Olaparib in Treating Patients With Stage IV Pancreatic Cancer

Phase 2

Completed

Conditions: Pancreatic Ductal Adenocarcinoma
Stage IV Pancreatic Cancer AJCC v6 and v7
Metastatic Pancreatic Adenocarcinoma

Interventions: Drug: Olaparib

Registration Number: NCT02677038

Lead Sponsor: M.D. Anderson Cancer Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (olaparib)	Olaparib	Patients receive olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	5 years 8 months	The primary endpoint was the objective response rate assessed by the investigator using the modified RECIST v1.1 criteria.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	5 years 8 months	The Progression Free Survival defined as the time from enrollment until radiologic disease progression and it is assessed by the investigator review using modified RECIST v1.1 criteria or by death by any cause. This was applied to all patients from MD Anderson Cancer Center Houston Tx USA.
Overall Survival	5 years 8 months	Overall Survival is defined as the time from the date of enrollment to the date of death or last follow up. This was applied to all patients from MD Anderson Cancer Center Houston Tx USA