Cisplatin to Patients With Pancreatic Cancer and Homologous Recombination Deficiency

Pancreatic Adenocarcinoma Clinical Trial

— PTCA199-6  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06095141
• Other study ID #: PTCA199-6
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 1, 2023
• Est. completion date: October 31, 2026

Study information

• Verified date: December 2023
• Source: Fudan University
• Contact: Ying Yang, MD
• Phone: 86 64175590
• Email: yangying[@]fudanpci.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Homologous Recombination Deficiency
• Pancreatic Adenocarcinoma

Intervention

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.

Locations

Country	Name	City	State
China	Shanghai Cancer Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

References & Publications (2)

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-M — View Citation

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 Gemcitab — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	objective response rate (ORR)	CR + PR	At the end of Cycle 1 (each cycle is 21 days)
Secondary	disease control rate (DCR)	CR + PR + SD	At the end of Cycle 1 (each cycle is 21 days)
Secondary	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)