Bevacizumab With or Without Everolimus in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

NCT00886691 | Completed Phase 2 Results DMC

• 5 other identifiers: GOG-0186GNCI-2011-01914CDR0000640439U10CA180868U10CA027469
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 45

Brief Summary

This randomized phase II trial studies how well bevacizumab with or without everolimus works in treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and everolimus may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without everolimus in treating ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

Conditions

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as an 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Duration of time from start of treatment to time of progression, approximately 4 years and 6 months.

Secondary Outcomes (4)

• Incidence of Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0)

  All Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during treatment and up to 30 days after stopping the study treatment, approximately 4 years and 6 months.

• Characterize and Compare Progression-free Survival and Overall Survival in Patients With Measurable Disease (RECIST Criteria) and Patients With Detectable (Non-measurable) Disease

  Continued until disease progression, assessed up to approximately 4 years and 6 months

• The Proportion of Patients With Measurable Disease Who Have Objective Tumor Responses by Treatment.

  Up to approximately 4 years and 6 months

• Percentage of Participants With at Least One Cancer Antigen 125 (CA-125) Response

  Prior to each cycle of treatment. Then follow-up every three months for 2 years , then every 6 months for 3 years. Duration was approximately 4 years and 6 months.

Study Arms (2)

Arm I (bevacizumab and everolimus)

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and everolimus PO QD on days 1-28.

Biological: Bevacizumab; Drug: Everolimus; Other: Laboratory Biomarker Analysis

Arm II (bevacizumab and placebo)

EXPERIMENTAL

Patients receive bevacizumab as in Arm I and placebo PO QD on days 1-28.

Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Placebo

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Arm I (bevacizumab and everolimus); Arm II (bevacizumab and placebo)

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Arm I (bevacizumab and everolimus)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (bevacizumab and everolimus); Arm II (bevacizumab and placebo)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (bevacizumab and placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report
• Patients must have measurable disease or detectable (non-measurable) disease:
• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be greater than or equal to 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray; lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI
• Detectable disease in a patient is defined as one who does not have measurable disease but has at least one of the following conditions:
• Baseline values of CA-125 at least 2 x upper limit of normal (ULN)
• Ascites and/or pleural effusion attributed to tumor
• Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions
• Patients in the measurable disease cohort must have at least one ?target lesion? to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as ?non-target? lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III protocol or Rare Tumor Protocol for the same patient population
• Patients who have had one prior treatment must have a GOG performance status of 0, 1, or 2; patients who have had two or three prior treatments must have a GOG performance status of 0 or 1
• Patients should be free of active infection requiring parenteral antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
• Recovery from effects of recent surgery, radiotherapy, or chemotherapy
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• Any other prior therapy directed at the malignant tumor, including biological and immunologic agents, must be discontinued at least 3 weeks prior to registration (including small molecules and murine monoclonal antibodies); chimeric or human or humanized monoclonal antibodies (including bevacizumab) or vascular endothelial growth factor (VEGF) receptor fusion protein (including VEGF Trap, aflibercept) must be discontinued for at least 12 weeks prior to registration; no investigational therapy within 30 days prior to the first date of study treatment
• Prior therapy:

You may not qualify if:

• Patients who have received prior everolimus or any other mammalian target of rapamycin (mTOR) inhibitor
• Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years 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 OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years 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 the patient remains free of recurrent or metastatic disease
• 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 prior to the first date of study treatment
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, 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 prior to the first date of study treatment
• Known hypersensitivity to murine or chimeric antibodies
• Major surgery within 28 days prior to the first date of study treatment
• Patients with clinical symptoms or signs of gastrointestinal obstruction and patients who require parenteral hydration and/or nutrition
• Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator can consult the Study Chair or Study Co-Chairs for uncertainty in this regard
• Patients who are pregnant or nursing
• Patients with active hepatitis B or C
• Laboratory confirmation to exclude hepatitis B and C is required in any patient considered at high risk for hepatitis B or C; risk factors can include:
• You currently live in (or have lived in) Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, and Greece

Sponsors & Collaborators

• GOG Foundation: lead
• National Cancer Institute (NCI): collaborator

Study Sites (45)

Gynecologic Oncology Group of Arizona

Phoenix, Arizona, 85012, United States

Location

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Sudarshan K Sharma MD Limited-Gynecologic Oncology

Hinsdale, Illinois, 60521, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

McFarland Clinic PC - Ames

Ames, Iowa, 50010, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Laurel

Des Moines, Iowa, 50314, United States

Location

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

CoxHealth South Hospital

Springfield, Missouri, 65807, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, 44124, United States

Location

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, 44060, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, 74146, United States

Location

Jefferson Abington Hospital

Abington, Pennsylvania, 19001, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

AnMed Health Cancer Center

Anderson, South Carolina, 29621, United States

Location

Baylor All Saints Medical Center at Fort Worth

Fort Worth, Texas, 76104, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Everolimus

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Sirolimus; Macrolides; Lactones

Results Point of Contact

• Title: Linda Gedeon for Michael Sill, PhD.
• Organization: NRG Oncology

lgedeon@gogstats.org

716-845-1169

Study Officials

• William P Tew

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2009
• First Posted: April 23, 2009
• Study Start: December 27, 2010
• Primary Completion: June 27, 2014
• Study Completion: March 23, 2015
• Last Updated: February 4, 2022
• Results First Posted: July 2, 2018

Record last verified: 2022-01

Locations

US (45)