHA) grade II or greater congestive heart failure

      - Serious cardiac arrhythmia requiring medication; this does not include
      asymptomatic atrial fibrillation with controlled ventricular rate, or past
      history of supraventricular tachycardia controlled with medications and that is
      asymptomatic (03/29/10)

      - CTCAE grade 2 or greater peripheral vascular disease (at least brief (< 24 hrs)
      episodes of ischemia managed non-surgically and without permanent deficit)

   - Patients with known hypersensitivity to Chinese hamster ovary cell products or other
   recombinant human or humanized antibodies; patients with known allergy to Cremophor or
   polysorbate 80

   - Patients with clinically significant proteinuria; urine protein should be screened by
   urine protein-creatinine ratio (UPCR); patients must have a UPCR < 1.0 to allow
   participation in the study

   - Patients with or with anticipation of invasive procedures as defined below:

      - Major surgical procedure, open biopsy or significant traumatic injury within 28
      days prior to the first date of bevacizumab therapy (cycle 2)

      - Major surgical procedure anticipated during the course of the study; this
      includes, but is not limited to abdominal surgery (laparotomy or laparoscopy)
      prior to disease progression, such as colostomy or enterostomy reversal, interval
      or secondary cytoreductive surgery, or second look surgery

      - Core biopsy, within 7 days prior to the first date of bevacizumab therapy (cycle

   - Patients with GOG performance grade of 3 or 4

   - Patients who are pregnant or nursing; patients of childbearing potential must agree to
   use contraceptive measures during study therapy and for at least six months after
   completion of bevacizumab therapy

   - Patients who have received prior therapy with any anti-vascular endothelial growth
   factor (VEGF) drug, including bevacizumab

   - Patients with clinical symptoms or signs of gastrointestinal obstruction and/ or those
   who require parenteral hydration and/or nutrition; patients with history or current
   diagnosis of inflammatory bowel disease are not eligible (12/20/10)

   - Patients with medical history or conditions not otherwise previously specified which
   in the opinion of the investigator should exclude participation in this study;
   examples of this would be: persistent gastrointestinal symptoms resulting from
   clostridia difficile enterocolitis or bowel surgery which may increase
   gastrointestinal toxicity from bevacizumab; or hearing loss or neuropathy which would
   prevent tolerance to cisplatin, and paclitaxel administration; the investigator should
   feel free to consult the Study Chair or Study Co-Chairs for uncertainty in this regard

   - Patients with metastatic tumor in the parenchyma of the liver or lungs with proximity
   to large vessels which could make the patient as high risk of lethal hemorrhage during
   treatment with bevacizumab (i.e. hemoptysis, liver rupture) (11/02/2009)


biological: bevacizumab

drug: carboplatin

drug: cisplatin

drug: paclitaxel

other: quality-of-life assessment

other: laboratory biomarker analysis

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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