NABPLAGEM versus nab-paclitaxel plus gemcitabine for BRCA1/2- or PALB2-mutated metastatic pancreatic cancer

Comparing Second-Line NABPLAGEM vs. Nab-paclitaxel/Gemcitabine in BRCA1/2 or PALB2 Mutant Metastatic Pancreatic Ductal Adenocarcinoma

This trial will test whether the NABPLAGEM regimen works better than standard nab-paclitaxel plus gemcitabine for people with BRCA1/2 or PALB2 mutated metastatic pancreatic cancer whose disease progressed after first-line FOLFIRINOX.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06783140 on ClinicalTrials.gov

What this trial studies

This phase 2/3 trial compares an investigational NABPLAGEM regimen with standard nab-paclitaxel plus gemcitabine in patients who have BRCA1/2 or PALB2 mutated metastatic pancreatic cancer and measurable disease after progression on first-line FOLFIRINOX (or NALIRIFOX). Eligible participants are treated and followed for tumor response, progression-free survival, and safety outcomes. One arm receives NABPLAGEM, which includes nab-paclitaxel and gemcitabine with the addition of cisplatin, while the control arm receives the standard nab-paclitaxel plus gemcitabine combination. Patients must have recovered from recent treatment-related toxicities and be able to attend the treating centre for therapy and assessments.

Who should consider this trial

Good fit: Ideal candidates have metastatic pancreatic adenocarcinoma (including certain histologic variants), a somatic or germline BRCA1/2 or PALB2 mutation, measurable disease, and documented progression on first-line FOLFIRINOX (or NALIRIFOX).

Not a fit: Patients without BRCA1/2 or PALB2 mutations, those with earlier-stage disease, or those who have not progressed on first-line FOLFIRINOX are unlikely to benefit from this mutation-targeted comparison.

Why it matters

Potential benefit: If successful, this approach could improve response rates and extend the time patients with BRCA1/2 or PALB2 mutations live without disease worsening compared with the current standard regimen.

How similar studies have performed: Platinum-containing chemotherapies and PARP-targeted strategies have shown activity in BRCA/PALB2-mutated pancreatic cancer, but direct evidence for this exact NABPLAGEM combination versus nab-paclitaxel/gemcitabine is limited.

Eligibility criteria

Inclusion Criteria:

* Metastatic pancreatic adenocarcinoma. Adenosquamous carcinoma, squamous carcinoma, acinar cell carcinoma, and carcinoma not otherwise specified are also acceptable.
* BRCA1/2 or PALB2 mutation (somatic or germline).
* Measurable disease.
* Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
* Clinical or radiographic progression on first-line FOLFIRINOX (or NALIRIFOX) for metastatic disease.

  * Patients whose front-line chemotherapy was required to be simplified due to toxicity associated with any of the constituent components of FOLFIRINOX/NALIRIFOX (e.g. simplified to FOLFOX, FOLFIRI, 5-FU (including capecitabine)) will be eligible.
  * Patients with progressive disease while on maintenance PARP inhibitor treatment after FOLFIRINOX (or NALIRIFOX), irrespective of how long ago they received FOLFIRINOX/NALIRIFOX, will also be eligible.
  * Patients who develop metastatic disease during or within 6 months after completing FOLFIRINOX/NALIRIFOX in either the locally advanced or adjuvant/neoadjuvant settings will be eligible.
* Age 18 years or older.
* Ability to understand and willing to sign a written informed consent document.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (Karnofsky Performance Status ≥60).
* Required Initial Laboratory Values
* Not pregnant and not nursing.

Exclusion Criteria:

* Patients may not have received prior cisplatin for their pancreatic cancer in any setting.
* Patients with \> grade 2 peripheral sensory neuropathy are not eligible.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 8-weeks. Patients with known, new or progressive brain metastases (active brain metastases) or leptomeningeal disease are ineligible.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load anytime within 6 months prior to registration are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Concomitant Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.

Where this trial is running

Toronto, Ontario

• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Erica S Tsang, MD — Princess Margaret Cancer Centre/University Health Network
• Study coordinator: Erica S Tsang, MD

Conditions Pancreatic Cancer, Advanced or Metastatic; BRCA1/2 Mutation; PALB2 Gene Mutation