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 LLC.430 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

430

Conditions

Metastatic Pancreatic Adenocarcinoma

Interventions

IbrutinibDRUG

GemcitabineDRUG

Nab-paclitaxelDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (86)

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

PFS is defined as the time from the date of randomization until disease progression per RECIST 1.1 criteria assessed by investigator, or death from any cause, whichever occurs first.

Time frame: Results at an overall median follow-up of 24.87 months

Overall Survival (OS)

OS, is defined as the time from date of randomization until date of death from any cause.

Time frame: Results at an overall median follow-up of 24.87 months

Secondary Outcomes

Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine.

This is a measure of percentage of subjects with Treatment Emergent Adverse Events Grade 3 or above collected Up to 30 days after the last participating subject discontinues study drug.

Time frame: Results at an overall median follow-up of 24.87 months

Overall Response Rate

ORR is defined as the percentage of subjects who achieve a complete response or partial response, based on investigator assessment according to RECIST 1.1.

Time frame: Results at an overall median follow-up of 24.87 months

Clinical Benefit Response

Subject achieved a ≥50% reduction in pain intensity (Memorial Pain Assessment Card \[MPAC\]) or analgesic consumption, or a 20-point or greater improvement in KPS for a period of at least 4 consecutive weeks, without showing any sustained worsening in other parameters. OR Subject was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain (≥7% increase maintained for ≥4 weeks) not due to fluid accumulation (Burris 1997).

Time frame: Results at an overall median follow-up of 24.87 months

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Oncology Specialties, PC; Clearview Cancer Institute

Huntsville, Alabama, United States

Arizona Center for Cancer Care

Avondale, Arizona, United States

St. Mary's Medical Center

Daly City, California, United States

Moores UCSD Cancer Center

La Jolla, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Norwalk Hospital

Norwalk, Connecticut, United States

Eastern Connecticut Hematology/Oncology Assoc.

Norwich, Connecticut, United States

Bethesda Memorial Hospital

Boynton Beach, Florida, United States

Florida Hospital Tampa

Tampa, Florida, United States

University Cancer & Blood Center, LLC

Athens, Georgia, United States

...and 76 more locations

Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).

Unit is the month: TUDD1 - the time between random \& 1st occurrence of a decrease in QLQ-C30 score ≥10 pts w/o improvement in QoL score of ≥10 points or any further QoL data due to deterioration. The proportion of subjects who met the "responder" criteria prior to subsequent anticancer therapy initiation. Response defined as achievement of a ≥50% reduction in MPAC visual analog scale which measures pain intensity or analgesic consumption, or a ≥20-point improvement from baseline in KPS sustained for a period of ≥ 4 consecutive weeks without showing any sustained worsening from baseline in any of the other parameters OR Subject stable on all parameters (pain and KPS), \& showed a marked, sustained weight gain (≥7% increase from baseline maintained for ≥4 weeks) not due to fluid accumulation.

Time frame: Results at an overall median follow-up of 24.87 months