Safety Study of Nivolumab With Nab-Paclitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-Paclitaxel / Carboplatin in Stage IIIB/IV Non-Small Cell Lung Cancer or Nab-Paclitaxel in Recurrent Metastatic Breast Cancer
A Phase 1, Open-label, Multicenter, Safety Study of Nivolumab (Bms-936558) in Combination With Nab-pacitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-paclitaxel/Carboplatin in Stage Iiib/iv Non-small Cell Lung Cancer or Nab-paclitaxel in Metastastic Breast Cancer
1 other identifier
interventional
114
1 country
15
Brief Summary
The purpose of this study is to assess safety of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, Non Small Cell Lung Cancer (NSCLC) and Metastatic Breast Cancer (mBC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2015
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 3, 2014
CompletedFirst Posted
Study publicly available on registry
December 5, 2014
CompletedStudy Start
First participant enrolled
January 12, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 12, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 12, 2018
CompletedMay 31, 2019
May 1, 2019
3.7 years
December 3, 2014
May 29, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Evaluate Dose Limiting Toxicity (DLT) of each combination regimen
The number of subjects with dose limiting toxicity in each treatment arm in Part 1.
24 months
Evaluate the safety of the nab-paclitaxel/nivolumab combination regimens
The percentage of subjects with Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) or treatment discontinuation due to a TEAE during the study
44 months
Grade 3 or 4 TEAE
The percentage of subjects with Grade 3 or 4 TEAEs or treatment discontinuation due to a TEAE during the study.
44 months
Secondary Outcomes (6)
Treatment Emergent Adverse Events
44 months
Progression-free survival
44 months
Overall Survival
44 months
Disease Control Rate
44 Months
Overall Response Rate
44 Months
- +1 more secondary outcomes
Study Arms (6)
nab-Paclitaxel and Nivolumab in Pancreatic Cancer
EXPERIMENTALnab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28 day cycle.
nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer
EXPERIMENTALnab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, gemcitabine 1000 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28-day cycle.
nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC
EXPERIMENTALnab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 (Cycles 1 to 4 only) of each 21 day cycle; nivolumab on Day 15 of each 21 day cycle starting in Cycle 1.
nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC
EXPERIMENTALnab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 (Cycles 1 to 4 only) of each 21 day cycle; nivolumab on Day 15 of each 21 day cycle starting in Cycle 3.
nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC
EXPERIMENTALnab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 28 day cycle, plus nivolumab on Days 1 and 15 starting in Cycle 3.
nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC
EXPERIMENTALnab-paclitaxel 260 mg/m2 on Days 1 of each 21 day cycle, plus nivolumab on Days 15 starting in Cycle 3.
Interventions
Eligibility Criteria
You may qualify if:
- Subject is male or female, ≥ 18 years old at the time of signing the informed consent form (ICF).
- Subject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:
- Pancreatic Cancer
- \- Subject has a definitive histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas. Subjects with islet cell neoplasms are excluded.
- nab-Paclitaxel and Nivolumab: Subjects must have received 1 prior systemic chemotherapy regimen for locally advanced or metastatic disease.
- nab-Paclitaxel + Nivolumab and nab-paclitaxel, Gemcitabine and Nivolumab: Subjects must have received no previous systemic chemotherapy or investigational therapy for the treatment of pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy, with the exception of prior treatment administered as a radiosensitizer concomitant with radiotherapy in the adjuvant setting. In this case, ≥ 6 months must have elapsed since completion of the last dose and no lingering toxicities may be present. Initial diagnosis of metastatic disease must have occurred ≤ 6 weeks prior to randomization in the study.
- Non-small Cell Lung Cancer (NSCLC):
- \- Subject has definitive histologically or cytologically confirmed Stage IIIB or IV NSCLC.
- Subjects must have received no previous chemotherapy or investigational therapy for the treatment of metastatic disease. Adjuvant, neo-adjuvant chemotherapy or chemoradiotherapy is permitted providing cytotoxic chemotherapy was completed \> 12 months prior to randomization, without disease recurrence or progression during those 12 months.
