Olaparib in Treating Patients With Stage IV Pancreatic Cancer
Primary Purpose
Metastatic Pancreatic Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, Stage IV Pancreatic Cancer AJCC v6 and v7
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Olaparib
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
- Patients with histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas
- Family history: one or more close blood relative with ovarian carcinoma at any age or breast cancer age 50 or younger or two relatives with breast, pancreatic or prostate cancer (Gleason 7 or higher) at any age, or patients with Ashkenazi Jewish ancestry; however, patients with previously identified genetic aberrations that are associated with homologous recombination deficiency (HRD) will be eligible even in the absence of family history (e.g. somatic BRCA mutation, Fanconi anemia gene, ATM or RAD51 mutations)
- Patients must be germline BRCA 1 or 2 negative; (Note: if BRCA status was previously determined, that result is acceptable but documentation of status must be available; subjects with unknown status will be referred to genetic counselling for BRCA testing as per standard of care) and/or patients with previously identified genetic aberrations that are associated with HRD will be eligible even in the absence of family history (e.g. somatic BRCA mutation, Fanconi Anemia gene, ATM or RAD51 mutations)
- Patients must have received at least one prior therapy for metastatic disease to be eligible
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
- All treated patients have the option to undergo pre-treatment biopsy (liver, omentum, lung or lymph node) to be eligible
- Patients with prior malignancy and treated with no evidence of active disease, and more than 2 years from initial diagnosis are eligible
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky > 70)
- Leukocytes >= 3,000 cells/mm^3
- Absolute neutrophil count >= 1,500 cells/mm^3
- Platelets >= 75,000 cells/mm^3
- Hemoglobin >= 9 g/dl (no blood transfusions within 4 weeks prior to enrollment)
- Total bilirubin < 1.5 x institutional upper limit of normal (IULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x IULN without liver metastasis; =< 5 x IULN for patients with liver metastasis
- Creatinine not greater than upper institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- International normalized ratio (INR) < 1.5
- Women of childbearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use two highly effective forms of contraception while they are receiving study treatment and for 30 days after last dose of study drug; male subjects must agree to refrain from sperm donation during the study and for 30 days after the last dose of study drugs
- Ability to understand and the willingness to sign a written informed consent document; signed informed consent form must be obtained prior to initiation of study evaluations and/or activities
Exclusion Criteria:
- Uncontrolled intercurrent illness including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI) within 3 months of initiation of therapy
- Patients whose tumors are deemed to be platinum-refractory will be excluded from the trial
- Pregnancy or lactation
- Patient has active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- Patient has undergone major surgical resection within 4 weeks prior to enrollment
- Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to study entry
- Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug
- Serious psychiatric or medical conditions that could interfere with treatment
- Major bleeding in the last 4 weeks prior to study entry
- Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
- Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec (Fridericia's scale)
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (olaparib)
Arm Description
Patients receive olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Objective response rate (defined as complete response or partial response) assessed using Response Evaluation Criteria in Solid Tumors 1.1
Simon's optimal two-stage design will be implemented for the study. The objective response rate and its corresponding exact 95% confidence interval will be estimated.
Secondary Outcome Measures
Overall survival (OS)
The Kaplan-Meier method will be used to estimate the probability of OS. The Log rank test and Cox proportional hazards models will be used to determine the association of OS with patient characteristics.
Progression free survival (PFS)
The Kaplan-Meier method will be used to estimate the probability of PFS. The Log rank test and Cox proportional hazards models will be used to determine the association of PFS with patient characteristics.
Change in cancer antigen 19-9 (CA19-9) clinical response
Defined as the percentage reduction before and after 8 weeks of treatment. The mean, standard deviation, median and range will be summarized for the percentage reduction of CA 19-9.
Incidence of unacceptable toxicity
Defined as treatment related grade 3 or higher toxicities graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Unacceptable toxicities will be monitored closely using the method of Thall et al.
Full Information
NCT ID
NCT02677038
First Posted
February 4, 2016
Last Updated
July 5, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT02677038
Brief Title
Olaparib in Treating Patients With Stage IV Pancreatic Cancer
Official Title
Olaparib for BRCAness Phenotype in Pancreatic Cancer: Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
November 11, 2016 (Actual)
Primary Completion Date
July 18, 2022 (Actual)
Study Completion Date
July 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase II trial studies how well olaparib works in treating patients with stage IV pancreatic cancer. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the efficacy of olaparib monotherapy in stage IV pancreatic ductal adenocarcinoma (PDAC) with breast cancer, early onset (BRCA)ness.
