Olaparib and Durvalumab (MEDI4736) in Patients with Metastatic Pancreatic Cancer and DNA Damage Repair Genes Alterations

NCT05659914 | Active Not Recruiting Phase 2

• 2 other identifiers: TTD-20-042020-004859-32
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

Patients with metastatic pancreatic cancer and germline mutation in BRCA have benefit of therapy with PARP inhibitors. In addition, some studies have demonstrated that PDL-1 inhibitors synergize therapeutically with PARP inhibitors in tumours with homologous repair deficiency. Our hypothesis is that those patients with alterations in DNA damage repair genes (somatic and germline BRCA1, BRCA2, PALB2, RAD51C, RAD51D and other functional DDR genes) and who have benefit from platinum based therapy in first line might obtain an increased therapeutic effect with the combination of olaparib and durvalumab. This is an open-label, single-arm, multicentric phase II clinical trial of a combination of durvalumab and olaparib in patients with metastatic pancreatic cancer with alterations in DDR genes, who have had benefit with platinum-based chemotherapy in first line setting. The primary objective is to investigate the efficacy of this combination in terms of ORR. Patients will be eligible for the study based on alterations in a panel of specific DDR genes including BRCA1, BRCA2, PALB2, RAD51C, RAD51D and other DDR genes, as determined by a local assay according to local practice or by the central laboratory (if local assay is not available).

Conditions

Metastatic Pancreatic Cancer

Keywords

Metastatic Pancreatic Cancer; DDR genes; durvalumab; olaparib

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR defined as the percentage of patients with an investigator-assessed complete (CR) or partial response (PR) according to Response Evaluation Criteria in Solid tumours (RECIST) v1.1.

  Baseline through the end of the study (up 42 months)

Secondary Outcomes (5)

• Progression-free survival (PFS)

  Baseline through the end of the study (up 42 months)

• Overall survival (OS)

  42 months

• Duration of response (DoR)

  Baseline through the end of the study (up 42 months)

• Disease control rate (DCR)

  Baseline through the end of the study (up 42 months)

• Incidence and severity of AEs CTCAE v5 criteria

  Baseline through the end of the study (up 42 months)

Other Outcomes (1)

• To characterize the immune microenvironment of this tumours and biomarkers of HRD status, and RAD51 status in tumour tissue samples and blood samples

  Tumour tissue samples: at baseline and at progression and blood samples at baseline, on treatment and at progression

Study Arms (1)

olaparib +durvalumab

EXPERIMENTAL

olaparib+durvalumab

Drug: olaparib+durvalumab

Interventions

olaparib+durvalumab DRUG

olaparib: 300 mg tablets taken orally twice daily and durvalumab: 1500 mg via IV infusion q4w

olaparib +durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥18 years of age (at the time consent is obtained).
• Written informed consent provided.
• Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• Subject must have archival tumour tissue available for central laboratory testing of alterations in DDR genes or willing to undergo a fresh tumour biopsy.

You may not qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• Male or female patients 18 years of age or older, at the time of signing the ICF.
• Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas with alterations in DNA damage repair genes.
• Presence of alterations in DDR genes in tumour tissue previously determined by a local assay at any time prior to Screening or by the central laboratory.
• Patients must have received a minimum of 1 line of chemotherapy for advanced or metastatic disease and a maximum of 2 lines. Patients who have received adjuvant treatment and have recurrence within 6 months of completion of the adjuvant or neoadjuvant treatment, is counted as first line chemotherapy.
• Patients must have received platinum-based chemotherapy and must have benefit of it and not progressed while on platinum. Benefit is defined as partial or complete response or PFS ≥ 6 months.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days.
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
• Platelet count ≥ 100 x 109/L.
• Total serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN.
• International normalized ratio (INR) ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Total bilirubin ≤ 1.5 x ULN

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• AstraZeneca: collaborator

Study Sites (3)

Complejo Hospitalario Universitario La Coruña

A Coruña, Spain

Location

Hospital Universitari Vall d´Hebron

Barcelona, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Teresa Macarulla, MD

  Vall d'Hebron University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 21, 2022
• Study Start: November 28, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 18, 2024

Record last verified: 2024-10

Locations

ES (3)