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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

This study is currently recruiting participants.
Verified September 2017 by Celgene
Sponsor:
ClinicalTrials.gov Identifier:
NCT02309177
First Posted: December 5, 2014
Last Update Posted: September 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Celgene
  Purpose
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).

Condition Intervention Phase
Breast Neoplasms Pancreatic Neoplasms Drug: nab-Paclitaxel Drug: Nivolumab Drug: Gemcitabine Drug: Carboplatin Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Evaluate Dose Limiting Toxicity (DLT) of each combination regimen [ Time Frame: 24 months ]
    The number of subjects with dose limiting toxicity in each treatment arm in Part 1.

  • Evaluate the safety of the nab-paclitaxel/nivolumab combination regimens [ Time Frame: 44 months ]
    The percentage of subjects with Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) or treatment discontinuation due to a TEAE during the study

  • Grade 3 or 4 TEAE [ Time Frame: 44 months ]
    The percentage of subjects with Grade 3 or 4 TEAEs or treatment discontinuation due to a TEAE during the study.


Secondary Outcome Measures:
  • Treatment Emergent Adverse Events [ Time Frame: 44 months ]
    TEAEs leading to dose reduction, delay, interruption or treatment discontinuation

  • Progression-free survival [ Time Frame: 44 months ]
    Progression-free survival, which is defined as the time from the date of first dose of any IP to the date of disease progression or death (any cause) on or prior to the data cutoff date for analyses.

  • Overall Survival [ Time Frame: 44 months ]
    Overall survival is defined as the time between the first dose of any IP and death.

  • Disease Control Rate [ Time Frame: 44 Months ]
    Disease control rate is defined as the percent of subjects who have a radiographically assessed complete response, partial response, or stable disease as determined by the investigator according to RECIST 1.1 guidelines.

  • Overall Response Rate [ Time Frame: 44 Months ]
    Overall response rate is defined as the percent of subjects who have a radiographically assessed complete or partial response as determined by the investigator according to RECIST 1.1 guidelines.

  • Duration of Response [ Time Frame: 44 Months ]
    The duration of overall response is measured from the time measurement criteria are met, based on RECIST 1.1 guidelines, for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).


Estimated Enrollment: 138
Actual Study Start Date: January 14, 2015
Estimated Study Completion Date: October 26, 2018
Estimated Primary Completion Date: October 26, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nab-Paclitaxel and Nivolumab in Pancreatic Cancer
nab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28 day cycle.
Drug: nab-Paclitaxel
Other Name: Abraxane
Drug: Nivolumab
Other Name: BMS-936558 or MDX1106
Experimental: nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer
nab-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.
Drug: nab-Paclitaxel
Other Name: Abraxane
Drug: Nivolumab
Other Name: BMS-936558 or MDX1106
Drug: Gemcitabine
Other Name: Gemzar
Experimental: nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC
nab-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.
Drug: nab-Paclitaxel
Other Name: Abraxane
Drug: Nivolumab
Other Name: BMS-936558 or MDX1106
Drug: Carboplatin
Other Name: Paraplatin
Experimental: nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC
nab-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.
Drug: nab-Paclitaxel
Other Name: Abraxane
Drug: Nivolumab
Other Name: BMS-936558 or MDX1106
Drug: Carboplatin
Other Name: Paraplatin
Experimental: nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC
nab-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.
Drug: nab-Paclitaxel
Other Name: Abraxane
Drug: Nivolumab
Other Name: BMS-936558 or MDX1106
Experimental: nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC
nab-paclitaxel 260 mg/m2 on Days 1 of each 21 day cycle, plus nivolumab on Days 15 starting in Cycle 3.
Drug: nab-Paclitaxel
Other Name: Abraxane
Drug: Nivolumab
Other Name: BMS-936558 or MDX1106

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is male or female, ≥ 18 years old at the time of signing the informed consent form (ICF).
  2. Subject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:

    1. 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.
    2. 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.
  3. Non-small Cell Lung Cancer (NSCLC):

    - Subject has definitive histologically or cytologically confirmed Stage IIIB or IV NSCLC.

  4. 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.
  5. 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.

3. 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 .

5. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

6. Subject has no other malignancy within 5 years, except non-melanoma skin cancer, cervical intraepithelial neoplasia, or in-situ cervical cancer or incidental histological finding of prostate cancer (TNM stage of T1a or T1b); all treatments of which should have been completed 6 months prior to signing ICF.

