Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)

Pharmacyclics

Status and phase: Completed; Phase 3

Conditions: Metastatic Pancreatic Adenocarcinoma

Treatments: Drug: Nab-paclitaxel; Drug: Ibrutinib; Drug: Gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02436668

PCYC-1137-CA

Details and patient eligibility

About

This is a phase 3 study to evaluate the efficacy of ibrutinib in combination with nab-paclitaxel and gemcitabine for the first line treatment of patients with metastatic pancreatic adenocarcinoma.

Enrollment: 430 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma.

2. Stage IV disease diagnosed within 6 weeks of randomization

3. Adequate hematologic function:

   • Absolute neutrophil count (ANC) ≥1.5 x 109/L
   • Platelet count ≥100 x 109/L
   • Hemoglobin ≥9 g/dL

4. Adequate hepatic and renal function defined as:

   • AST and/or ALT ≤5.0 x upper limit of normal (ULN) if liver metastases, or ≤3 x ULN without liver metastases
   • Alkaline phosphatase <3.0 x ULN or ≤5.0 x ULN if liver or bone metastases present
   • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, such as hemolysis)
   • Estimated Creatinine Clearance ≥30 mL/min

5. PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN

6. KPS ≥70.

7. Eastern Cooperative Oncology Group (ECOG) 0-1

Exclusion criteria

1. Prior therapies: BTK inhibitor, radiotherapy, radiotherapy in the adjuvant setting, or cytotoxic chemotherapy for primary disease of pancreatic adenocarcinoma.
2. Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma
3. Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
4. Major surgery within 4 weeks of first dose of study drug.
5. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
6. Treatment with a strong cytochrome P450 (CYP) 3A inhibitor.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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430 participants in 2 patient groups, including a placebo group

Ibrutinib

Active Comparator group

Description:

Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine

Treatment:

Drug: Nab-paclitaxel

Drug: Ibrutinib

Drug: Gemcitabine

Placebo

Placebo Comparator group

Description:

Placebo daily in combination with: Nab-paclitaxel and gemcitabine

Treatment:

Drug: Nab-paclitaxel

Drug: Gemcitabine