Clinical trial NCT04377087: Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
Official title: Phase IIA Trial of Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: PARP-I
BRCA mutation
Epithelial ovarian cancer (EOC)
Olaparib
platinum sensitive
recurrent ovarian carcinoma
Poly ADP-Ribose Polymerase (PARP) inhibitor.
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: American Society of Clinical Oncology
First posted: 2020-05-06
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to Next Therapy
timeFrame: Up to 35 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 35 months
measure: Overall Survival (OS)
timeFrame: Up to 35 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 35 months
measure: The Functional Assessment of Cancer Therapy + Ovarian-specific Scale (FACT-O)
timeFrame: Up to 37 months
measure: PROMIS Physical Function-20a
timeFrame: Up to 35 months
measure: Assessment of Survivor Concerns (ASC) Worry Subscale and Impact of Event Scale (IES-R)
timeFrame: Up to 35 months
measure: Modified Collection of Indirect and Non-medical Direct Costs (COIN)
timeFrame: Up to 35 months
measure: Adverse Events Possibly, Probably or Definitely Related to Treatment
timeFrame: Up to 35 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Magee Women's Hospital of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Sarah Taylor, MD
role: PRINCIPAL_INVESTIGATOR
References: