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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. Identifier: NCT04377087
Recruitment Status : Recruiting
First Posted : May 6, 2020
Last Update Posted : August 7, 2020
American Society of Clinical Oncology
Information provided by (Responsible Party):
Sarah E Taylor, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE May 1, 2020
First Posted Date  ICMJE May 6, 2020
Last Update Posted Date August 7, 2020
Actual Study Start Date  ICMJE June 29, 2020
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2020)
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
Official Title  ICMJE Phase IIA Trial of Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE Drug: 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.
Other Name: Lynparza™
Study Arms  ICMJE Experimental: Olaparib
Olaparib dosed at 300mg orally twice daily, started when CA125 rises by two-fold of nadir value.
Intervention: Drug: Olaparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 1, 2020)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Gynecological cancers
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Brenda L Steele, BSN 412-641-3418 steebx@UPMC.EDU
Contact: Donna Haney 412-389-5208
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04377087
Other Study ID Numbers  ICMJE HCC 19-164
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sarah E Taylor, University of Pittsburgh
Study Sponsor  ICMJE Sarah E Taylor
Collaborators  ICMJE American Society of Clinical Oncology
Investigators  ICMJE
Principal Investigator: Sarah Taylor, MD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP