CRLX101 in Combination With Bevacizumab for Recurrent Ovarian/Tubal/Peritoneal Cancer

A Phase II, 2-stage Trial of CRLX101 in Combination With Bevacizumab in Recurrent Platinum-Resistant Ovarian, Tubal and Peritoneal Cancer

This research study is a Phase II clinical trial. In addition to studying safety, Phase II clinical trials test if the investigational drug is effective and whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved CRLX101 for your type of cancer.

Camptothecin is a chemical extracted from plants that is the basis for the standard FDA-approved chemotherapy drugs irinotecan and topotecan. Camptothecin works by interfering with the way cells divide and multiply. The investigational drug CRLX101 is a formulation of camptothecin and a large molecule (nanoparticle)that appears to allow more of the camptothecin to get into tumors and stay in tumors. The persistence of the CRLX101 in the tumor may increase the probability that the tumor cells will be damaged.

CRLX101 has been well tolerated in the laboratory and in participants with different kinds of cancer.

Bevacizumab (Avastin) is a VEGF inhibitor which has activity in many kinds of cancer. Bevacizumab has been successfully combined with many chemotherapy partners.

It has been hypothesized that the combination of bevacizumab with CRLX101 might have unique clinical activity in combination in the treatment of this disease due to the simultaneous inhibition of distinct steps along the HIF → (CAIX) → VEGF → VEGFR2 pathway. Specifically, it is hypothesized that CRLX101-mediated inhibition of HIF-1α carries with it the potential to interrupt hypoxia and HIF-1α-associated resistance to VEGFR inhibitors. It is hoped that this combination will work to treat your type of cancer.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
• Intervention / Treatment: Drug: CRLX101

Detailed Description

You will receive CRLX101 and bevacizumab through an intravenous (IV) infusion once every 14 days. Each cycle is 28 days. You will continue to receive both drugs until you and/or the research doctor decides it may not be in your best interest to continue.

You will receive premedication including decadron, zantac and benadryl to help prevent an allergic reaction and nausea prior to your CRLX101 infusion.You will also receive IV fluid before and after the study drug administration to keep you hydrated. It will be important for you to drink water regularly in between study visits.You will be treated as an outpatient. At every clinic visit, you will undergo the following assessments: Medical history, physical examination, vital signs, performance status, routine blood tests, urine tests, assessment for any new side effects, CT evaluation (every 8 weeks).

You will have an end of study visit within 30 days of your last dose.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically or cytologically confirmed epithelial ovarian, tubal or primary peritoneal cancer
• Measurable disease
• May have received up to 2 prior cytotoxic chemotherapy
• Life expectancy of greater than 3 months

Exclusion Criteria:

• Pregnant or breastfeeding
• Prior camptothecin, prior VEFG inhibitors
• Gross hematuria
• Chemotherapy or radiotherapy within 4 weeks of study entry
• uncontrolled HTN
• Receiving other study agents
• History of allergic reaction to compounds of similar chemical or biologic composition to topotecan or irinotecan
• Known brain metastases
• History of a different malignancy within the previous 2 years
• Intercurrent illness
• HIV positive on combination antiretroviral therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; CRLX101	Drug: CRLX101; q 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression free survival at 6 months (PFS6) using RECIST 1.1	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response Rate (CR+PR) using RECIST 1.1	2 years
Assessment of Toxicity	Assessment of toxicity	2 years
Analysis of biopsies	Analysis of ovarian tumor biopsies and ascites of the presence or absence of CRLX101 or the active drug, camptothecin	2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Richard Penson, MD, MRCP, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimate): July 27, 2012

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: June 28, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Primary; Epithelial
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Peritoneal Diseases; Genital Neoplasms, Female; Adnexal Diseases; Digestive System Neoplasms; Fallopian Tube Diseases; Abdominal Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms
• Other Study ID Numbers: 11-485

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No