- Metastatic Breast Cancer: Human Epidermal Growth Factor Receptor 2 - negative (HER2(-)) recurrent Metastatic Breast Cancer:
- Subject has a definitive histologically or cytologically confirmed diagnosis of HER2(-) metastatic breast cancer.
- Subject has received zero to one prior cytotoxic chemotherapy regimen for metastatic disease, regardless of prior targeted therapy (eg. everolimus, palbociclib or lapatinib), biologic (eg. trastuzumab) or hormonal therapy treatment (eg. aromatase inhibitors, selective estrogen receptor modulators, or estrogen receptor down-regulators).
- If subject has received solvent-based paclitaxel (TAXOL) or docetaxel as adjuvant chemotherapy, subject must not have relapsed with breast cancer within 12 months of completing said therapy.
- Suitable candidate for single agent nab-paclitaxel as assessed by the investigator.
- \. Subject has measurable disease according to RECIST 1.1. 4. Archival formalin-fixed, paraffin-embedded tumor sample collected within 90 days prior to subject consent available or subject has biopsiable metastatic lesion and is willing to undergo biopsy .
- +19 more criteria
You may not qualify if:
- Subject has a history of allergy or hypersensitivity to any study drugs or their excipients.
- Subject has had prior therapy with T-cell immune modulating antibodies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1.
- Subject has symptomatic brain metastases, spinal cord compression, or intractable back pain due to compression of destructive mass.
- Subject has active, known or suspected autoimmune disease, including systemic lupus erythematodes, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa or auto-immune hepatitis. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Subject is currently receiving or requires treatment with immunosuppressive agents or immunosuppressive doses of systemic corticosteroids (unless used to treat drug-related adverse events).Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption), and some uses of systemic corticosteroids are permitted as per Section 9.1.
- Subject has any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events ) Grade 2 at randomization/enrollment.
- Subject has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Subject has a high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year.
- Subject has unstable angina, a significant cardiac arrhythmia, or New York Heart Association Class 3 or 4 congestive heart failure.
- Subject has a history of peripheral artery disease (eg, claudication, Leo Buerger's disease).
- Subject has had major surgery, other than diagnostic surgery, within 4 weeks prior to treatment in study.
- Subject has known acute or chronic pancreatitis.
- Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ≥ NCI CTCAE Grade 2, despite medical management.
- Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- Subject has any history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS).
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (15)
UC Davis Cancer Center
Sacramento, California, 95817, United States
University of California Los Angeles
Santa Monica, California, 90404, United States
Yale Cancer Center
New Haven, Connecticut, 06510, United States
H. Lee Moffitt Cancer Center and Research Institute University of South Florida
Tampa, Florida, 33612, United States
Northwestern University-NMDTI
Chicago, Illinois, 60611, United States
Dana-Farber / Harvard Cancer Institute
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Regional Care Cancer Centers NJ
Morristown, New Jersey, 79062, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45242, United States
Ohio State Medical Center
Columbus, Ohio, 43210, United States
University of Pennslyvania
Philadelphia, Pennsylvania, 19104, United States
Seattle Cancer Center Alliance
Seattle, Washington, 98109, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Goldman JW, Waterhouse DM, George B, O'Dwyer PJ, Bhore R, Banerjee S, Lyons L, Louis CU, Ong TJ, Kelly K. Safety and Efficacy Results of a Phase I, Open-Label Study of Concurrent and Delayed Nivolumab in Combination With nab-Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer. Front Oncol. 2019 Nov 26;9:1256. doi: 10.3389/fonc.2019.01256. eCollection 2019.
PMID: 31850192DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Chrystal Louis
Celgene Corporation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 3, 2014
First Posted
December 5, 2014
Study Start
January 12, 2015
Primary Completion
September 12, 2018
Study Completion
September 12, 2018
Last Updated
May 31, 2019
Record last verified: 2019-05