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

Triple-Negative Breast Carcinoma Clinical Trial

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 Cancer

Status Active, not recruiting

Clinical Trial 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 (recurrent). 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 be safe, tolerable and/or effective in treating patients with recurrent ovarian, fallopian tube, or peritoneal cancer or recurrent triple-negative breast cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Assess the maximum tolerated dose (MTD) of cediranib maleate (cediranib) 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) 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 of cediranib and olaparib (tablet formulation) when administered in combination. (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)

TRANSLATIONAL OBJECTIVES:

I. To evaluate the prognostic and predictive role of measured changes in functional vascular imaging using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) between pre-study and day 3. (Phase II) II. To evaluate in an exploratory fashion the predictive or prognostic value of single nucleotide polymorphisms (SNPs) in key genes involved in angiogenesis and deoxyribonucleic acid (DNA) repair. (Phase II) III. To evaluate the predictive value of baseline peripheral blood mononuclear cells (PBMC) poly adenosine diphosphate (ADP) ribose (PAR) incorporation on response to therapy. (Phase II) IV. To measure early changes in vascular cytokine production and evaluate in an exploratory fashion that these changes may be predictive or prognostic, or differentially affected by the combination of agents. (Phase II) V. To evaluate early changes to circulating endothelial cells and if these changes are predictive or prognostic. (Phase II) VI. To assess changes in measures of DNA damage and repair and angiogenesis in tumor cells (tissue and/or malignant effusions) and correlate to drug/drug/combination. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a randomized phase II study.

PHASE I: Patients receive cediranib maleate orally (PO) once daily (QD) and olaparib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and as clinically indicated on study. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) as well as blood sample collection on the trial. Patients may also optionally undergo a tissue biopsy on the trial.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cediranib maleate PO QD and olaparib PO BID on days 1-28.

ARM II: Patients receive olaparib PO BID on days 1-28.

In both arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo CT or MRI as well as blood sample collection on the trial. Patients may also optionally undergo a tissue biopsy on the trial.

After completion of study treatment, patients are followed up every 6 months for up to 3 years. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Papillary
• Breast Neoplasms
• Carcinoma
• Carcinoma, Endometrioid
• Fallopian Tube Carcinoma
• Ovarian Endometrioid Adenocarcinoma
• Ovarian Serous Adenocarcinoma
• Ovarian Serous Surface Papillary Adenocarcinoma
• Primary Peritoneal Serous Adenocarcinoma
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Carcinoma

• NCT number: NCT01116648
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 14, 2010
• Completion date: February 13, 2025