Clinical Trial: Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I/II Study of Cediranib and Olaparib in Combination for Treatment of Recurrent Papillary-Serous Ovarian, Fallopian Tube, or Peritoneal Cancer or for Treatment of Recurrent Triple-Negative Breast

Brief Summary: This partially randomized phase I/II trial studies the side effects and the best dose of cediranib maleate and olaparib and to see how well they work compared to olaparib alone in treating patients with ovarian, fallopian tube, peritoneal, or triple-negative breast cancer that has returned after a period of improvement. Cediranib maleate may help keep cancer cells from growing by affecting their blood supply. Olaparib may stop cancer cells from growing abnormally. The combination of cediranib maleate and olaparib may help to keep cancer from growing.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Assess the maximum tolerated dose (MTD) of cediranib (cediranib maleate) in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. (Phase I) II. Assess the efficacy (as measured by progression-free survival [PFS]) of the combination of cediranib and olaparib compared to olaparib alone in recurrent grade 2 or 3 platinum-sensitive papillary-serous or endometrioid ovarian, fallopian tube, or peritoneal cancer. (Phase II) III. Assess the MTD of cediranib in combination with olaparib tablet formulation in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer. (Phase I-T)

SECONDARY OBJECTIVES:

I. Assess the toxicities of the combination of cediranib and olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. (Phase I) II. Assess clinical benefit, progression-free survival, and overall survival for patients treated with cediranib and olaparib. (Phase I) III. Assess tumor response, clinical response benefit (response or stable disease as defined by Response Evaluation Criteria in Solid Tumors [RECIST] response criteria x 16 weeks), and overall survival (OS) for patients treated with cediranib and olaparib at the recommended phase II dose (RP2D) as compared with patients receiving olaparib alone. (Phase II) IV. Assess the toxicities of the combination of cediranib and olaparib (tablet formulation) in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer. (Phase I-T) V. Assess clinical benefit, progression-free survival, and overall survival for patients treated with cediranib and olaparib (tablet formulation). (Phase I-T) VI. Assess the pharmacokinetic profile
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Dose limiting toxicities and maximum tolerated dose of cediranib maleate in combination with olaparib (tablet formulation) (Phase I-Tablet) [ Time Frame: At 28 days ]
    Will be determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
  • Dose limiting toxicity and maximum tolerated dose of cediranib maleate in combination with olaparib (Phase I) [ Time Frame: At 28 days ]
    Will be determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
  • Progression-free survival at the maximum tolerated dose/recommended phase 2 dose of cediranib maleate with olaparib compared to that of olaparib alone (Phase II) [ Time Frame: Time from start of treatment to time of objective disease progression, assessed up to 3 years ]
    Will be evaluated by Kaplan-Meier analysis and log-rank test for between group comparison, and median survival times reported.


Original Primary Outcome:

  • Phase I: Establish the MTD of cediranib in combination with olaparib in the treatment of recurrent papillary-ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. [ Time Frame: 2 years ]
  • Phase II: Assess the efficacy of the combination of cediranib and olaparib compared to cediranib alone in recurrent grade 2 or 3 platinum-sensitive papillary-serous ovarian, fallopian tube, or peritoneal cancer, as measured by disease-free progression. [ Time Frame: 2 years ]


Current Secondary Outcome:

  • Clinical benefit rate defined as response or stable disease x 16 weeks, as determined by Response Evaluation Criteria in Solid Tumors 1.1 criteria (Phase II) [ Time Frame: Up to 3 years ]
    Will be determined by Response Evaluation Criteria in Solid Tumors 1.1 criteria.
  • Incidence of toxicities of the combination of cediranib maleate and olaparib (Phase I) [ Time Frame: Up to 3 years ]
    Will be determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
  • Incidence of toxicities of the combination of cediranib maleate and olaparib (Phase I-Tablet) [ Time Frame: Up to 3 years ]
    Will be determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
  • Overall survival (Phase II) [ Time Frame: Up to 3 years ]
    Will be evaluated by Kaplan-Meier analysis and log-rank test for between-group comparison, and median survival time will be reported.
  • Tumor response rate as defined by Response Evaluation Criteria in Solid Tumors criteria (Phase II) [ Time Frame: Up to 3 years ]
    The response rates will be compared by an exact test and 95% confidence intervals will also be reported.


Original Secondary Outcome:

  • Phase I: Assess side effects and toxicity of this drug combination in this patient population, as measured by CTCAE Active Version. [ Time Frame: 2 years ]
    The type and number of participants with adverse events will be assessed as a measure of safety and tolerability
  • Phase I: Assess clinical benefit, progression-free survival, and overall survival for this patient population. [ Time Frame: 5 years ]
  • Phase II: Assess tumor response, clinical response benefit, and overall survival for patients treated with cediranib and olaparib as compared with patients receiving olaparib alone. [ Time Frame: 5 years ]


Information By: National Cancer Institute (NCI)

Dates:
Date Received: April 29, 2010
Date Started: March 2010
Date Completion:
Last Updated: May 23, 2017
Last Verified: May 2017