Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients

NCT ID: NCT02732938

Last Updated: 2019-02-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-04
• Study Completion Date: 2017-10-10

Brief Summary

The purpose of this Phase 1b/2 study is to evaluate the safety and tolerability of PF-04136309 in combination with nab-paclitaxel and gemcitabine, characterize the dose-limiting toxicities (DLTs) and overall safety profile of escalated doses of PF-04136309 and the associated schedule, determine the maximum tolerated dose (MTD), and to assess the enhancement of efficacy of PF-04136309 in combination with nab-paclitaxel and gemcitabine versus nab-paclitaxel + gemcitabine + placebo in terms of Progression Free Survival.

Detailed Description

The study has 2 parts:

Phase 1b (dose-finding cohorts) will be open label as patients will receive ascending doses of PF-04136309 in combination with nab-paclitaxel + gemcitabine. The observation period for dose-limiting toxicities (DLTs) will be from Day 1 to Day 28. Pharmacokinetic (PK) and pharmacodynamic (PD) properties of PF-04136309 will also be assessed. The criteria for dose escalation will be based on a modified toxicity probability interval (mTPI) method. After evaluating the safety and other results (eg, PK) from patients enrolled in the dose escalation cohorts, a dose level will be selected to be further evaluated as the Recommended Phase 2 Dose (RP2D). A minimum of 6 patients, up to 12 patients, will be treated at this dose level to establish it as the RP2D. To further evaluate safety and pharmacodynamics, the number of patients enrolled during this part of the study (Phase 1b) may be N up to 20. The study will stop if all PF-04136309 doses explored appear to be overly toxic.

Phase 2 randomized double blinded placebo control. Approximately 92 patients will be randomized 1:1 to receive the RP2D of PF-04136309 in combination with nab-paclitaxel + gemcitabine (ARM A; n=46) versus nab-paclitaxel + gemcitabine + placebo (ARM B; n=46). The primary objective will be the enhancement of efficacy in terms of PFS.

Patients will be treated as long as they are clinically benefiting from investigational product without unacceptable toxicity, objective disease progression, or withdrawal of consent.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PF-04136309 + Nab-p + Gem

PF-04136309 oral dosing

Nab-paclitaxel IV dosing Gemcitabine IV dosing

Group Type: EXPERIMENTAL

PF-04136309

Intervention Type: DRUG

PF-04136309 oral dosing

Nab-paclitaxel

Intervention Type: DRUG

Nab-paclitaxel IV dosing

Gemcitabine

Intervention Type: DRUG

Gemcitabine IV dosing

Interventions

PF-04136309

PF-04136309 oral dosing

Intervention Type: DRUG

Nab-paclitaxel

Nab-paclitaxel IV dosing

Intervention Type: DRUG

Gemcitabine

Gemcitabine IV dosing

Intervention Type: DRUG

Other Intervention Names

Abraxane; Gemzar

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically proven diagnosis of metastatic ductal adenocarcinoma of the pancreas.

2. All patients must provide a baseline tumor sample at registration. If an archival sample is not available, patients must have a metastatic biopsy collected at the screening visit.

3. Patient must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.

4. Measurable disease as per RECIST v. 1.1.

5. Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 NCI CTCAE.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

7. Age ≥18 years.

8. Adequate Bone Marrow, Renal and liver Functions.

Exclusion Criteria

1. Patients with known symptomatic brain metastases requiring steroids.

2. Prior therapy with modulators of monocyte or TAM function.

3. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks of registering for the current study and/or during study participation.

4. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma or in situ cervical carcinoma.

5. Known hypersensitivity to nab-paclitaxel or to gemcitabine or to any of the excipients.

6. Any one of the following currently or in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack; symptomatic pulmonary embolism; congenital long QT syndrome, torsades de points, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, atrial fibrillation of any grade, or QTc interval >470 msec at screening.

7. Concurrent administration of herbal preparations.

8. Use of oral anticoagulants. Use of subcutaneous anti coagulation is allowed. Concurrent use of potent or moderate inhibitors or inducers of CYP3A4 and/or CYP2C8.

9. Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.

10. History of interstitial lung disease, or slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

11. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior) or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.

12. Pregnant female patients; breastfeeding female patients; males patients with partners currently pregnant, male patients able to father children and female patients of childbearing potential who are unwilling or unable to use two (2) highly effective methods of contraception as outlined in this protocol for the duration of the study and for 28 days after last dose of PF-04136309, and for 6 months after last dose of nab-paclitaxel, gemcitabine, or both.

13. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Rochester Cancer Center Pharmacy

Rochester, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Sampson Regional Medical Center

Clinton, North Carolina, United States

Southeastern Medical Oncology Center

Clinton, North Carolina, United States

Southeastern Medical Oncology Center

Goldsboro, North Carolina, United States

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Onslow Memorial Hospital

Jacksonville, North Carolina, United States

Southeastern Medical Oncology Center

Jacksonville, North Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

MUSC Hollings Cancer Center

Charleston, South Carolina, United States

MUSC Health East Cooper

Mt. Pleasant, South Carolina, United States

MUSC Health North Charleston

North Charleston, South Carolina, United States

Countries

United States

References

Noel M, O'Reilly EM, Wolpin BM, Ryan DP, Bullock AJ, Britten CD, Linehan DC, Belt BA, Gamelin EC, Ganguly B, Yin D, Joh T, Jacobs IA, Taylor CT, Lowery MA. Phase 1b study of a small molecule antagonist of human chemokine (C-C motif) receptor 2 (PF-04136309) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic ductal adenocarcinoma. Invest New Drugs. 2020 Jun;38(3):800-811. doi: 10.1007/s10637-019-00830-3. Epub 2019 Jul 12.

Reference Type: DERIVED

PMID: 31297636 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A9421018&StudyName=Phase%201b%2F2%20Study%20Of%20Pf-04136309%20In%20Combination%20With%20Gemcitabine%20And%20Nab-paclitaxel%20In%20Patients%20With%20Previously%20Untreated%20Metastatic%20Pancreatic%20Ductal%20Adenocarcinoma

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

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A9421018&StudyName=Phase+1b%2F2+Study+Of+Pf-04136309+In+Combination+With+Gemcitabine+And+Nab-paclitaxel+In+Patients+With+Previously+Untreated+Metastatic+Pancreatic+Ductal+Adenocarcinoma

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

Other Identifiers

2015-003767-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

A9421018

Identifier Type: -

Identifier Source: org_study_id