Clinical trial NCT01202890: Study of Revlimid With Doxil and Avastin for Patients With Platinum Resistant Ovarian Cancer
Official title: Phase IB Study of Lenalidomide (Revlimid®) With Liposomal Doxorubicin (Doxil®) and Bevacizumab (Avastin®) for Patients With Platinum Resistant Ovarian Cancer.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Ovarian Cancer
Epithelial Ovarian Cancer
Fallopian Tube Carcinoma
Primary Peritoneal Carcinoma
Keywords: lenalidomide
revlimid
liposomal doxorubicin
doxil
bevacizumab
avastin
platinum resistant ovarian cancer
ovarian cancer
Lead sponsor: New Mexico Cancer Research Alliance
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2010-09-16
Enrollment: 1
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will test the feasibility of combining 3 drugs, Revlimid with Doxil and Bevacizumab,and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.

Detailed description: The combination of Doxil with Avastin has several aspects of interest to ovarian cancer treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is possible tumoral interstitial pressure via increased half-life (if liposomal egress is diminished) and decreased \[42\], 3) improved Doxil distribution, and 4) likely favorable toxicity profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar erythrodysesthesia or PPE). Lenalidomide has also antiangiogenic properties, with a different mechanism of action than Avastin. Given the preliminary results of the effect of the combination of Doxil with Avastin, showing an increase in progression-free survival, we are interested in using a new thalidomide analog to maximize the angiogenic inhibition. This study will test the feasibility of combining all 3 drugs, and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.

Eligibility criteria: Inclusion Criteria:

* EOC patients must be platinum resistant/refractory (see 1.1 for definition) and be considered by the attending physician capable of being treated in this study according to GCP.
* Measurable disease by RECIST criteria or evaluable disease by GCIC criteria
* No prior anthracycline or lenalidomide use, unless the dose received was equal or less than one cycle and the patient did not progress on treatment.
* Subjects must have calculated creatinine clearance \> 60ml/min by Cockcroft-Gault formula during the escalation phase.
* Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula during the expansion phase. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance \> 30ml/min and \< 60ml/min.
* Understand and voluntarily sign an informed consent form.
* All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
* Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
* No contraindication to anticoagulation

Exclusion Criteria:

* Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
* Concurrent use of other anti-cancer agents or treatments.
* Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
* History of thromboembolic event within the last 3 months
* Known hypersensitivity to any component of Avastin

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of the 3 drug combination and recommend a dose for phase II studies.
timeFrame: 6-8 months
Secondary outcomes:
measure: Progression-free survival (PFS) after treatment with Revlimid plus Avastin and Doxil.
timeFrame: 6-8 Months
measure: Acute and subacute toxicities of Lenalidomide plus Doxil and Avastin for the treatment of ovarian cancer.
timeFrame: 6-8 Months
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
Study officials:
affiliation: University of New Mexico
name: Teresa Rutledge, MD
role: PRINCIPAL_INVESTIGATOR
References: