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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
N/A
Open (Enrolling)
Female
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


OBJECTIVES:

Primary

- 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.

Secondary

- 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
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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

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

- 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
radiotherapy

- 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
allowed

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

- 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

PATIENT CHARACTERISTICS:

- 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
hydrochloride)

- 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

PRIOR CONCURRENT THERAPY:

- 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
disease

- 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
antibodies)

- 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
agents

- 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:

Interventional

Study Design:

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

Outcome Measure:

Progression-free survival hazard ratio

Safety Issue:

No

Principal Investigator

William P. Tew, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

GOG-0186G

NCT ID:

NCT00886691

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

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Cleveland Clinic FoundationCleveland, Ohio  44195
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Abington Memorial HospitalAbington, Pennsylvania  19001
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
LDS HospitalSalt Lake City, Utah  84143
Rush University Medical CenterChicago, Illinois  60612-3824
Cedars-Sinai Medical CenterLos Angeles, California  90048
Baystate Medical CenterSpringfield, Massachusetts  01199
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
MetroHealth Medical CenterCleveland, Ohio  44109
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
AnMed Health Cancer CenterAnderson, South Carolina  29621
Duke University Medical CenterDurham, North Carolina  27710
Nebraska Methodist HospitalOmaha, Nebraska  68114
Case Western Reserve UniversityCleveland, Ohio  44106
Riverside Methodist HospitalColumbus, Ohio  43214
Indiana University Medical CenterIndianapolis, Indiana  46202
Providence Saint Joseph Medical CenterBurbank, California  91505-4866
Hillcrest Hospital Cancer CenterMayfield Heights, Ohio  44124
The Hospital of Central ConnecticutNew Britain, Connecticut  06050
McFarland ClinicAmes, Iowa  50010
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Saint John's HospitalSpringfield, Missouri  65804
Cox Medical CenterSpringfield, Missouri  65807
Cooper Hospital University Medical CenterCamden, New Jersey  08103
University of California Medical Center At Irvine-Orange CampusOrange, California  92868
Cancer Care Associates-YaleTulsa, Oklahoma  74136-1929
Women and Infants HospitalProvidence, Rhode Island  02905
Lake University Ireland Cancer CenterMentor, Ohio  44060
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
Gynecologic Oncology Group of ArizonaPhoenix, Arizona  85012
Sudarshan K Sharma MD Limted-Gynecologic OncologyHinsdale, Illinois  60521
Saint Vincent Oncology CenterIndianapolis, Indiana  46260
Carle Foundation - Carle Cancer CenterUrbana, Illinois  61801
Cleveland Clinic Cancer Center/Fairview HospitalCleveland, Ohio  44111
Baylor All Saints Medical Center at Fort WorthFort Worth, Texas  76104