Clinical Trials /

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

NCT04377087

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: HCC 19-164
  • NCT ID: NCT04377087

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
OlaparibLynparzaOlaparib

Purpose

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.
    

Trial Arms

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

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to Next Therapy
Time Frame:Up to 42 months
Safety Issue:
Description:The time to next therapy from completion of platinum-based therapy for treatment of recurrence until initiation of post-olaparib treatment.

Secondary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Up to 42 months
Safety Issue:
Description: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).
Measure:Overall Survival (OS)
Time Frame:Up to 42 months
Safety Issue:
Description:Overall survival as defined as the time from enrollment to death from any cause.
Measure:Adverse Events Possibly, Probably or Definitely Related to Treatment
Time Frame:Up to 30 days after discontinuation of treatment (for individual patient)
Safety Issue:
Description: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.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 42 months
Safety Issue:
Description: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.
Measure:The Functional Assessment of Cancer Therapy + Ovarian-specific scale (FACT-O)
Time Frame:Up to 42 months
Safety Issue:
Description: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).
Measure:PROMIS Physical Function-20a
Time Frame:Up to 42 months
Safety Issue:
Description: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).
Measure:Assessment of Survivor Concerns (ASC) Worry Subscale and Impact of Event Scale (IES-R)
Time Frame:Up to 42 months
Safety Issue:
Description: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.
Measure:Modified Collection of Indirect and Non-medical Direct Costs (COIN)
Time Frame:Up to 42 months
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sarah E Taylor

Trial Keywords

  • PARP-I
  • BRCA mutation
  • Epithelial ovarian cancer (EOC)
  • Olaparib
  • platinum sensitive
  • recurrent ovarian carcinoma
  • Poly ADP-Ribose Polymerase (PARP) inhibitor.

Last Updated

May 1, 2020