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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Carolyn N. Krasner, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01652079
First received: July 25, 2012
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Drug: CRLX101
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Progression free survival at 6 months (PFS6) using RECIST 1.1


Secondary Outcome Measures:
  • Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Response Rate (CR+PR) using RECIST 1.1

  • Assessment of Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Assessment of toxicity

  • Analysis of biopsies [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Analysis of ovarian tumor biopsies and ascites of the presence or absence of CRLX101 or the active drug, camptothecin


Estimated Enrollment: 29
Study Start Date: April 2012
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
CRLX101
Drug: CRLX101
q 14 days

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01652079

Contacts
Contact: Carolyn Krasner, MD 6177244800 cnkrasner@partners.org

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Pangiotis Konstantinopolous, MD    617-667-9259    pkonstan@bidmc.harvard.edu   
Principal Investigator: Pangiotis Konstantinopolous, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Susana Campos, MD    617-724-3858    scampos@partners.org   
Principal Investigator: Susana Campos, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Susana Campos, MD    617-724-3858    scampos@partners.org   
Principal Investigator: Susana Campos, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Carolyn Krasner, MD    617-726-1941    cnkrasner@partners.org   
Contact: Christina Illiano, RN    617 643-5050    cilliano@partners.org   
Principal Investigator: Carolyn Krasner, MD         
Sponsors and Collaborators
Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Carolyn N. Krasner, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01652079     History of Changes
Other Study ID Numbers: 11-485
Study First Received: July 25, 2012
Last Updated: January 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Epithelial
Primary

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014