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Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive olaparib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans or CT/MRI and collection of blood throughout the study.

Patients receive placebo PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans or CT/MRI and collection of blood throughout the study.

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Nicholas DiBella

John A. Ellerton

Stephen W. Behrman

Ari D. Baron

Timothy E. Byun

Brian G. Vikstrom

Michael J. Pishvaian

Mohamedtaki A. Tejani

Nkiruka Ezenwajiaku

Shishir K. Maithel

Alison K. Conlin

Bryan A. Faller

Shikha Jain

Ardaman Shergill

Suparna Mantha

Hollis Walker

Kim A Reiss Binder

This phase II trial investigates how well the addition of olaparib following completion of surgery and chemotherapy works in treating patients with pancreatic cancer that has been surgically removed (resected) and has a pathogenic mutation in BRCA1, BRCA2, or PALB2. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.

PRIMARY OBJECTIVE:

I. To determine the relapse-free survival (RFS)-benefit from the addition of a maintenance olaparib following completion of chemotherapy in patients with resected pancreatic carcinoma and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2.

SECONDARY OBJECTIVES:

I. To evaluate RFS in patients with olaparib after perioperative chemotherapy compared to those treated with perioperative therapy alone among patients who received prior platinum-based perioperative chemotherapy.

II. To evaluate overall survival (OS) in patients treated with olaparib after adjuvant chemotherapy compared to those treated with adjuvant treatment alone.

III. To analyze the efficacy of olaparib after chemotherapy in patients with a pathogenic germline BRCA or PALB2 mutation compared to those with a somatic mutation.

IV. To analyze survival differences between patients who received neoadjuvant or perioperative chemotherapy compared to those who received adjuvant therapy alone.

V. To analyze RFS and OS differences in those who received =\< 3 months of perioperative platinum chemotherapy compared to those who received \> 3 months of perioperative platinum chemotherapy.

VI. To analyze RFS and OS differences in those who received any platinum-based perioperative chemotherapy compared to no-platinum based perioperative chemotherapy.

EXPLORATORY OBJECTIVES:

I. To analyze RFS and OS differences in patients who had R1 versus (vs) R0 resections, lymph node positivity at resection, and/or elevated or rising CA 19-9 or CEA at time of study enrollment in the post-operative setting.

II. To analyze RFS and OS differences with those who had resectable disease at diagnosis compared to those who did not.

III. To analyze RFS and OS differences in those with gBRCA1 mutations compared to those with gBRCA2 mutations and gPALB2 mutations.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scans or CT/magnetic resonance imaging (MRI) and collection of blood throughout the study.

ARM II: Patients receive placebo PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans or CT/MRI and collection of blood throughout the study.

After completion of study treatment, patients are followed up at 30 days, every 4 months for year 1, then every 6 months for years 2-10 after randomization.

APOLLO: A Randomized Phase II Double-Blind Study of Olaparib Versus Placebo Following Curative Intent Therapy in Patients With Resected Pancreatic Cancer and a Pathogenic BRCA1, BRCA2 or PALB2 Mutation

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A cutoff of 35 will be used to determine elevated versus normal CA 19-9 (i.e., greater than 35 will be considered elevated), and the cutoff for CEA will be based on the treating institution's definition of the upper limit of normal. Univariate differences by marker status will be analyzed and Cox proportional hazards models will be fit, adjusting for other clinical and demographic factors that may be confounders.

Will demonstrate an improvement in the RFS from 22 months to 44 months (hazard ratio 0.5) in patients treated with olaparib after perioperative (neoadjuvant, adjuvant or a combination) chemotherapy compared to those treated with perioperative therapy alone.

Will evaluate RFS in patients with olaparib after perioperative chemotherapy compared to those treated with perioperative therapy alone. Analysis will be largely exploratory. Within each arm any proportion endpoint (toxicity, mutation rate, etc.) will be estimable with a 95% confidence interval. Arm A would have a confidence interval that is 20 percentage points wide, and Arm B would have a confidence interval that is 29 percentage points wide.

Analysis will be largely exploratory. Power for overall survival in particular will be limited. Within each arm any proportion endpoint (toxicity, mutation rate, etc.) will be estimable with a 95% confidence interval. Arm A would have a confidence interval that is 20 percentage points wide, and Arm B would have a confidence interval that is 29 percentage points wide.

Will analyze the efficacy of olaparib after chemotherapy in patients with a pathogenic germline BRCA or PALB2 mutation compared to those with a somatic mutation.

Will analyze survival differences between patients who received neoadjuvant or perioperative chemotherapy compared to those who received adjuvant therapy alone.

Analysis will be largely exploratory. Within each arm any proportion endpoint (toxicity, mutation rate, etc.) will be estimable with a 95% confidence interval. Arm A would have a confidence interval that is 20 percentage points wide, and Arm B would have a confidence interval that is 29 percentage points wide.

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
APOLLO: A Randomized Phase II Double-Blind Study of Olaparib Versus Placebo Following Curative Intent Therapy in Patients With Resected Pancreatic Cancer and a Pathogenic BRCA1, BRCA2 or PALB2 Mutation	NCT04858334	Pancreatic Acin... Pancreatic Aden... Pancreatic Squa... Resectable Panc... Resectable Panc... Resectable Panc... Resectable Panc...	Biospecimen Col... Computed Tomogr... Magnetic Resona... Olaparib Placebo Adminis...	18 Years -	National Cancer Institute (NCI)
APOLLO: A Randomized Phase II Double-Blind Study of Olaparib Versus Placebo Following Curative Intent Therapy in Patients With Resected Pancreatic Cancer and a Pathogenic BRCA1, BRCA2 or PALB2 Mutation	NCT04858334	Pancreatic Acin... Pancreatic Aden... Pancreatic Squa... Resectable Panc... Resectable Panc... Resectable Panc... Resectable Panc...	Biospecimen Col... Computed Tomogr... Magnetic Resona... Olaparib Placebo Adminis...	18 Years -	National Cancer Institute (NCI)

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