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Clinical Trial 19856

Cancer Type: Gynecological Tumor
Interventions:AMP-514 (Durvalumab); Avastin (Bevacizumab); Bevacizumab; Durvalumab; MEDI4736 (Durvalumab); Olaparib (Lynparza); Paraplatin (carboplatin); Placebo; Taxol (paclitaxel); carboplatin; paclitaxel

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Robert Wenham

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase III Randomised, Double-Blind, Placebo-Controlled,Multicentre Study of Durvalumab in Combination with Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).

Summary

Objective

Primary Objective: To determine the efficacy of durvalumab and olaparib assessed by PFS in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. Secondary Objectives: To determine the efficacy of durvalumab and olaparib assessed by OS in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. To assess the efficacy of durvalumab and olaparib in combination with platinum-based chemotherapy and bevacizumab in terms of PFS2, ORR, ORR presurgery in IDS group, duration of response, TFST, TSST and TDT in the first line treatment of nontBRCAm patients with newly diagnosed advanced ovarian cancer. To determine the effects on HRQoL, global health status and ovarian cancer symptoms of the combination of durvalumab and olaparib in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer.To determine the effects on pCR for the combination of durvalumab and olaparib in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. To characterize the PK and immunogenicity of durvalumab in combination with bevacizumab and olaparib. To determine olaparib plasma concentrations via sparse sampling for population PK analyses. To assess the potential additional clinical benefit of durvalumab added to SoC and olaparib in the first line treatment of tBRCAm patients with newly diagnosed advanced ovarian cancer. Safety Objectives: To evaluate the safety and tolerability of the combination of durvalumab and bevacizumab given in combination with platinum based chemotherapy and continued as maintenance in patients with newly diagnosed advanced ovarian cancer. To evaluate the safety and tolerability of durvalumab in combination with platinum based chemotherapy+/- bevacizumab and continued as maintenance in combination with olaparib +/-bevacizumab in patients with newly diagnosed advanced ovarian cancer.

Inclusion Criteria

  • Female participants with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer
  • Participants must be aged ≥18 years of age. For participants enrolled in Japan that are aged >All participants should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery
  • Evidence of presence or absence of BRCA1/2 mutation in tumour tissue
  • Mandatory provision of tumour sample for centralised tBRCA testing
  • ECOG performance status 0-1
  • Participants must have preserved organ and bone marrow function
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test

  • Exclusion Criteria

  • Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology
  • Prior systemic anti-cancer therapy for ovarian cancer
  • Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation
  • Prior treatment with PARP inhibitor or immune mediated therapy
  • Planned intraperitoneal cytotoxic chemotherapy
  • Active or prior documented autoimmune or inflammatory disorders
  • Participants considered a poor medical risk due to a serious, uncontrolled intercurrent illness
  • Clinically significant cardiovascular disease
  • Participants with known brain metastases
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (participants who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease)
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2
  • Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy
  • Participants with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents
  • Breast feeding women