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

Study Overview

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

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.

Pancreatic Acinar Cell Carcinoma
Pancreatic Adenosquamous Carcinoma
Pancreatic Squamous Cell Carcinoma
Resectable Pancreatic Acinar Cell Carcinoma
Resectable Pancreatic Adenocarcinoma
Resectable Pancreatic Adenosquamous Carcinoma
Resectable Pancreatic Carcinoma

PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
PROCEDURE: Magnetic Resonance Imaging
DRUG: Olaparib
DRUG: Placebo Administration

NCI-2020-05659
NCI-2020-05659 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
EA2192 (OTHER Identifier) (OTHER: ECOG-ACRIN Cancer Research Group)
EA2192 (OTHER Identifier) (OTHER: CTEP)
U10CA180820 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-04-23	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-10-14
First Submitted that Met QC Criteria 2021-04-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2025-10-15
First Posted (ESTIMATED) 2021-04-26	Results First Posted N/A	Last Verified 2025-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
Double

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm I (olaparib) 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 stud	PROCEDURE: Biospecimen Collection Undergo collection of blood PROCEDURE: Computed Tomography Undergo CT or CT/MRI PROCEDURE: Magnetic Resonance Imaging Undergo CT/MRI DRUG: Olaparib Given PO
PLACEBO_COMPARATOR: Arm II (placebo) 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	PROCEDURE: Biospecimen Collection Undergo collection of blood PROCEDURE: Computed Tomography Undergo CT or CT/MRI PROCEDURE: Magnetic Resonance Imaging Undergo CT/MRI DRUG: Placebo Administration Given PO

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm I (olaparib)

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 stud

PROCEDURE: Biospecimen Collection

Undergo collection of blood

PROCEDURE: Computed Tomography

Undergo CT or CT/MRI

PROCEDURE: Magnetic Resonance Imaging

Undergo CT/MRI

DRUG: Olaparib

Given PO

PLACEBO_COMPARATOR: Arm II (placebo)

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

PROCEDURE: Biospecimen Collection

Undergo collection of blood

PROCEDURE: Computed Tomography

Undergo CT or CT/MRI

PROCEDURE: Magnetic Resonance Imaging

Undergo CT/MRI

DRUG: Placebo Administration

Given PO

Primary Outcome Measures	Measure Description	Time Frame
Improvement in relapse-free survival (RFS)	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.	From randomization to first documentation of disease recurrence (primary tumor relapse) or death, assessed from 22 months to 44 months

Secondary Outcome Measures	Measure Description	Time Frame
RFS	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.	From randomization to first documentation of disease recurrence (primary tumor relapse) or death, assessed up to 5 years
Overall survival (OS)	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.	From randomization until 10 years after registration or until death, whichever comes first
Efficacy of olaparib after chemotherapy in patients with a pathogenic germline BRCA or PALB2 mutation	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.	Up to 10 years
Differences in survival	Will analyze survival differences between patients who received neoadjuvant or perioperative chemotherapy compared to those who received adjuvant therapy alone.	Up to 10 years
RFS in those who received =< 3 months of perioperative platinum chemotherapy compared to > 3 months of perioperative platinum chemotherapy	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.	From randomization to first documentation of disease recurrence (primary tumor relapse) or death, assessed up to 5 years
OS in those who received =< 3 months of perioperative platinum chemotherapy versus > 3 months of perioperative platinum chemotherapy	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.	From randomization until 10 years after registration or until death, whichever comes first
RFS in those who received any platinum-based perioperative chemotherapy versus no platinum-based perioperative chemotherapy	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.	From randomization to first documentation of disease recurrence (primary tumor relapse) or death, assessed up to 5 years
OS in those who received any platinum-based perioperative chemotherapy versus no platinum-based perioperative chemotherapy	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.	From randomization until 10 years after registration or until death, whichever comes first

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

STEP 0 (PRE-REGISTRATION) INCLUSION CRITERIA
Patient must be >= 18 years of age on day of consent
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Patient must have a diagnosis of pancreatic cancer and have successfully undergone a curative intent surgical resection and must have no evidence of recurrent disease as determined by the investigator

