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

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01652079

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

15.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer	Drug: CRLX101	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Mar 1, 2018

Actual Study Completion Date :

Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm CRLX101	Drug: CRLX101 q 14 days

Arm

Intervention/Treatment

Experimental: Treatment Arm

CRLX101

Drug: CRLX101

q 14 days

Outcome Measures

Primary Outcome Measures

Progression Free Survival [6 months]
Progression free survival at 6 months (PFS6) using RECIST 1.1

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02215
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

Principal Investigator: Richard Penson, MD, MRCP, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Richard Thomas Penson, Principal Investigator, Massachusetts General Hospital

ClinicalTrials.gov Identifier:

NCT01652079

Other Study ID Numbers:

11-485

First Posted:

Jul 27, 2012

Last Update Posted:

Jul 2, 2018

Last Verified:

Jun 1, 2018

Keywords provided by Richard Thomas Penson, Principal Investigator, Massachusetts General Hospital

Epithelial

Primary

Additional relevant MeSH terms:

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Study Results

No Results Posted as of Jul 2, 2018