Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies

NCT02109445 | Terminated Phase 2 Results DMC

• 2 other identifiers: A86410192013-005574-21
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 5

Brief Summary

This study consists of a Phase 1b portion aimed to determine the maximum tolerated dose and the safety profile of PF-03084014 in combination with gemcitabine and nab-paclitaxel followed by a Phase 2 portion to evaluate the efficacy of the triple combination in terms of overall survival in patients with metastatic pancreatic ductal adenocarcinoma not previously treated with anticancer therapies.

Conditions

Metastatic Cancer Pancreas

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1

  DLT was defined as any of the following events occurring during the first cycle of treatment and considered at least possibly-related to study medication: any Grade 3 or 4 clinically-relevant non-hematologic and/or hematologic toxicity, delay of more than 2 weeks in receiving the next scheduled cycle due to persisting treatment-related toxicities.

  Cycle 1 (28 days)

• Overall Survival (OS) in Phase 2

  Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

  From start of study treatment, collected every 3 months until death (up to 5 years)

Secondary Outcomes (28)

• Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 1

  Baseline up to 28-35 days post last administration of study drug

• Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 2

  Baseline up to 28-35 days post last administration of study drug

• Number of Participants With Laboratory Abnormalities in Phase 1

  Screening; Cycle 1 Days 1, 8, 15, 22; up to 28-35 days post last administration of study drug

• Number of Participants With Laboratory Abnormalities in Phase 2

  Screening; Days 1, 8, 15 of each cycle; up to 28-35 days post last administration of study drug

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Phases 1 and 2

  Baseline up to 28-35 days after treatment discontinuation

Study Arms (3)

Phase 1

EXPERIMENTAL

PF-03084014 in combination with gemcitabine and nab-paclitaxel

Drug: PF-03084014; Drug: Gemcitabine; Drug: Nab-paclitaxel

Phase 2 Arm A

EXPERIMENTAL

PF-03084014 in combination with gemcitabine and nab-paclitaxel

Drug: PF-03084014; Drug: Gemcitabine; Drug: Nab-paclitaxel

Phase 2 Arm B

ACTIVE COMPARATOR

Gemcitabine plus nab-Paclitaxel

Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

PF-03084014 DRUG

Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Doses: 100 -150 mg BID

Phase 1

Gemcitabine DRUG

Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.

Phase 1

Nab-paclitaxel DRUG

Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.

Also known as: Abraxane

Phase 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically diagnosis of metastatic ductal adenocarcinoma of the pancreas.
• No prior radiotherapy, surgery chemotherapy or investigational therapy for metastatic disease. Prior adjuvant therapy with 5-FU or gemcitabine (± gemcitabine post radiation) administered as radiosensitizer allowed, provided at least 6 months have elapsed between the last dose and study registration
• Tumor tissue available (Archival 6 months old or de novo biopsy)
• Measurable disease as per RECIST 1.1
• Performance Status (ECOG) 0 or 1

You may not qualify if:

• Symptomatic brain metastases requiring steroids
• Prior therapy with gamma secretase inhibitors or other Notch pathway inhibitor
• Major surgery within 4 weeks of registration in the current study
• Known hypersensitivity to gemcitabine or nab-paclitaxel or any of the excipients
• Current or anticipated need for food or drugs that are strong/moderate CYP3A4 inhibitors or inducers
• Diagnosis of any second malignancy within 3 years prior to registration

Sponsors & Collaborators

• Pfizer: lead
• Academic GI Cancer Consortium (AGICC): collaborator

Study Sites (5)

Anschutz Inpatient Pavilion

Aurora, Colorado, 80045, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Colorado Denver, CTO (CTRC)

Aurora, Colorado, 80045, United States

Location

University of Rochester Investigational Drug Pharmacy

Rochester, New York, 14642, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

nirogacestat; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Due to early termination of the study, only 3 participants were enrolled. Phase 2 was not carried out. As such, there is limited data for Phase 1 and no data for Phase 2.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 9, 2014
• Study Start: September 3, 2014
• Primary Completion: November 6, 2014
• Study Completion: November 6, 2014
• Last Updated: January 10, 2019
• Results First Posted: June 12, 2017

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share

Locations

US (5)