Study of Revlimid With Doxil and Avastin for Patients With Platinum Resistant Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

Phase IB Study of Lenalidomide (Revlimid®) With Liposomal Doxorubicin (Doxil®) and Bevacizumab (Avastin®) for Patients With Platinum Resistant Ovarian Cancer.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01202890
• Other study ID #: INST 1001
• Status: Terminated
• Phase: Phase 1
• First received: September 14, 2010
• Last updated: January 7, 2014
• Start date: September 2010
• Est. completion date: May 2012

Study information

• Verified date: January 2014
• Source: New Mexico Cancer Care Alliance
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: May 2012
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Epithelial Ovarian Cancer
• Fallopian Tube Carcinoma
• Fallopian Tube Neoplasms
• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms
• Primary Peritoneal Carcinoma

Intervention

Drug:
• Lenalidomide, Liposomal Doxorubicin, Bevacizumab
At the expansion phase: Revlimid 20 mg (days 1-21), Doxil 30 mg/m2 on Day 1 and Avastin 15 mg/kg on Day 1, every 3 weeks. If this regimen is not cumulatively tolerable, Avastin will be administered every other course. Patients will be received up to 6 cycles or disease progression, followed by Revlimid maintenance at 25 mg PO q Day for 3 weeks every 4 weeks in patients with stable disease.
• Revlimid, Doxil, Avastin
At the expansion phase: Revlimid 20 mg (days 1-21), Doxil 30 mg/m2 on Day 1 and Avastin 15 mg/kg on Day 1, every 3 weeks. If this regimen is not cumulatively tolerable, Avastin will be administered every other course. Patients will be received up to 6 cycles or disease progression, followed by Revlimid maintenance at 25 mg PO q Day for 3 weeks every 4 weeks in patients with stable disease.

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico

Sponsors (2)

Lead Sponsor	Collaborator
New Mexico Cancer Care Alliance	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of the 3 drug combination and recommend a dose for phase II studies.		6-8 months	No
Secondary	Progression-free survival (PFS) after treatment with Revlimid plus Avastin and Doxil.		6-8 Months	No
Secondary	Acute and subacute toxicities of Lenalidomide plus Doxil and Avastin for the treatment of ovarian cancer.		6-8 Months	Yes