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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

Phase 2
18 Years
Open (Enrolling)
Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Thank you

Trial Information

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



- To compare the progression-free survival hazard ratio in patients with persistent or
recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer treated with
bevacizumab with vs without everolimus.


- To determine the nature and degree of toxicity of these regimens.

- To compare the progression-free and overall survival of patients with measurable
disease vs those with detectable (non-measurable) disease.

- To estimate the proportion of patients with measurable disease who have objective tumor
response to treatment.

- To provide descriptive information about CA-125 response by regimen and, where
possible, by objective tumor response.

OUTLINE: This is a multicenter study. Patients are stratified according to their
platinum-free interval (≤ 182 days vs > 182 days), measurable disease status (measurable vs
non-measurable or "detectable" disease), and prior treatment with bevacizumab/aflibercept
(no vs yes). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral
everolimus once daily on days 1-28.

- Arm II: Patients receive bevacizumab as in arm I and oral placebo once daily on days

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.

Inclusion Criteria


- Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal

- Recurrent or persistent disease

- Meets 1 of the following criteria:

- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest dimension to be recorded) as ≥ 20 mm by chest x-ray OR as ≥
10 mm by spiral CT scan, MRI, or caliper measurement by clinical exam

- Must have ≥ 1 "target lesion" that can be used to assess response to study
treatment as defined by RECIST criteria

- 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 ≥ 90 days following completion of

- Lymph nodes must be ≥ 15 mm in short axis by CT scan or MRI

- Detectable disease, defined as non-measurable disease meeting ≥ 1 of the
following criteria:

- CA-125 ≥ 2 times upper limit of normal (ULN) at baseline

- Ascites and/or pleural effusion attributed to tumor

- Solid and/or cystic abnormalities on radiographic imaging that do not meet
RECIST criteria definitions for target lesions

- Must have received 1 prior platinum-based chemotherapeutic regimen that contained
carboplatin, cisplatin, or another organoplatinum compound for management of the
primary disease

- Initial treatment may have included intraperitoneal therapy, consolidation
therapy, non-cytotoxic therapy, or extended therapy administered after surgical
or non-surgical assessment

- Prior biologic (non-cytotoxic) therapy as part of the primary treatment regimen

- No prior non-cytotoxic therapy for management of recurrent or persistent

- Two additional prior cytotoxic regimens for management of recurrent or
persistent disease allowed (≤ 1 non-platinum, non-taxane regimen allowed)

- Patients who have received only one prior cytotoxic regimen (i.e.,
platinum-based regimen for management of primary disease) must have a
platinum-free interval of < 12 months OR have progressed during platinum-based
therapy OR have persistent disease after platinum-based therapy

- Not eligible for a higher priority GOG clinical trial (i.e., any active phase III GOG
protocol or Rare Tumor protocol for the same patient population)

- No history or evidence of CNS disease by physical exam, including primary brain tumor
or brain metastases


- GOG performance status (PS) 0-2 (for patients who have had 1 prior treatment)

- GOG PS 0-1 (for patients who have had 2 or 3 prior treatments)

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Creatinine ≤ 1.5 times ULN

- Bilirubin ≤ 1.5 times ULN

- SGOT ≤ 3.0 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- PT/INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if the patient is on a
stable dose of therapeutic warfarin for management of deep vein thrombosis, including
pulmonary embolism)

- PTT ≤ 1.5 times ULN

- Fasting serum cholesterol ≤ 300 mg/dL (or ≤ 7.75 mmol/L) AND fasting triglycerides ≤
300 mg/dL (or ≤ 3.42 mmol/L)

- Urine protein:creatinine ratio < 1.0

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other invasive malignancies within the past 3 years except nonmelanoma skin cancer

- No clinically significant cardiovascular disease, including any of the following:

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

- Myocardial infarction or unstable angina within the past 6 months

- NYHA class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication (asymptomatic, atrial
fibrillation with controlled ventricular rate allowed)

- Ejection fraction < 50% in patients who received prior treatment with an
anthracycline (including doxorubicin hydrochloride and/or liposomal doxorubicin

- Peripheral vascular disease ≥ CTCAE grade 2 (i.e., at least brief [< 24 hours]
episodes of ischemia managed non-surgically and without permanent deficit)

- Cerebrovascular accident or transient ischemic attack within the past 6 months

- No acute hepatitis or active infection requiring parenteral antibiotics (except for
uncomplicated urinary tract infection)

- No history or evidence of seizures not controlled with standard medical therapy

- No subarachnoid hemorrhage within the past 6 months

- No active bleeding or pathologic condition that carries a high risk of bleeding
(e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)

- No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess
within the past 28 days

- No clinical symptoms or signs of GI obstruction or requirement for parenteral
hydration and/or nutrition