NOTE: This includes patients with adenocarcinoma, acinar carcinoma, squamous cell carcinoma adenosquamous and variants thereof. Patients with neuroendocrine tumors are excluded from enrolling
Patient must (1) be planning to receive, (2) be receiving or (3) have received at least three combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 month course)
Patient must be no more than 12 weeks from their most recent treatment (this may be chemotherapy, radiotherapy or surgery)
Patient must have a known pathogenic or likely pathogenic germline or somatic mutation in BRCA1, BRCA2, or PALB2, as determined by a Clinical Laboratory Improvement Amendments (CLIA) certified or equivalently-accredited laboratory. Mutations must be considered pathogenic or likely pathogenic by a reference database such as ClinVar or OncoKb.org
STEP 1 (RANDOMIZATION) INCLUSION CRITERIA
Patient must have met the eligibility criteria outlined above
Patient must have undergone at least 3 combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 months course)
Central expert reviewer must have determined the patient eligible for randomization after review of local genetic testing reports
If mutation in BRCA1, BRCA2 or PALB2 was identified in tumor tissue and the patient has not previously undergone germline testing, the patient must agree to undergo germline testing
Patient must have no evidence of recurrent or metastatic pancreatic cancer at the time of randomization as documented by baseline scans obtained =< 4 weeks prior to Step 1 randomization
Patient must not have previously had evidence of progressive pancreatic cancer while receiving platinum-based therapy
Patient must be >= 21 days (three weeks) from their last treatment (including chemotherapy radiotherapy or surgery) but =< 84 days (twelve weeks) from their last treatment at the time of Step 1 randomization. Patients who have received neoadjuvant and/or adjuvant radiotherapy are eligible
Patient must have recovered from any adverse events due to prior anti-cancer therapy (i.e., have no residual toxicities > grade 1 with the exception of alopecia and/or neuropathy)
Patient must not be receiving any other investigational agents at the time of Step 1 randomization and while on protocol treatment
Patient must not have any history of allergic reactions attributed to compounds of similar chemical or biological composition to olaparib
Patient must not have any personal history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
Patient must not have any uncontrolled gastrointestinal disorder that would, in the opinion of the investigator, interfere with the ingestion or absorption of olaparib
Patient must not be pregnant or breast-feeding due the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment for female patients and for 3 months after the last dose of protocol treatment for male patients. Patients must also not donate sperm while on protocol treatment and for 3 months after the last dose of protocol treatment. Patients must also not breast-feed while on protocol treatment and for 1 month after the last dose of protocol treatment
Leukocytes >= 3,000/mcL (obtained =< 28 days prior to Step 1 randomization)
Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to Step 1 randomization)
Platelets >= 100,000/mcL (obtained =< 28 days prior to Step 1 randomization)
Hemoglobin >= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =< 28 days prior to Step 1 randomization)
Total bilirubin =< 1.5 institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin =< 2.5 x ULN of the direct bilirubin (obtained =< 28 days prior to Step 1 randomization)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 institutional ULN (obtained =< 28 days prior to Step 1 randomization)
Creatinine =< 1.5 institutional ULN OR calculated Cockcroft Gault creatinine clearance > 50 mL/min/1.73 m^2 (obtained =< 28 days prior to Step 1 randomization)
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patient must not have resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT [QTc] prolongation > 500 ms, electrolyte disturbances, etc.) or have congenital long QT syndrome
Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir is prohibited
Patients who are being actively treated for an ongoing concurrent malignancy are ineligible, with the exception of those receiving adjuvant hormone therapies and those receiving topical therapies for skin cancers
Patient must not have, in the opinion of the investigator, any other concurrent medical condition that would prevent the patient from complying with the study procedures
Patient must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
Patient must have the ability to understand and the willingness to sign a written informed consent document, or have legally authorized representative provide authorization to participate
Patient must not have had major surgery within 2 weeks prior to Step 1 randomization and patients must have recovered from any effects of any major surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Kim A Reiss Binder, ECOG-ACRIN Cancer Research Group

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Conroy T, Lambert A, Ducreux M. Adjuvant and neoadjuvant approaches in pancreatic cancer. Curr Opin Oncol. 2023 Jul 1;35(4):326-333. doi: 10.1097/CCO.0000000000000962. Epub 2023 May 12.

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