Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer
Primary Purpose
Pancreatic Cancer, Stage IV Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
OMP-54F28, Nab-Paclitaxel and Gemcitabine
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring Pancreatic Cancer, Stage IV Pancreatic Cancer
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- USC/Norris Comprehensive Cancer Center
- University of Colorado Hospital Anschutz Cancer Pavilion
- Indiana University Simon Cancer Center
- Fox Chase Cancer Center
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Drug: OMP-54F28, Nab-Paclitaxel and Gemcitabine
Arm Description
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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
Full Information
NCT ID
NCT02050178
First Posted
January 28, 2014
Last Updated
September 7, 2020
Sponsor
OncoMed Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02050178
Brief Title
Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer
Official Title
A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
November 2013 (undefined)
Primary Completion Date
June 15, 2017 (Actual)
Study Completion Date
June 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OncoMed Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Stage IV Pancreatic Cancer
Keywords
Pancreatic Cancer, Stage IV Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Drug: OMP-54F28, Nab-Paclitaxel and Gemcitabine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
OMP-54F28, Nab-Paclitaxel and Gemcitabine
Primary Outcome Measure Information:
Title
Safety and tolerability of OMP-54F28 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated Stage IV pancreatic cancer
Description
The maximum tolerated dose (MTD) will be determined in patients treated with gemcitabine in combination with weekly nab-paclitaxel (from Day 0 - 28)
Time Frame
Subjects will be treated and observed for DLT through the end of the first cycle (from Day 0 - 28)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of OMP-54F28 when administered in combination with nabpaclitaxel and gemcitabine to patients with previously untreated Stage IV pancreatic cancer
Description
Apparent half life, AUC, clearance, volume of distribution
Time Frame
Plasma sample for Pharmacokinetics (PK) analysis to be obtained prior to the gemcitabine infusion and before nabpaclitaxel infusion from Day 0 to treatment termination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Colin Weekes, MD, PhD
Official's Role
Principal Investigator
Facility Information:
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of Colorado Hospital Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Indiana University Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer
We'll reach out to this number within 24 hrs