- No serious non-healing wound, ulcer, or bone fracture

- No known hypersensitivity to murine or chimeric antibodies

- No other medical history or condition that, in the opinion of the investigator, would
preclude study participation


- See Disease Characteristics

- Recovered from prior surgery, radiotherapy, or chemotherapy

- No prior everolimus or any other mTOR inhibitor

- No prior cancer treatment that would contraindicate study therapy

- No 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
past 5 years

- Prior radiotherapy for localized cancer of the breast, head and neck, or skin
allowed provided it was completed > 3 years ago and the patient remains free of
recurrent or metastatic disease

- No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment
of ovarian, fallopian tube, or primary peritoneal cancer within the past 5 years

- Prior adjuvant chemotherapy for localized breast cancer allowed provided it was
completed > 3 years ago and the patient remains free of recurrent or metastatic

- For the purposes of this study, poly (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)

- At least 12 weeks since prior chimeric, human, or humanized monoclonal antibodies
(including bevacizumab) or VEGF receptor fusion protein (including aflibercept)

- More than 30 days since prior and no other concurrent investigational therapy

- More than 28 days since prior major surgery

- At least 3 weeks since any other prior therapy directed at the malignant tumor,
including biological or immunologic agents (small molecules or murine monoclonal

- At least 1 week since prior hormonal therapy directed at the malignant tumor

- No other concurrent anticancer agents

- No concurrent chronic treatment with systemic steroids or other immunosuppressive

- Concurrent warfarin allowed for prophylaxis or treatment of thrombosis

- Concurrent low molecular weight heparin allowed provided PT/INR is ≤ 1.5

- Concurrent low-dose aspirin (≤ 325 mg/day) allowed for patients at a higher risk for
arterial thromboembolic disease

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival hazard ratio

Safety Issue:


Principal Investigator

William P. Tew, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2010

Completion Date:

Related Keywords:

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cavity Cancer
  • recurrent ovarian epithelial cancer
  • recurrent fallopian tube cancer
  • recurrent primary peritoneal cavity cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial



Memorial Sloan Kettering Cancer Center New York, New York  10021
Cleveland Clinic Foundation Cleveland, Ohio  44195
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
Abington Memorial Hospital Abington, Pennsylvania  19001
Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Reading Hospital and Medical Center Reading, Pennsylvania  19612-6052
LDS Hospital Salt Lake City, Utah  84143
Rush University Medical Center Chicago, Illinois  60612-3824
Cedars-Sinai Medical Center Los Angeles, California  90048
Baystate Medical Center Springfield, Massachusetts  01199
Carolinas Medical Center Charlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
Iowa Methodist Medical Center Des Moines, Iowa  50309
Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
MetroHealth Medical Center Cleveland, Ohio  44109
Medical Oncology and Hematology Associates Des Moines, Iowa  50309
Saint Joseph Mercy Hospital Ann Arbor, Michigan  48106
AnMed Health Cancer Center Anderson, South Carolina  29621
Duke University Medical Center Durham, North Carolina  27710
Nebraska Methodist Hospital Omaha, Nebraska  68114
Case Western Reserve University Cleveland, Ohio  44106
Riverside Methodist Hospital Columbus, Ohio  43214
Indiana University Medical Center Indianapolis, Indiana  46202
Providence Saint Joseph Medical Center Burbank, California  91505-4866
Hillcrest Hospital Cancer Center Mayfield Heights, Ohio  44124
The Hospital of Central Connecticut New Britain, Connecticut  06050
McFarland Clinic Ames, Iowa  50010
Iowa Oncology Research Association CCOP Des Moines, Iowa  50309
Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des Moines Des Moines, Iowa  50309
Saint John's Hospital Springfield, Missouri  65804
Cox Medical Center Springfield, Missouri  65807
Cooper Hospital University Medical Center Camden, New Jersey  08103
University of California Medical Center At Irvine-Orange Campus Orange, California  92868
Cancer Care Associates-Yale Tulsa, Oklahoma  74136-1929
Women and Infants Hospital Providence, Rhode Island  02905
Lake University Ireland Cancer Center Mentor, Ohio  44060
University of Colorado Cancer Center - Anschutz Cancer Pavilion Aurora, Colorado  80045
Gynecologic Oncology Group of Arizona Phoenix, Arizona  85012
Sudarshan K Sharma MD Limted-Gynecologic Oncology Hinsdale, Illinois  60521
Saint Vincent Oncology Center Indianapolis, Indiana  46260
Carle Foundation - Carle Cancer Center Urbana, Illinois  61801
Cleveland Clinic Cancer Center/Fairview Hospital Cleveland, Ohio  44111
Baylor All Saints Medical Center at Fort Worth Fort Worth, Texas  76104