Cisplatin to Patients With Pancreatic Cancer and Homologous Recombination Deficiency (PTCA199-6)

Cisplatin Based Regimen to Patients With Advanced Pancreatic Cancer and Homologous Recombination Deficiency

The purpose of this study is to evaluate the efficacy of cisplatin based regimen to patients with advanced pancreatic cancer and homologous recombination deficiency.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Adenocarcinoma; Homologous Recombination Deficiency
• Intervention / Treatment: Drug: Cisplatin

Detailed Description

Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy with a 5-year survival less than 10%. Approximately 80% of patients with pancreatic cancer are diagnosed at an advanced stage. Chemotherapy is one of the major treatments for advanced pancreatic cancer. In 2011, the PRODIGE trial has shown that oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) was associated with a survival advantage but had increased toxicity.

Defects in DNA damage response (DDR) genes causing homologous recombination deficiency (HRD) identify a clinically relevant subgroup of patients with PDAC, with both therapeutic and preventative implications. Accumulating evidence from nonrandomized and randomized clinical trials suggests HRD as a putative biomarker of therapeutic response for platinum-based chemotherapy in patients with advanced PDAC. Within HRD, germline variants in BRCA1 and BRCA2 are associated with improved progression-free survival in patients with platinum-sensitive metastatic PDAC treated with the poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib as maintenance therapy. Interestingly, based on preclinical evidence and phase II nonrandomized clinical trials, additional non-BRCA HRD aberrations may predict sensitivity to PARPi with other therapeutic strategies targeting DDR currently under clinical investigation (including immunotherapy, ATM, ATR, and PALB2 inhibitors). However, the efficacy of cisplatin based regimen as a second line treatment for patients with HRD has not been systematically studied.

The purpose of this study is to evaluate the efficacy of cisplatin based regimen on improving the progression-free survival (PFS) of advanced pancreatic cancer patients who harbor germline or somatic homologous recombination deficiency. These patients are resistant to at least one line of systemic chemotherapy. PFS, objective response rate (ORR), overall survival (OS) and disease control rate (DCR) are measured every four weeks.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ying Yang, MD; Phone Number: 1307 86 64175590; Email: yangying@fudanpci.org

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Cancer Center
    • Contact: Ying Yang, MD; Phone Number: 1307 86 21 64175590; Email: yangying@fudanpci.org
    • Principal Investigator: Guopei Luo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥ 18 years and ≤ 80 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Histologically or cytologically confirmed advanced pancreas adenocarcinoma.
• Tumor progression after at least one line of chemotherapy.
• Genetic or molecular test confirmed the presence of homologous recombination deficiency.
• Presence of at least of one measurable lesion in agreement to RECIST criteria.
• The expected survival ≥ 3 months.
• Adequate organ performance based on laboratory blood tests.
• Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria:

• Pregnant or nursing women.
• Primary pancreatic cancer.
• Patients who have received platinum or PARPi treatment.
• The diagnosis was confirmed by pathology as non-adenocarcinoma of pancreas.
• Inflammation of the digestive tract, including pancreatitis, cholecystitis, cholangitis, etc.
• Severe and uncontrollable accompanying diseases that may affect protocol compliance or interfere with the interpretation of results.
• Renal insufficiency or dialysis
• Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment.
• Patients who are allergic to cisplatin or other platinum drugs.
• Patients who are unwilling or unable to comply with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cisplatin; Cisplatin 25 mg/m2, ivgtt, 30 min, D1, 8.

Drug: Cisplatin; Cisplatin 25 mg/m2, ivgtt, 30 min, D1, 8. The administration of other chemotherapeutic agents including gemcitabine, nab-paclitaxel, fluorouracil, irinotecan, capecitabine is applied according to the National Comprehensive Cancer Network (NCCN) guideline. PARP inhibitor will be recommended to patients with platinum-sensitive metastatic PDAC after six months of cisplatin based regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival, PFS	PFS of subjects from recruiting to the time of disease progression	At the end of Cycle 1 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	CR + PR	At the end of Cycle 1 (each cycle is 21 days)
disease control rate (DCR)	CR + PR + SD	At the end of Cycle 1 (each cycle is 21 days)
Overall survival，OS	OS of subjects from recruiting to the time of death from any cause	At the end of Cycle 1 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Fudan University

Publications and helpful links

General Publications

• O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen DP. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 1;38(13):1378-1388. doi: 10.1200/JCO.19.02931. Epub 2020 Jan 24.
• Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algul H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. doi: 10.1056/NEJMoa1903387. Epub 2019 Jun 2.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: PTCA199-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No