A Phase II Multicentric Study of Olaparib in PALB2-related Advanced Pancreatic Cancer (PALBOLA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Di Modena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Nov 2024 → ongoing

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca S.p.A.

External identifiers

EU CT number

2024-516466-11-00

EudraCT number

2022-001094-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluation of the objective response rate (defined as CR and / or PR), carried out by radiological re-evaluation according to RECIST 1.1 criteria. An ORR> = 30% is expected.

Secondary objectives 1

1. Assessment of PFS (progression-free survival), DOR (duration of response), DCR (disease control rate), OS (overall survival), safety and tolerability of treatment. Furthermore, the quality of life will be assessed through the EORTC QLQ-C30 questionnaire.

Conditions and MedDRA coding

Locally advanced or metastatic pancreatic neoplasm with pathogenetic (C5) or possibly pathogenetic (C4) mutation of PALB2 found at the somatic or germinal level.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. A patient will be eligible for the study if they meet the following criteria: - Must be over 18 years of age - You must have histologically or cytologically confirmed pancreatic adenocarcinoma - Must have advanced disease (unresectable or metastatic) - Must have carried out genetic testing with evidence of a pathogenetic (C5) or probably pathogenetic (C4) mutation of PALB2 at the germinal or somatic level - Must have received at least one line of treatment for advanced (locally advanced or metastatic) disease. - Must have at least one measurable lesion according to RECIST 1.1 criteria by contrastenhanced CT (or MRI if the patient is allergic to the CT contrast medium). - Must have a life expectancy greater than 16 weeks according to the investigator's clinical judgment - Must have an ECOG PS equal to 0 or 1, established within 3 days of starting treatment - Must have adequate organ function at baseline (within 10 days of starting treatment) Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) in the screening period (within 24 hours of the first treatment dose) and confirmed on day 1 of each cycle. Male and female subjects of childbearing age must accept the use of an effective contraceptive method during treatment and for at least 1 month after (women) and 3 months after (men). Breastfeeding is not allowed during the study. - The patient (or legal representative) must have read and understood the informed consent and must have provided written informed consent.

Exclusion criteria 1

1. A patient is not eligible for study participation if one of the following criteria is met: - History of other malignant tumors in progress or requiring active treatments except: non-melanomatous skin carcinoma, ductal carcinoma in situ (DCIS); cervical cancer in situ; endometrial cancer G1, stage I; other solid tumors treated curatively without evidence of disease for> = 5 years - Presence of myelodysplastic syndrome / acute myeloid leukemia or suggestive elements for MDS / AML - Presence of symptomatic / uncontrolled CNS disease or presence of carcinomatous meningitis. - Weight loss> 10% during screening and / or decline in PS ECOG to> 1 between the baseline visit and 72 hours prior to the start of therapy - Presence of active infection that requires the initiation of systemic therapy - Presence of psychiatric pathology or substance abuse that may interfere with treatment compliance - Persistent CTCAE toxicity> Grade 2 caused by previous treatments with the exception of alopecia. Patients with CTCAE <= 2 sensorineural neuropathy due to previous oxaliplatin treatments may be included after consultation with the investigator. - Patients considered to be at high risk for uncontrollable medical events (e.g. ventricular arrhythmia, recent myocardial infarction, superior vena cava syndrome ...) - Inability to administer oral therapy or the presence of GI disorders that prevent the absorption of the study drug. - Immunocompromised patients (e.g. HIV) - Active hepatitis (B or C) - Presence of a benign variant or variant of uncertain significance (VUS) of PALB2 - Presence of other histology than ductal adenocarcinoma of the pancreas (e.g. neuroendocrine, adenosquamous, etc.) - Presence of bone disease alone as the site of metastatic disease - Major surgery within two weeks of starting treatment - Previous treatment with PARP inhibitor, including Olaparib - Previous systemic therapy, target therapy or radiotherapy (with the exception of palliation) within 3 weeks of starting the study - Treatment with potent CYP3A inhibitors (see protocol). A 2-week washout period is required - Treatment with potent CYP3A inducers (see protocol). A Version n.1 dated 09/02/2022 5 washout period of 5 weeks for enzalutamide and phenobarbital and 3 weeks for the other agents. - Whole blood transfusion in the last 120. Transfusion of platelets or concentrated red blood cells are allowed (no later than 28 days before the start of treatment) - Receiving allogeneic bone marrow transplant or double umbilical cord blood transplant (dUCBT) - Concomitant participation in another interventional clinical study or within the last 4 weeks - Known hypersensitivity to olaparib or to any of the excipients of the product - ECG indicating uncontrolled cardiac abnormalities or potentially reversible cardiac conditions in the opinion of the investigator - Any condition, therapy or laboratory alteration that may confuse trial data, interfere with trial participation, or make trial participation not the best treatment option for the patient - Involvement in planning / conducting the study - Patient deemed not compliant by the investigator - Patients pregnant woman, in the course of breastfeeding or who are considering a conception (also valid for male patients).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR), defined as the percentage of patients with response of either CR or PR.

Secondary endpoints 1

1. Assessment of PFS (progression-free survival), DOR (duration of response), DCR (disease control rate), OS (overall survival), safety and tolerability of treatment. Furthermore, the quality of life will be assessed through the EORTC QLQ-C30 questionnaire.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

Sponsor organisation

Azienda Ospedaliero Universitaria Di Modena

Address

Largo Del Pozzo 71

City

Modena

Postcode

41124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Andrea Spallanzani

Public contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Andrea Spallanzani

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications