NCT05412706

Niraparib Maintenance Treatment in mCRC With a Partial o Complete Response After Oxaliplatin-based Induction Therapy

Niraparib Maintenance Treatment in Metastatic Colorectal Cancer Patients With a Partial or Complete Response After Oxaliplatin-based Induction Therapy: Bohème Trial

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Ospedale Policlinico San Martino · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Colorectal Cancer ranks third among the most frequent malignancies representing a leading cause of cancer-related death worldwide. The constant improvement in the "continuum of care" of metastatic colorectal cancer (mCRC) patients led to a median overall survival of about 30-36 months. Due to the cumulative toxicities of first-line combinations of chemotherapy and biological agents, discontinuation or intermittent chemotherapy or maintenance strategies have been investigated in clinical trials. After a 4 to 6-month induction treatment with bevacizumab plus doublet or triplet regimens, a fluoropyrimidine plus bevacizumab is regarded as the optimal maintenance regimen. Little evidence is available on the role of maintenance with anti-EGFR agents. A recent systematic review and network meta-analysis of 12 relevant randomized clinical trials comprising 5540 patients with mCRC showed that a maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear overall survival benefit, shared decision-making should include observation as an acceptable alternative. Poly(ADP)-ribose polymerase (PARP) inhibitors are now approved for breast, ovarian and pancreatic cancers. Evidence suggests that PARP inhibitors are more effective in tumors harboring homologous recombination DNA damage repair (HRR) deficiency and platinum sensitivity may be used a surrogate marker of HRD and therefore of PARP-inhibitors efficacy. An extensive Next Generation Sequencing analysis revealed that 15% of mCRC samples harbors mutations in genes involved in the HRR pathway. Several clinical trials are ongoing to test PARP inhibitors either alone or in combination in mCRC patients. The originality of this trial is to investigate PARPi in the maintenance setting. Pre-clinical evidence showed that PARP blockade after initial oxaliplatin response delayed disease progression in mCRC carrying Kirsten Rat Sarcoma and BRAF mutations, suggesting that maintenance treatment with PARP inhibitors warrants further clinical investigation in mCRC patients who respond to oxaliplatin-containing induction treatment. The main objective of this trial is to investigate the efficacy of anti-PARP inhibition as maintenance treatment in mCRC patients who obtained a complete or partial response after 4-month induction treatment with oxaliplatin-based double or triplet plus biologic agents.

Detailed description

Multicenter phase II no profit study investigating the disease-free survival efficacy of niraparib as maintenance treatment in 46 patients with metastatic colorectal cancer with partial or complete response after oxaliplatin-based induction therapy. The study also includes translational research objectives.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Niraparib	Patients will receive Niraparib 200-300 mg orally as an individualized weight and platelet-based, flat-fixed, continuous daily dose. Niraparib will be administered orally once daily in 28-day cycles.

Timeline

• Start date: 2023-09-04
• Primary completion: 2023-09-04
• Completion: 2023-09-04
• First posted: 2022-06-09
• Last updated: 2023-09-08