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Recurrent Fallopian Tube CarcinomaPhase 2NCT00886691

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

A Phase 2 study testing Bevacizumab, Everolimus and Laboratory Biomarker Analysis in people with Recurrent Fallopian Tube Carcinoma and Recurrent Ovarian Carcinoma, run by GOG Foundation at 45 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Bevacizumab, Everolimus and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
150 participants
Where
45 sitesUnited States
Study dates
27 Dec 2010to 23 Mar 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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound' this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment
  • Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum, non-taxane regimen
  • Patients are allowed to receive, but are not required to receive, biologic (non-cytotoxic) therapy as part of their primary treatment regimen; patients must have NOT received any non-cytotoxic therapy for management of recurrent or persistent disease
  • Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
  • For the purposes of this study, poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors will be considered ?cytotoxic,? and prior treatment with PARP inhibitors for primary or recurrent disease WILL be allowed (either alone or in combination with chemotherapy)
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
  • Platelets greater than or equal to 100,000/mcl
  • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
  • Bilirubin less than or equal to 1.5 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3 x ULN
  • Alkaline phosphatase less than or equal to 2.5 x ULN
  • Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 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 for management of deep vein thrombosis including pulmonary embolism)
  • Partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal
  • Fasting serum cholesterol less than or equal to 300 mg/dL OR less than or equal to 7.75 mmol/L AND
  • Fasting triglycerides less than or equal to 300 mg/dL or 3.42 mmol/L
  • Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended; UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion?a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
  • Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception
  • Patients must have signed an approved informed consent and authorization permitting the release of personal health information
  • Patients must meet pre-entry requirements
  • Patients with clinically significant cardiovascular disease; this includes:
  • Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg
  • Myocardial infarction or unstable angina within 6 months prior to registration
  • New York Heart Association (NYHA) class II or greater congestive heart failure
  • Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate
  • Patients who have received prior treatment with an anthracycline (including doxorubicin and or liposomal doxorubicin) and have an ejection fraction < 50%
  • Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater peripheral vascular disease (at least brief [< 24 hours (hrs)] episodes of ischemia managed non-surgically and without permanent deficit)

Who cannot join

  • 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
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  • 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
  • Known or suspected past hepatitis B infection
  • Known or suspected past hepatitis C infection (including past interferon ?curative? treatment)
  • Blood transfusion(s) prior to 1990
  • Current or prior IV drug use
  • Current or prior dialysis
  • Household contact with hepatitis B or hepatitis C infected person(s)
  • Current or prior high-risk sexual activity
  • Body piercing or tattoos
  • Mother known to have hepatitis B
  • History suggestive of hepatitis B infection, e.g., dark urine, jaundice, right upper quadrant pain

Trial locations and contacts

45 sites in 1 country.

45 sites in 1 country

United States45 sites

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • McFarland Clinic PC - Ames

    Ames, Iowa, 50010

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Iowa-Wide Oncology Research Coalition NCORP

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Laurel

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Baylor All Saints Medical Center at Fort Worth

    Fort Worth, Texas, 76104

  • Sudarshan K Sharma MD Limited-Gynecologic Oncology

    Hinsdale, Illinois, 60521

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Saint Vincent Hospital and Health Care Center

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Gynecologic Oncology Group of Arizona

    Phoenix, Arizona, 85012

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Oklahoma Cancer Specialists and Research Institute-Tulsa

    Tulsa, Oklahoma, 74146

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Reading Hospital

    West Reading, Pennsylvania, 19611

Other trials in United States

About this study

Official title: A Phase II Randomized, Double-Blinded Evaluation of Oral Everolimus (RAD001) Plus Bevacizumab vs. Oral Placebo Plus Bevacizumab in the Treatment of Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the progression-free survival hazard ratio of the combination of oral everolimus (RAD001) and bevacizumab compared to oral placebo and bevacizumab in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.

SECONDARY OBJECTIVES:

  1. To determine the nature and degree of toxicity of oral everolimus (or placebo) plus bevacizumab.

II. To characterize and compare progression-free survival and overall survival in patients with measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] criteria) and patients with detectable (non-measurable) disease.

III. To estimate the proportion of patients with measurable disease who have objective tumor responses by treatment.

IV. To provide descriptive information about cancer antigen (CA)-125 responses by regimen and where possible by objective tumor responses.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and everolimus orally (PO) once daily (QD) on days 1-28.

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

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Being tested
Bevacizumab, Everolimus, Laboratory Biomarker Analysis, Placebo
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • EverolimusDrug

    Also called 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PlaceboOther

    Also called placebo therapy, PLCB, sham therapy

    Given PO

Study groups in NCT00886691
Study groupRoleWhat they receive
Arm I (bevacizumab and everolimus)ExperimentalPatients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and everolimus PO QD on days 1-28.
Receives: Biological: Bevacizumab; Drug: Everolimus; Other: Laboratory Biomarker Analysis
Arm II (bevacizumab and placebo)ExperimentalPatients receive bevacizumab as in Arm I and placebo PO QD on days 1-28.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

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

    Number of participants with a grade of 3 or higher during the treatment period.

    Measured: 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.

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

    Progression-free survival and overall survival broken down by measurable disease status

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

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

    Complete and Partial Tumor Response by RECIST 1.0

    Measured: Up to approximately 4 years and 6 months

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

    Response as evaluated by CA-125 levels.A CA 125 test measures the amount of the protein CA 125 (cancer antigen 125) in blood.CA 125 is a tumor marker recommended for clinical use in the diagnosis and management of ovarian cancer. CA-125 responses were assessed with Rustin criteria. Initial values had to be 2x ULN (upper limit of normal) within 2 weeks of starting therapy to be considered evaluable.Patient were evaluated by using best overall response while receiving study therapy.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2009 (estimated)
  2. Study start27 Dec 2010
  3. Primary completion27 Jun 2014
  4. Study completion23 Mar 2015

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00886691
Sponsor's protocol ID
GOG-0186G
Other IDs
NCI-2011-01914, CDR0000640439, GOG-0186G, GOG-0186G, U10CA180868, U10CA027469
Status last verified
Jan 2022
First submitted
22 Apr 2009
Last updated
4 Feb 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 37185961

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Everolimus and Laboratory Biomarker Analysis in people with Recurrent Fallopian Tube Carcinoma and Recurrent Ovarian Carcinoma, run by GOG Foundation at 45 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 41 inclusion and 25 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 4 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 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 2 Jul 2018). 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?

Progression-free Survival (time frame: Duration of time from start of treatment to time of progression, approximately 4 years and 6 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00886691, which also lists 1 linked publication.

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 4 Feb 2022.

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