A Study to Evaluate the Effectiveness and Tolerability of a Second Maintenance Treatment in Participants With Ovarian Cancer, Who Have Previously Received Polyadenosine 5'Diphosphoribose [Poly (ADP Ribose)] Polymerase Inhibitor (PARPi) Treatment.

NCT04239014 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: D6018C00004
• Study Type: interventional
• Target: N/A
• Locations: 4 countries
• Sites: 26

Brief Summary

To investigate the effectiveness and tolerability of a second maintenance treatment in participants with platinum-sensitivity relapsed (PSR) epithelial ovarian cancer, who have previously received PARPi maintenance treatment and who have benefit (complete response \[CR\] or partial response \[PR\]) or stable disease (SD) from further platinum based chemotherapy.

Conditions

Ovarian Cancer

Keywords

Platinum Sensitive Relapsed Epithelial Ovarian Cancer; Polyadenosine 5'diphosphoribose (poly [ADP ribose]) polymerase inhibitor (PARPi)

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  To assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo.

  To assess from the time of randomization until the date of objective disease progression or death (by any cause in the absence of progression) or approximately up to 2.5 years.

Secondary Outcomes (9)

• Overall survival (OS)

  To assess every 8 weeks (±7 days) for first 72 weeks following objective disease progression or treatment discontinuation and then every 12 weeks, up to approximately 2.5 years.

• Time to second progression

  To assess every 8 weeks (±7 days) for first 72 weeks following objective disease progression or treatment discontinuation and then every 12 weeks, up to approximately 2.5 years.

• Objective response rate

  At baseline, every 8 weeks for first 72 weeks, then every 12 weeks after randomization until objective disease progression or approximately up to 2.5 years.

• Duration of response

  At baseline, every 8 weeks for first 72 weeks, then every 12 weeks after randomization until objective disease progression or approximately up to 2.5 years.

• Percentage change in tumour size

  At baseline, every 8 weeks for first 72 weeks, then every 12 weeks after randomization until objective disease progression or approximately up to 2.5 years.

Other Outcomes (35)

• Number of participants with adverse events (AEs)

  From Cycle 1 Day 1 to follow-up 30 days after the last dose of study medication.

• Number of participants with abnormal physical examination

  From Cycle 1 Day 1 to follow-up 30 days after the last dose of study medication.

• Number of participants with abnormal Eastern Cooperative Oncology Group (ECOG) performance status (PS)

  From Cycle 1 Day 1 to follow-up 30 days after the last dose of study medication.

Study Arms (3)

Arm 1 (ceralasertib+olaparib)

EXPERIMENTAL

Participants received ceralasertib 160 mg QD PO on Days 1 to 7 plus olaparib 300 mg BD PO continuous (28 day cycle).

Drug: Olaparib; Drug: Ceralasertib

Arm 2 (olaparib monotherapy)

EXPERIMENTAL

Olaparib 300 mg BD PO daily continuous.

Drug: Olaparib

Arm 3 (placebo)

EXPERIMENTAL

Placebo to match olaparib BD PO daily continuous.

Drug: Placebo to match olaparib

Interventions

Olaparib DRUG

Olaparib 300 mg BD (2 × 150 mg tablets) continually in the olaparib monotherapy and ceralasertib+olaparib treatment arms.

Also known as: AZD2281

Arm 1 (ceralasertib+olaparib); Arm 2 (olaparib monotherapy)

Ceralasertib DRUG

Ceralasertib 160 mg QD (2 × 80 mg tablets) from Days 1 to 7 (inclusive) of every 28-day cycle.

Also known as: AZD6738

Arm 1 (ceralasertib+olaparib)

Placebo to match olaparib DRUG

Per olaparib

Arm 3 (placebo)

