Upfront Maintenance Olaparib in Advanced Ovarian Cancer BRCAwt Patients With Known Homologous Recombination Deficiency

NCT06120972 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCC 22-066
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective non-randomized efficacy trial of olaparib maintenance therapy after frontline treatment with platinum-based therapy in advanced ovarian cancer patients with BRCAwt, homologous recombination deficient (HRD) disease.

Conditions

Ovarian Cancer

Keywords

BRCAwt; homologous recombination deficiency (HRD); PARP inhibitors; homologous recombination repair (HR)

Outcome Measures

Primary Outcomes (2)

• Time to progression (TTP)

  Time (median number of months) between enrolment and progression (defined by RECIST 1.1) or death, whichever occurs first, and censored at the last date of disease assessment in the absence of progressive disease. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  Up to 12 months

• 1-year Progression-free Survival (PFS)

  Percentage of participants free of disease progression at 1 year. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  Up to 12 months

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  Up to 6 years

• Second Progression-free Survival (PFS2)

  Up to 6 years

• Overall Survival (OS)

  Up to 6 years

• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)

  At Baseline, Every 12 weeks during treatment, at End of Treatment, Up to 3 years

Study Arms (1)

Olaparib (maintenance)

EXPERIMENTAL

300 mg Olaparib (tablets) will be taken orally, twice a day (approximately every twelve hours)

Drug: Olaparib tablet

Interventions

Olaparib tablet DRUG

Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase, an enzyme involved in DNA repair.

Also known as: Lynparza

Olaparib (maintenance)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance score of 0, 1, or 2
• Life expectancy ≥ 16 months
• Normal organ and marrow function as defined below: - Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L - Platelets ≥ 100 x 109 /L - Hemoglobin (Hgb) ≥ 8 g/dL (blood transfusions to reach this amount are allowed) Page 15 of 69 - Serum creatinine ≤ 1.5 mg/dL - Total serum bilirubin ≤ 1.5 x ULN -AST and ALT ≤ 2.5 x ULN
• Histologically confirmed advanced BRCAwt+ ovarian cancer with known recombinant deficiency
• Measurable disease per RECIST 1.1
• At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) or Clinical examination and, which is suitable for accurate repeated measurements. OR At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline using CT/MRI/plain x-ray and is suitable for repeated assessment.

You may not qualify if:

• Previous enrollment in the present study
• Participation in another clinical study with an investigational product (IP) in the last 3 months.
• BRCA 1 or 2 germline mutation
• Use of hyperthermic intraperitoneal chemotherapy as part of their upfront adjuvant therapy
• Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (ie germ cell tumors)
• Ovarian tumors of low malignant potential (eg borderline tumors) or mucinous carcinoma
• Synchronous primary endometrial cancer unless both of the following criteria are met:
• Stage \<II
• Aged \<60 years at the time of diagnosis of endometrial cancer with stage IA or IB grade I or II, or stage IA grade III endometrial carcinoma OR aged ≥60 years at the time of diagnosis of endometrial cancer with stage IA grade I or II endometrioid adenocarcinoma. Subjects with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible
• Other malignancy within the last 5 years except adequately treated non-melanoma skin cancer; curatively treated in situ cancer of the cervix; ductal carcinoma in situ. Subjects with a history of localized malignancy diagnosed over 5 years ago may be eligible provided they completed adjuvant systemic therapy prior to enrollment and remain free of recurrent or metastatic disease.
• Subjects with a history of primary triple-negative breast cancer may be eligible provided they completed definitive anticancer treatment more than 3 years ago and remain breast cancer free prior to start of study treatment
• Subjects with MDS/ AML history
• Subjects who experienced, for at least one cycle, a delay of \>2 weeks because of prolonged hematologic recovery during first-line chemotherapy
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment Major surgery within 4 weeks of starting study treatment; subjects must have recovered from any effects of any major surgery
• Previous allogenic bone marrow transplantation or double umbilical cord blood transplantation (dUCBT).

Sponsors & Collaborators

• Alexander B Olawaiye, MD: lead
• AstraZeneca: collaborator

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib

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

• Alexander B Olawaiye, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Obstetrics, Gynecology & Reproductive Sciences

Study Record Dates

• First Submitted: November 1, 2023
• First Posted: November 7, 2023
• Study Start: January 17, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share