Back to resultsDelayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
Primary Purpose
Ovarian Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Olaparib
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring PARP-I, BRCA mutation, Epithelial ovarian cancer (EOC), Olaparib, platinum sensitive, recurrent ovarian carcinoma, Poly ADP-Ribose Polymerase (PARP) inhibitor.
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
Sites / Locations
- Magee Women's Hospital of UPMC
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Olaparib
Arm Description
Olaparib dosed at 300mg orally twice daily, started when CA125 rises by two-fold of nadir value.
Outcomes
Primary Outcome Measures
Time to Next Therapy
The time to next therapy from completion of platinum-based therapy for treatment of recurrence until initiation of post-olaparib treatment.
Secondary Outcome Measures
Progression-free Survival (PFS)
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)
Overall survival as defined as the time from enrollment to death from any cause.
Adverse Events Possibly, Probably or Definitely Related to Treatment
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)
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)
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
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)
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)
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).
Full Information
NCT ID
NCT04377087
First Posted
May 1, 2020
Last Updated
June 13, 2023
Sponsor
Sarah E Taylor
Collaborators
American Society of Clinical Oncology
1. Study Identification
Unique Protocol Identification Number
NCT04377087
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Slow enrollment
Study Start Date
June 29, 2020 (Actual)
Primary Completion Date
May 31, 2023 (Actual)
Study Completion Date
May 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Sarah E Taylor
Collaborators
American Society of Clinical Oncology
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
PARP-I, BRCA mutation, Epithelial ovarian cancer (EOC), Olaparib, platinum sensitive, recurrent ovarian carcinoma, Poly ADP-Ribose Polymerase (PARP) inhibitor.
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Olaparib
Arm Type
Experimental
Arm Description
Olaparib dosed at 300mg orally twice daily, started when CA125 rises by two-fold of nadir value.
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
Lynparza™
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to Next Therapy
Description
The time to next therapy from completion of platinum-based therapy for treatment of recurrence until initiation of post-olaparib treatment.
Time Frame
Up to 42 months
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
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).
Time Frame
Up to 42 months
Title
Overall Survival (OS)
Description
Overall survival as defined as the time from enrollment to death from any cause.
Time Frame
Up to 42 months
Title
Adverse Events Possibly, Probably or Definitely Related to Treatment
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.
Time Frame
Up to 30 days after discontinuation of treatment (for individual patient)
Title
Overall Response Rate (ORR)
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.
Time Frame
Up to 42 months
Title
The Functional Assessment of Cancer Therapy + Ovarian-specific scale (FACT-O)
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).
Time Frame
Up to 42 months
Title
PROMIS Physical Function-20a
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).
Time Frame
Up to 42 months
Title
Assessment of Survivor Concerns (ASC) Worry Subscale and Impact of Event Scale (IES-R)
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.
Time Frame
Up to 42 months
Title
Modified Collection of Indirect and Non-medical Direct Costs (COIN)
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).
Time Frame
Up to 42 months
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Gynecological cancers
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarah Taylor, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Magee Women's Hospital of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer
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