Olaparib in Treating Patients With Stage IV Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT02677038|
Recruitment Status : Completed
First Posted : February 9, 2016
Last Update Posted : July 29, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Metastatic Pancreatic Adenocarcinoma Pancreatic Ductal Adenocarcinoma Stage IV Pancreatic Cancer AJCC v6 and v7||Drug: Olaparib||Phase 2|
I. To determine the efficacy of olaparib monotherapy in stage IV pancreatic ductal adenocarcinoma (PDAC) with breast cancer, early onset (BRCA)ness.
I. To further determine the efficacy of olaparib in the study population.
I. To assess the safety and tolerability of olaparib.
I. To identify tissue based biomarkers of defective homologous recombination repair (HRD).
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Olaparib for BRCAness Phenotype in Pancreatic Cancer: Phase II Study|
|Actual Study Start Date :||November 11, 2016|
|Actual Primary Completion Date :||July 18, 2022|
|Actual Study Completion Date :||July 18, 2022|
Experimental: Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Objective response rate (defined as complete response or partial response) assessed using Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: At 24 weeks ]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.
- Overall survival (OS) [ 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 ]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) [ 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 ]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 [ Time Frame: Baseline to up to 8 weeks ]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 [ Time Frame: Up to 30 days after the completion of study treatment ]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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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)
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): NCT02677038
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Milind Javle||M.D. Anderson Cancer Center|
|Responsible Party:||M.D. Anderson Cancer Center|
|Other Study ID Numbers:||
NCI-2016-00351 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0503 ( Other Identifier: M D Anderson Cancer Center )
|First Posted:||February 9, 2016 Key Record Dates|
|Last Update Posted:||July 29, 2022|
|Last Verified:||July 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Endocrine System Diseases
Poly(ADP-ribose) Polymerase Inhibitors
Molecular Mechanisms of Pharmacological Action