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

Phase 3

Completed

• Conditions: Metastatic Pancreatic Adenocarcinoma
• Interventions: Drug: Gemcitabine; Drug: Ibrutinib; Drug: Nab-paclitaxel

• Registration Number: NCT02436668
• Lead Sponsor: Pharmacyclics LLC.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-05-04
• Study First Submitted QC: 2015-05-06
• Study First Posted: 2015-05-07
• Primary Completion: 2018-10
• Study Completion: 2019-04-25
• Results First Submitted: 2019-10-31
• Results First Submitted QC: 2020-10-20
• Results First Posted: 2020-11-16
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-07
• Last Update Posted: 2020-12-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 430

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Nab-paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine
Placebo	Gemcitabine	Placebo daily in combination with: Nab-paclitaxel and gemcitabine
Ibrutinib	Ibrutinib	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine
Ibrutinib	Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine
Ibrutinib	Gemcitabine	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Results at an overall median follow-up of 24.87 months	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.
Overall Survival (OS)	Results at an overall median follow-up of 24.87 months	OS, is defined as the time from date of randomization until date of death from any cause.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Response	Results at an overall median follow-up of 24.87 months	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).
Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).	Results at an overall median follow-up of 24.87 months	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.
Overall Response Rate	Results at an overall median follow-up of 24.87 months	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.
Rate of Venous Thromboembolic Events (VTE)	Results at an overall median follow-up of 24.87 months	The VTE rate is defined as percentage of subjects with Venous thromboembolic events (SMQ) per investigator assessment.
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.	Results at an overall median follow-up of 24.87 months	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.
Carbohydrate Antigen 19-9 (CA19-9) Response	Results at an overall median follow-up of 24.87 months	The CA19-9 response rate is defined as the percentage of subjects with a decline of 20%, 90%, and other thresholds considered clinically meaningful, from baseline. This is a percentage of patients with \> or = 60% reduction from baseline.

Trial Locations

Locations (86)

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

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