Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer

NCT ID: NCT04377087

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-29
• Study Completion Date: 2023-05-31

Brief Summary

The purpose of this study is to test if delaying the start of the olaparib until there is a rise in a tumor marker called CA-125 will result in a longer time until the next or different treatment for the patient's cancer. The study will also evaluate how delaying the start of maintenance therapy will affect symptoms; physical functioning; quality of life; and impact on finances.

Detailed Description

This is a Phase II trial will investigate if waiting until the time of chemical recurrence, denoted by rising CA125, to start a PARP inhibitor will lead to an improved time to next therapy with improved quality of life and at a lower financial toxicity.

PARP-I have shown efficacy as both monotherapy and as maintenance therapy. This trial will explore whether patients with recurrent ovarian cancer could derive the same efficacy benefit from a delayed start of a PARP-I compared to immediate maintenance therapy. Delayed start would have the benefit of sparing the physical, psychological, and financial toxicity associated with prolonged treatment. This approach would be particularly relevant in a population of platinum-sensitive patients who can have prolonged treatment-free intervals.

With widespread use of PARP-I, regardless of timing, understanding, and overcoming PARP-I resistance is becoming a major clinical need.

Enrollment will start within 8 weeks of completion of platinum-based treatment. Monitored with CA 125 levels every 28 days. Olaparib will be started when CA 125 rises by two-fold of their nadir value. Olaparib will be dosed at 300 mg orally twice a day, 28 days of treatment will be a cycle. Follow-up will consist of CA125 drawn every 28 days and CT scans obtained at doubling of CA- 125 and then every 12 weeks* to assess for recurrence or progression. Clinician- and patient-reported adverse events recorded every 28 days. Cancer-related worry and distress assessed every 28 days. Measures of quality of life and physical function, and financial toxicity assessed every 12 weeks.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olaparib

Olaparib dosed at 300mg orally twice daily, started when CA125 rises by two-fold of nadir value.

Group Type: EXPERIMENTAL

Olaparib

Intervention Type: DRUG

Olaparib is a potent oral poly (ADP-ribose) polymerase (PARP) inhibitor that induces synthetic lethality in BRCA1/2 deficient tumor cells through the formation of double-stranded DNA breaks which cannot be accurately repaired, which leads to disruption of cellular homeostasis and cell death.

Interventions

Olaparib

Olaparib is a potent oral poly (ADP-ribose) polymerase (PARP) inhibitor that induces synthetic lethality in BRCA1/2 deficient tumor cells through the formation of double-stranded DNA breaks which cannot be accurately repaired, which leads to disruption of cellular homeostasis and cell death.

Intervention Type: DRUG

Other Intervention Names

Lynparza™

Eligibility Criteria

Inclusion Criteria

• Patient has platinum-sensitive, recurrent ovarian, fallopian-tube or peritoneal cancer. Platinum sensitivity is defined as complete clinical remission after frontline chemotherapy lasting greater than 6 months
• Patient has completed at least 2 courses of platinum-based chemotherapy with a PR or CR as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.139 or a CA-125 response, according to Gynecological Cancer InterGroup (GCIG) criteria40
• BRCA testing required (results not needed for registration)
• ECOG performance status score of 0, 1, or 2 (See Appendix A)
• Life expectancy greater than 6 months
• Normal organ and marrow function as defined: 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); Serum creatinine ≤ 1.5 mg/dL; Total serum bilirubin ≤ 1.5 x ULN; AST and ALT ≤ 2.5 x ULN
• Able to take oral medication
• Not pregnant and not breastfeeding
• Able to understand and willingness to sign a written informed consent document
• Patients must be enrolled within 8 weeks of completing last cycle of chemotherapy

Exclusion Criteria

• Patient has had a prior invasive malignancy diagnosed within the last five years (except [1] non-melanoma skin cancer or [2] prior in situ carcinoma of the cervix or breast [3] has been without evidence of invasive disease for greater than 3 years)
• Patients receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib
• Uncontrolled intercurrent illness that could affect their participation in the study including, but not limited to, ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; known inadequately controlled hypertension; significant pulmonary disease including dyspnea at rest, patients requiring supplemental oxygen, or poor pulmonary reserve; or psychiatric illness/social situations that would limit compliance with study requirements
• Impairment of gastrointestinal function or disease that may significantly alter the absorption of olaparib
• Patients who have received prior treatment with a PARP inhibitor
• History of noncompliance to medical regimens

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

American Society of Clinical Oncology

OTHER

Sponsor Role: collaborator

Sarah E Taylor

OTHER

Sponsor Role: lead

Responsible Party

Sarah E Taylor

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sarah Taylor, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Magee Women's Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HCC 19-164

Identifier Type: -

Identifier Source: org_study_id