Eligibility Criteria

• Age: 18 Years - 130 Years
• Gender Eligibility Details: Female ≥18 years of age at the time of signing the informed consent form (ICF).
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of providing signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the Clinical Study Protocol (CSP).
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Female ≥18 years of age at the time of signing the ICF.
• Eastern Cooperative Oncology Group performance status 0 to 1 within 28 days of randomization.
• Participants with relapsed histologically confirmed diagnosis of high grade epithelial ovarian cancer (including primary peritoneal and/or fallopian tube cancer), with disease relapse on or after completion of PARPi maintenance therapy and who have not received any intervening systemic treatment since discontinuation of PARPi (this excludes the platinum based chemotherapy received during Screening Part 1 of this study).
• A minimum of 6 months of prior PARPi treatment received in the maintenance setting for PSR ovarian cancer (a minimum of 12 months is required if the participant received PARPi maintenance following first line chemotherapy). If the prior PARPi used was olaparib then participants must have received treatment without significant toxicity or the need for a permanent dose reduction.
• Disease relapse in the second line (first relapse) or third line (second relapse) setting.
• Able to provide and consent to the collection of a contemporaneous tumor tissue biopsy and blood sample.
• Able to provide a Formalin Fixed Paraffin Embedded archival tumour tissue block from the time of primary tumour diagnosis (taken ideally prior to receiving any systemic treatment, and definitely prior to first PARPi treatment) for prospective Breast cancer susceptibility gene (BRCA) status testing. If tumour blocks are unavailable, tissue sections are acceptable with a minimum requirement of at least 20 unstained sections on uncharged slides without cover slips. Fine needle aspirates are not acceptable.
• Where the patient has previously been tested for germline or somatic BRCA alterations using a verified and well-validated test in line with local regulations, performed in a locally accredited laboratory (eg, College of American Pathologists/Clinical Laboratory Improvement Amendments laboratory, where available), and signed consent to provide a copy of the BRCA report.
• Platinum-sensitive disease at the time of disease relapse, i.e, platinum-treatment free survival of greater than 6 months as defined by the Gynecological Cancer Intergroup (Wilson et al 2017).
• For the platinum-based chemotherapy course received following pre screening (Part 1) and prior to entering the main screening (Part 2).
• Any prior palliative radiation must have been completed at least 7 days prior to the start of study drugs, and participants must have recovered from any acute adverse effects prior to the start of study treatment.
• Normal organ and bone marrow function measured within 28 days prior to randomization.
• Participant is willing and able to comply with the CSP for the duration of the study including undergoing treatment and scheduled visits and examinations.

You may not qualify if:

• Participants who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen or during the period between completion of chemotherapy and first dose of study treatment.
• Participants with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
• History of leptomeningeal carcinomatosis.
• Participants with symptomatic uncontrolled brain metastases.
• A scan to confirm the absence of brain metastases is not required.
• Participants whose brain metastases have been treated may participate provided they show radiographic stability. In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade \<2) either, without the use of steroids, or are stable on a steroid dose of ≤10 mg/day of prednisone or its equivalent and stable on anti convulsants if required for at least 14 days prior to the start of treatment.
• Participants with spinal cord compression are not eligible unless considered to have received definitive treatment for this and have evidence of clinically SD for \>28 days and have not received steroid treatment for at least 14 days prior to the start of study treatment.
• 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 IP and of low potential risk for recurrence;
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
• Adequately treated carcinoma in situ without evidence of disease.
• Major surgical procedures (as defined by the investigator) ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days. No waiting period required following port a cath or other central venous access placement.
• Persistent toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy. Note: participants with signs of ongoing complications from radiation therapy are not eligible for this study.
• Participants with myelodysplastic syndrome (MDS) /acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
• Resting electrocardiogram indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator, or participants with congenital long QT syndrome.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (26)

Research Site

Anchorage, Alaska, 99508, United States

Location

Research Site

La Jolla, California, 92093-0021, United States

Location

Research Site

Long Beach, California, 90806, United States

Location

Research Site

Los Angeles, California, 90048, United States

Location

Research Site

West Hollywood, California, 97210, United States

Location

Research Site

Hartford, Connecticut, 06106, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Atlanta, Georgia, 30342, United States

Location

Research Site

Louisville, Kentucky, 40202, United States

Location

Research Site

Covington, Louisiana, 70433, United States

Location

Research Site

Florham Park, New Jersey, 07932, United States

Location

Research Site

Teaneck, New Jersey, 07666, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Tulsa, Oklahoma, 74146, United States

Location

Research Site

Portland, Oregon, 97210, United States

Location

Research Site

Abington, Pennsylvania, 19001, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Sioux Falls, South Dakota, 57105-1599, United States

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Research Site

Sioux Falls, South Dakota, 57105, United States

Location

Research Site

Houston, Texas, 77030, United States

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Research Site

Seattle, Washington, 98104, United States

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Montreal, Quebec, H3A 1A1, Canada

Location

Research Site

Napoli, 80131, Italy

Location

Research Site

Barcelona, 8035, Spain

Location

Related Publications (1)

• McMullen M, Karakasis K, Loembe B, Dean E, Parr G, Oza AM. DUETTE: a phase II randomized, multicenter study to investigate the efficacy and tolerability of a second maintenance treatment in patients with platinum-sensitive relapsed epithelial ovarian cancer, who have previously received poly(ADP-ribose) polymerase (PARP) inhibitor maintenance treatment. Int J Gynecol Cancer. 2020 Nov;30(11):1824-1828. doi: 10.1136/ijgc-2020-001694. Epub 2020 Sep 2.

  PMID: 32878963 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib; ceralasertib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Dr Amit Oza, MD (Lon) FRCP FRCPC

  Princess Margaret Cancer Centre, UHN and Mt. Sinai Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The olaparib and placebo arms will be double blinded, whereas the ceralasertib+olaparib arm will be open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: January 23, 2020
• Study Start: August 7, 2020
• Primary Completion: January 25, 2021
• Study Completion: January 25, 2021
• Last Updated: March 10, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please re-refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (22); IT (1); CA (2); ES (1)