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.
- Pancreatic Adenocarcinoma
- Brief Title: Olaparib for BRCAness Phenotype in Pancreatic Cancer
- Official Title: Olaparib for BRCAness Phenotype in Pancreatic Cancer: Phase II Study
Clinical Trial IDs
- ORG STUDY ID:
- SECONDARY ID:
- NCT ID:
The goal of this clinical research study is to learn if olaparib can help to control
metastatic pancreatic cancer. The safety of this drug will also be studied.
This is an investigational study. Olaparib is FDA approved and commercially available for the
treatment of ovarian cancer. Its use in this study is investigational. The study doctor can
explain how the study drug is designed to work.
Up to 34 participants will be enrolled in this study. All will take part at MD Anderson.
|Olaparib||Experimental||Participants receive Olaparib tablets in a dose of 300 mg orally (p.o.) twice daily. Treatment continues until progression, intolerable toxicity or as per participant's preference. Each treatment cycle is 28 days long.|
1. Patients with histologically or cytologically confirmed metastatic adenocarcinoma of
2. 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 HRD will be eligible even in the absence of family history [e.g. somatic BRCA
mutation, Fanconi Anemia gene, ATM or RAD51 mutations].
3. 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
4. Patients must have received at least one prior therapy for metastatic disease to be
5. 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 CT scan.
6. All treated patients have the option to undergo pre-treatment biopsy (liver, omentum,
lung or lymph node) to be eligible.
7. Patients with prior malignancy and treated with no evidence of active disease, and
more than 2 years from initial diagnosis are eligible.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (Karnofsky >70).
9. Patients must have adequate organ and marrow function as defined below: 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);
AST(SGOT)/ALT(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
10. International Normalized Ratio (INR) < 1.5.
11. Patients must be >/= 18 years of age.
12. 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.
13. 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
1. Uncontrolled intercurrent illness including symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI) within 3
months of initiation of therapy.
2. Patients whose tumors are deemed to be platinum-refractory will be excluded from the
3. Pregnancy or lactation.
4. Patient has active and uncontrolled bacterial, viral, or fungal infection(s) requiring
5. Patient has undergone major surgical resection within 4 weeks prior to enrollment.
6. Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy
within 2 weeks prior to study entry.
7. 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
8. Serious psychiatric or medical conditions that could interfere with treatment.
9. Major bleeding in the last 4 weeks prior to study entry.
10. Concomitant use of CYP3A4 inhibitors.
11. Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470msec.
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|
Primary Outcome Measures
|Measure:||Objective Tumor Response Rate of Olaparib in Participants with Pancreatic Cancer|
|Time Frame:||8 weeks|
|Description:||Objective tumor response assessment based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria of response: complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD), no evidence of disease (NED) and not evaluable (NE).|
Secondary Outcome Measures
|Measure:||Efficacy of Olaparib in Participants with Pancreatic Cancer|
|Time Frame:||8 weeks|
|Description:||Efficacy assessed by objective tumor assessments until objective radiological disease progression as defined by RECIST.|
|Lead Sponsor:||M.D. Anderson Cancer Center|
- Pancreatic Cancer
- Stage IV pancreatic ductal adenocarcinoma (PDAC) with BRCAness
- Metastatic adenocarcinoma of the pancreas
- Family history of breast cancer
- Family history of ovarian cancer
- Family history of pancreatic cancer
- Family history of gastric cancer
- Family history of prostate cancer