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

Summary

Objectives

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.