Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04377087|
Recruitment Status : Recruiting
First Posted : May 6, 2020
Last Update Posted : August 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer||Drug: Olaparib||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase IIA Trial of Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer|
|Actual Study Start Date :||June 29, 2020|
|Estimated Primary Completion Date :||October 2023|
|Estimated Study Completion Date :||May 2024|
Olaparib dosed at 300mg orally twice daily, started when CA125 rises by two-fold of nadir value.
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.
Other Name: Lynparza™
- Time to Next Therapy [ Time Frame: Up to 42 months ]The time to next therapy from completion of platinum-based therapy for treatment of recurrence until initiation of post-olaparib treatment.
- Progression-free Survival (PFS) [ Time Frame: Up to 42 months ]Progression-free survival (PFS) defined as time from enrollment until detected recurrence or progression of disease, via Response Evaluation Criteria in Solid Tumors , or death from any cause.. Per RECIST 1.1, Progressive Disease (PD): At least a 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). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
- Overall Survival (OS) [ Time Frame: Up to 42 months ]Overall survival as defined as the time from enrollment to death from any cause.
- Adverse Events Possibly, Probably or Definitely Related to Treatment [ Time Frame: Up to 30 days after discontinuation of treatment (for individual patient) ]The rate of Serious Adverse Events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 that are possibly, probably or definitely related to study treatment.
- Overall Response Rate (ORR) [ Time Frame: Up to 42 months ]The proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- The Functional Assessment of Cancer Therapy + Ovarian-specific scale (FACT-O) [ Time Frame: Up to 42 months ]Health-related quality of life measured via The Functional Assessment of Cancer Therapy + Ovarian-specific scale (FACT-O). The FACT-O includes a list of statements that [other] people with ovarian cancer have said are important. The patient is asked to circle or mark one number per line to indicate their response as it applies to the prior 7 days. The scoring ranges from 0 (Not at all) to 4 (very much).
- PROMIS Physical Function-20a [ Time Frame: Up to 42 months ]Physical function assessed through the PROMIS Physical Function-20a assesses self-reported performance of physical activities. The PROMIS includes a list of statements related to physical performance, with scores of 0 (Always) to 5 (Rarely).
- Assessment of Survivor Concerns (ASC) Worry Subscale and Impact of Event Scale (IES-R) [ Time Frame: Up to 42 months ]The Assessment of Survivor Concerns (ASC) Worry Subscale and Impact of Event Scale (IES-R) will be used to measure worry and distress. The assessment includes a list of statements related to worry and stress experience during the patients prior, with responses ranging from 0 (Not at all) to 4 (Extremely). This assessment includes three subscales, the Intrusion subscale, the Avoidance subscale and the Hyperarousal subscale, which are each related to specific questions.
- Modified Collection of Indirect and Non-medical Direct Costs (COIN) [ Time Frame: Up to 42 months ]Financial toxicity measured through (a) monetary measure using the Modified Collection of Indirect and Non-medical Direct Costs (COIN), (b) objective measure of financial burden assessed using Barrera et al's Economic Hardship questionnaire, and (c) subjective measure of financial distress will be gauged using the Comprehensive Score for Financial Toxicity (COST Measure).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04377087
|Contact: Brenda L Steele, BSN||412-641-3418||steebx@UPMC.EDU|
|Contact: Donna Haneyfirstname.lastname@example.org|
|United States, Pennsylvania|
|Magee Women's Hospital of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Aja Yacobucci, RN 412-641-6372 email@example.com|
|Contact: Emily Staniszewski, RN 412-641-3578 firstname.lastname@example.org|
|Principal Investigator: Sarah Taylor, MD|
|Principal Investigator:||Sarah Taylor, MD||University of Pittsburgh|