Dose Escalation Study Of OMP-54F28 In Combination With Nab-Paclitaxel And Gemcitabine In Patients With Previously Untreated Stage IV Pancreatic Cancer

Study Overview

Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with nab-paclitaxel and gemcitabine. OMP-54F28 will be administered IV on Days 1 and 15 of each 28-day cycle. Nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be administered IV on Days 1, 8, and 15 of each cycle. The planned dose levels of OMP-54F28 are 3.5 mg/kg and 7.0 mg/kg.

Depending on safety in this study, additional lower or intermediate dose levels may be evaluated. Depending on emerging safety data from the Phase 1a study 54F28-001 with continuing dose escalation, additional higher dose levels of OMP-54F28 may be evaluated in this study. No dose escalation of OMP-54F28 will be allowed within a dose cohort. Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined, up to 10 patients may be enrolled in the cohort-expansion phase to better characterize the safety, tolerability and PK of OMP-54F28 combined with nab-paclitaxel and gemcitabine. Up to approximately 34 patients may be enrolled into the study.

Pancreatic Cancer
Stage IV Pancreatic Cancer

DRUG: OMP-54F28, Nab-Paclitaxel and Gemcitabine

54F28-002

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-01-28	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-09-07
First Submitted that Met QC Criteria 2014-01-28	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-09-09
First Posted (ACTUAL) 2014-01-30	Results First Posted N/A	Last Verified 2020-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Drug: OMP-54F28, Nab-Paclitaxel and Gemcitabine	DRUG: OMP-54F28, Nab-Paclitaxel and Gemcitabine

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Drug: OMP-54F28, Nab-Paclitaxel and Gemcitabine

DRUG: OMP-54F28, Nab-Paclitaxel and Gemcitabine

Primary Outcome Measures	Measure Description	Time Frame
Safety and tolerability of OMP-54F28 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated Stage IV pancreatic cancer	The maximum tolerated dose (MTD) will be determined in patients treated with gemcitabine in combination with weekly nab-paclitaxel (from Day 0 - 28)	Subjects will be treated and observed for DLT through the end of the first cycle (from Day 0 - 28)

Secondary Outcome Measures	Measure Description	Time Frame
Pharmacokinetics (PK) of OMP-54F28 when administered in combination with nabpaclitaxel and gemcitabine to patients with previously untreated Stage IV pancreatic cancer	Apparent half life, AUC, clearance, volume of distribution	Plasma sample for Pharmacokinetics (PK) analysis to be obtained prior to the gemcitabine infusion and before nabpaclitaxel infusion from Day 0 to treatment termination

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Signed Informed Consent Form
Age ≥18 years
Histologically documented Stage IV ductal adenocarcinoma of the pancreas
Availability of FFPE tumor tissue, either archival or obtained at study entry through fresh biopsy
Tumor tissue from fine needle aspiration is not acceptable.
ECOG performance status of 0 or 1
Adequate hematologic and end-organ function
Evaluable or measurable disease per RECIST v1.1
For women of childbearing potential and men with partners of childbearing potential, agreement to use two effective forms of contraception

Prior therapy before Day 1 of Cycle 1 for the treatment of Stage IV pancreatic cancer
Prior adjuvant therapy for the treatment of ductal adenocarcinoma of the pancreas
Known hypersensitivity to any component of study treatments
Known brain metastases, uncontrolled seizure disorder, or active neurologic disease
Leptomeningeal disease as a manifestation of cancer
Active infection requiring antibiotics
Bisphosphonate therapy for symptomatic hypercalcemia
Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis
Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
Pregnancy, lactation, or breastfeeding
Known HIV infection
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Concurrent use of therapeutic warfarin
History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis
New York Heart Association Classification III or IV
Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study
Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan
Bone metastases and one of the following:

Prior history of a pathologic fracture
Lytic lesion requiring an impending orthopedic intervention
Lack of treatment with a bisphosphonate or denosumab
Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitazone)
Active treatment with an oral or IV glucocortocoid for ≥4 weeks at a daily dose equivalent to or greater than 7.5 mg of oral prednisone
Fasting β-CTX of >1000 pg/mL
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Colin Weekes, MD, PhD,

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

Patients

Caregivers

Clinical Trial Record