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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.

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Placebo Administration

Site Public Contact

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

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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)

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Patients receive nab-paclitaxel IV over 30-40 minutes, gemcitabine IV over 30-40 minutes, and cisplatin IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study.

Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study.

Nab paclitaxel

Jamie Crawley, MA

Shahzad Siddique

Donald S. Gravenor

Jennifer B. Valerin

Andrew H. Ko

John M. Schallenkamp

Joseph J. Merchant

Joshua Lukenbill

Deborah W. Wilbur

Richard L. Deming

Timothy Huyck

Rex B. Mowat

Vaibhav Sahai

Kathleen J. Yost

Daniel M. Anderson

This phase II/III trial compares the effect of the 3-drug chemotherapy combination of nab-paclitaxel, gemcitabine, plus cisplatin versus the 2-drug chemotherapy combination of nab-paclitaxel plus gemcitabine for the treatment of patients with pancreatic cancer that has spread to other places in the body (metastatic) and a known genetic mutation in the BRCA1, BRCA2, or PALB2 gene.

PRIMARY OBJECTIVES:

I. To evaluate and compare overall response rate (ORR) in patients with BRCA1/2 or PALB2 mutant pancreas cancer whose disease has progressed on front-line fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX) treated with nab-paclitaxel, gemcitabine, and cisplatin (NABPLAGEM) = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase II) II. To evaluate and compare overall survival (OS) time in patients with BRCA1/2 or PALB2 mutant whose disease has progressed on front-line FOLFIRINOX treated with 1) NABPLAGEM = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate and compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria between 2 treatment arms.

II. To evaluate and compare duration of response (DoR) between 2 treatment arms.

III. To evaluate and compare CA19-9 response (defined as patients with a baseline CA19-9 \>= 2x upper limit of normal (ULN) who demonstrate a minimum 25% decrease in CA19-9 at any time point) between 2 treatment arms.

IV. To evaluate and compare toxicity profile as assessed by treating clinicians between 2 treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive nab-paclitaxel intravenously (IV) over 30-40 minutes, gemcitabine IV over 30-40 minutes, and cisplatin IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study.

ARM II: Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study.

After completion of study treatment, patients are followed up within 30 days and then every 3 months for 2 years or until death, whichever comes first.

The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer

Phase II/III Second-Line NABPLAGEM vs. Nab-Paclitaxel/Gemcitabine in BRCA1/2 or PALB2 Mutant Metastatic Pancreatic Ductal Adenocarcinoma (PLATINUM)

Will be assessed by the proportion of patients who achieve complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) during the protocol treatment. Fisher's exact test will be conducted based on the first 32 patients in each arm who meet PP population criteria.

Will be conducted on modified intention-to-treat population. Stratified Cox model will be constructed to compare OS in the experimental arm to OS in the control arm.

Will be assessed per RECIST 1.1. Will be estimated, in each arm, using the method of Kaplan-Meier and compared by stratified Cox regression model.

The maximum grade for each type of adverse events that are possibly, probably, or definitely related to study treatments will be recorded for each patient.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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)
The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer	NCT06115499	Pancreatic Acin... Pancreatic Aden... Pancreatic Aden... Pancreatic Carc... Pancreatic Duct... Pancreatic Squa... Stage IV Pancre...	Nab paclitaxel Gemcitabine Cisplatin Magnetic Resona... Computed Tomogr... Biospecimen Col...	18 Years -	Alliance for Clinical Trials in Oncology
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)

Spots Global Cancer Trial Database for pancreatic squamous cell carcinoma