SECONDARY OBJECTIVES:
I. To further determine the efficacy of olaparib in the study population.
SAFETY OBJECTIVES:
I. To assess the safety and tolerability of olaparib.
EXPLORATORY OBJECTIVES:
I. To identify tissue based biomarkers of defective homologous recombination repair (HRD).
OUTLINE:
Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 8 weeks thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, Stage IV Pancreatic Cancer AJCC v6 and v7
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (olaparib)
Arm Type
Experimental
Arm Description
Patients receive olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Objective response rate (defined as complete response or partial response) assessed using Response Evaluation Criteria in Solid Tumors 1.1
Description
Simon's optimal two-stage design will be implemented for the study. The objective response rate and its corresponding exact 95% confidence interval will be estimated.
Time Frame
At 24 weeks
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
The Kaplan-Meier method will be used to estimate the probability of OS. The Log rank test and Cox proportional hazards models will be used to determine the association of OS with patient characteristics.
Time Frame
Time from date of study entry to the date of death from any cause or to the date of last follow-up if patients are alive, assessed up to 3 years
Title
Progression free survival (PFS)
Description
The Kaplan-Meier method will be used to estimate the probability of PFS. The Log rank test and Cox proportional hazards models will be used to determine the association of PFS with patient characteristics.
Time Frame
Time from the date of study entry to the date of progression or to the date of death from any cause, whichever occurred first, or to the last follow-up date if patients are alive without disease progression, assessed up to 3 years
Title
Change in cancer antigen 19-9 (CA19-9) clinical response
Description
Defined as the percentage reduction before and after 8 weeks of treatment. The mean, standard deviation, median and range will be summarized for the percentage reduction of CA 19-9.
Time Frame
Baseline to up to 8 weeks
Title
Incidence of unacceptable toxicity
Description
Defined as treatment related grade 3 or higher toxicities graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Unacceptable toxicities will be monitored closely using the method of Thall et al.
Time Frame
Up to 30 days after the completion of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas
Family history: one or more close blood relative with ovarian carcinoma at any age or breast cancer age 50 or younger or two relatives with breast, pancreatic or prostate cancer (Gleason 7 or higher) at any age, or patients with Ashkenazi Jewish ancestry; however, patients with previously identified genetic aberrations that are associated with homologous recombination deficiency (HRD) will be eligible even in the absence of family history (e.g. somatic BRCA mutation, Fanconi anemia gene, ATM or RAD51 mutations)
Patients must be germline BRCA 1 or 2 negative; (Note: if BRCA status was previously determined, that result is acceptable but documentation of status must be available; subjects with unknown status will be referred to genetic counselling for BRCA testing as per standard of care) and/or patients with previously identified genetic aberrations that are associated with HRD will be eligible even in the absence of family history (e.g. somatic BRCA mutation, Fanconi Anemia gene, ATM or RAD51 mutations)
Patients must have received at least one prior therapy for metastatic disease to be eligible
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
All treated patients have the option to undergo pre-treatment biopsy (liver, omentum, lung or lymph node) to be eligible
Patients with prior malignancy and treated with no evidence of active disease, and more than 2 years from initial diagnosis are eligible
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky > 70)
Leukocytes >= 3,000 cells/mm^3
Absolute neutrophil count >= 1,500 cells/mm^3
Platelets >= 75,000 cells/mm^3
Hemoglobin >= 9 g/dl (no blood transfusions within 4 weeks prior to enrollment)
Total bilirubin < 1.5 x institutional upper limit of normal (IULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x IULN without liver metastasis; =< 5 x IULN for patients with liver metastasis
Creatinine not greater than upper institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
International normalized ratio (INR) < 1.5
Women of childbearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use two highly effective forms of contraception while they are receiving study treatment and for 30 days after last dose of study drug; male subjects must agree to refrain from sperm donation during the study and for 30 days after the last dose of study drugs
Ability to understand and the willingness to sign a written informed consent document; signed informed consent form must be obtained prior to initiation of study evaluations and/or activities
Exclusion Criteria:
Uncontrolled intercurrent illness including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI) within 3 months of initiation of therapy
Patients whose tumors are deemed to be platinum-refractory will be excluded from the trial
Pregnancy or lactation
Patient has active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
Patient has undergone major surgical resection within 4 weeks prior to enrollment
Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to study entry
Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug
Serious psychiatric or medical conditions that could interfere with treatment
Major bleeding in the last 4 weeks prior to study entry
Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec (Fridericia's scale)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Milind Javle
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website
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Olaparib in Treating Patients With Stage IV Pancreatic Cancer
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