7. Subject has the following laboratory values at screening:

- WBCs ≥ 2000/uL,

  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,
  • Hemoglobin (Hgb) ≥ 90 g/L,
  • Platelets (plt) ≥ 100 x 109/L,
  • Potassium within normal range, or correctable with supplements,
  • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 3.0 x ULN if liver tumor is present,
  • Serum total bilirubin ≤ 1.5 x ULN (except in subjects with Gilbert's who may have serum bilirubin < 3.0 x ULN),
  • Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60 mL/min,
  • Normal coagulation [prothrombin time and partial thromboplastin time within normal limits (±15%)].

    8. Subject has resting baseline oxygen saturation by pulse oximetry of ≥ 92% at rest.

    9. Females of child-bearing potential (defined as a sexually mature woman who: 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, 2) has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months) must:

    a. Agree in writing to use two forms of medical doctor-approved contraception throughout the study (without interruptions while on study treatment) and subsequently for 23 weeks5 months.

    b. Have a negative serum pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of β hCG) at screening and 24 hours prior to the start of any IP and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.

    10. Male subjects agree in writing to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 7 months following IP discontinuation, even if he has undergone a successful vasectomy.

    11. Subject or his/her legally authorized representative or guardian understands and voluntarily signs an informed consent document prior to any study related assessments/procedures are conducted (except as noted in Section 6).

    12. Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  1. Subject has a history of allergy or hypersensitivity to any study drugs or their excipients.
  2. Subject has had prior therapy with T-cell immune modulating antibodies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1.
  3. Subject has symptomatic brain metastases, spinal cord compression, or intractable back pain due to compression of destructive mass.
  4. 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.
  5. 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.
  6. Subject has any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events ) Grade 2 at randomization/enrollment.
  7. 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.
  8. Subject has a high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year.
  9. Subject has unstable angina, a significant cardiac arrhythmia, or New York Heart Association Class 3 or 4 congestive heart failure.
  10. Subject has a history of peripheral artery disease (eg, claudication, Leo Buerger's disease).
  11. Subject has had major surgery, other than diagnostic surgery, within 4 weeks prior to treatment in study.
  12. Subject has known acute or chronic pancreatitis.
  13. Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ≥ NCI CTCAE Grade 2, despite medical management.
  14. Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  15. Subject has any history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS).
  16. Subject has active hepatitis B or C. Subject with hepatitis in medical history may be eligible if infection considered cleared, ie core Ab+, surface Ab+, surface Ag- for hep B and Ab+/DNA- for hep C.
  17. Subject is pregnant or breast-feeding. Women must not breast-feed until at 5 months after completion of study participation..
  18. Subject is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug.
  19. Subject is currently using or use within 6 months of illicit drugs.
  20. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  21. Subject has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  22. Subject has any condition that confounds the ability to interpret data from the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02309177


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, Arizona
Mayo Clinic Arizona Not yet recruiting
Scottsdale, Arizona, United States, 85259
United States, California
UC Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
University of California Los Angeles Recruiting
Santa Monica, California, United States, 90404
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute University of South Florida Recruiting
Tampa, Florida, United States, 33612
United States, Illinois
Northwestern University-NMDTI Recruiting
Chicago, Illinois, United States, 60611
United States, Massachusetts
Dana-Farber / Harvard Cancer Institute Recruiting
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Regional Care Cancer Centers NJ Completed
Morristown, New Jersey, United States, 79062
United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
United States, Ohio
Oncology Hematology Care, Inc. Recruiting
Cincinnati, Ohio, United States, 45242
Ohio State Medical Center Recruiting
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Seattle Cancer Center Alliance Recruiting
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Celgene
Investigators
Study Director: Chrystal Louis Celgene Corporation
  More Information

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02309177     History of Changes
Other Study ID Numbers: ABI-007-ST-001
First Submitted: December 3, 2014
First Posted: December 5, 2014
Last Update Posted: September 4, 2017
Last Verified: September 2017

Keywords provided by Celgene:
Pancreatic Cancer
Breast Cancer
Metastatic Breast Cancer
nab-Paclitaxel
Gemcitabine
Carboplatin
Non-Small Cell Lung Cancer
Lung Cancer
mBC
NSCLC
Triple-negative Breast Cancer
Hormone Receptor Positive
ER+
PR+
TNBC
Nivolumab
PD-1
Check-point Inhibitor/s
Immune Check-point Inhibitor/s
Anti-PD-1
BMS-936558

Additional relevant MeSH terms:
Breast Neoplasms
Lung Neoplasms
Neoplasms
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Nivolumab
Albumin-Bound Paclitaxel
Carboplatin
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators