Clinical Trials /

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

NCT02309177

Description:

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).

Related Conditions:
  • Breast Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Safety Study of Nivolumab With <span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span> Plus or Minus <span class="go-doc-concept go-doc-intervention">Gemcitabine</span> in <span class="go-doc-concept go-doc-disease">Pancreatic Cancer</span>, <span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span> / <span class="go-doc-concept go-doc-intervention">Carboplatin</span> in Stage IIIB/IV Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> or <span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span> in Recurrent Metastatic <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: 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
  • Official Title: A Phase 1, Open-Label, Multicenter, Safety Study of Nivolumab (BMS-936558) in Combination 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
  • Clinical Trial IDs

    NCT ID: NCT02309177

    ORG ID: ABI-007-ST-001

    Trial Conditions

    Breast Neoplasms

    Pancreatic Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    nab-Paclitaxel Abraxane nab-Paclitaxel and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC, nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC, nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC, nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC
    Nivolumab BMS-936558 or MDX1106 nab-Paclitaxel and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer, nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC, nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC, nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC, nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC
    Gemcitabine Gemzar nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer
    Carboplatin Paraplatin nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC, nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC

    Trial 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).

    Detailed Description

    This will be a phase 1, open-label, multicenter, safety study of nab-paclitaxel based
    chemotherapy regimens administered prior to and/or in combination with nivolumab in
    Pancreatic Cancer, NSCLC and mBC. This is a six arm study assessing two treatment arms per
    tumor-type/indication:

    - Adenocarcinoma of the pancreas with 1 prior systemic chemotherapy (Arm A, Part 1 only);
    and subsequently no prior chemotherapy, surgery or radiation therapy for locally
    advanced or metastatic disease (Arm A, Part 2 and Arm B):

    - Panc Ca Arm A: nab-paclitaxel with nivolumab starting at Cycle 1.

    - Panc Ca Arm B: nab-paclitaxel/gemcitabine with nivolumab starting at Cycle 1.

    - Stage IIIB or IV NSCLC with no prior chemotherapy for metastatic disease and who are
    not candidates for curative surgery or radiation:

    - NSCLC Arm C: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle
    1 and continuing as monotherapy starting at Cycle 5.

    - NSCLC Arm D: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle
    3 and continuing as monotherapy starting at Cycle 5

    - HER2-negative recurrent metastatic breast cancer after one prior regimen for mBC,
    including an anthracycline unless clinically contraindicated:

    - mBC Arm E: weekly nab-paclitaxel with nivolumab starting at Cycle 3.

    - mBC Arm F: q3weekly nab-paclitaxel with nivolumab starting at Cycle 3.
    Enrollment in each treatment arm will be conducted in two sequential parts to
    allow for the evaluation of the DLT in Part 1 prior to expanding the treatment arm
    in Part 2.

    Part 1:

    Part 1 will assess the Dose Limiting Toxicity (DLT) of the nivolumab dose in combination
    with nab-paclitaxel regimens in each treatment arm.

    Subjects who meet the entry criteria will be assigned to the respective treatment arm based
    on tumor type and indication as outlined above. Panc Ca Arms A and B, as well as NSCLC Arms
    C and D, will enroll sequentially in Part 1. The safety of nivolumab in combination with
    nabpaclitaxel, without gemcitabine, will first be assessed in Arm A in subjects with one
    prior systemic chemotherapy regimen for locally advanced or metastatic disease. Panc Ca Arm
    B may begin enrolling subjects in Part 1, if Panc Ca Arm A is deemed safe, based on DLT
    criteria. Similarly, NSCLC Arm D will begin to enroll in Part 1 after NSCLC Arm C is deemed
    safe to expand in Part 2. However, Arm D may be initiated, even if Arm C is not to proceed
    for Part 2, if the totality of data from Arm C and emerging data from this and other studies
    in NSCLC with nivolumab in combination with platinum chemotherapy doublets support the
    decision. Unlike the Panc Ca and NSCLC arms, the two mBC arms (Arms E and F) will be
    initiated simultaneously. Subjects will be assigned randomly between treatment arms of a
    tumor type/indication whenever both treatment arms are enrolling. An IRT system will be used
    to ensure the central random allocation of subjects.

    Part 2:

    Treatment arms deemed safe within each tumor-type/indication may be expanded using the RP2D
    with an additional approximately 14 subjects (to attain a total of 20 nivolumab-treated
    subjects) to further assess safety and tolerability, as well as explore anti-tumor activity
    of the proposed regimens. Since the primary population for the pancreas arms is in subjects
    with no prior chemotherapy, surgery or radiation therapy, enrollment in Part 2 for Panc Ca
    Arm A will continue until 20 such subjects have been treated with at least one dose of
    nivolumab. Additionally, in Parts 1 and 2 overall, each mBC Arm (E and F) will enroll a
    minimum of 9 subjects with triple- negative breast cancer (TNBC), treated at the RP2D.

    For both Part 1 and 2, subjects may continue to receive their assigned treatment regimen
    until Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined progression or until
    unacceptable toxicity. However, the chemotherapy doublet will only be given for 4 cycles in
    the NSCLC arms; thereafter, nivolumab will be given as monotherapy.

    Trial Arms

    Name Type Description Interventions
    nab-Paclitaxel and Nivolumab in Pancreatic Cancer Experimental nab-paclitaxel 125 mg/m2 on Days 1, 8 and 15, and nivolumab on Days 1 and 15 of each 28 day cycle. nab-Paclitaxel, Nivolumab
    nab-Paclitaxel, Gemcitabine and Nivolumab in Pancreatic Cancer Experimental 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. nab-Paclitaxel, Nivolumab, Gemcitabine
    nab-Paclitaxel, carboplatin and nivolumab Cycle 1 in NSCLC Experimental 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. nab-Paclitaxel, Nivolumab, Carboplatin
    nab-Paclitaxel, carboplatin and nivolumab Cycle 3 in NSCLC Experimental 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. nab-Paclitaxel, Nivolumab, Carboplatin
    nab-Paclitaxel 100 mg/m2 and Nivolumab in MBC Experimental 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. nab-Paclitaxel, Nivolumab
    nab-Paclitaxel 260 mg/m2 and Nivolumab in MBC Experimental nab-paclitaxel 260 mg/m2 on Days 1 of each 21 day cycle, plus nivolumab on Days 15 starting in Cycle 3. nab-Paclitaxel, Nivolumab

    Eligibility 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.

    - nab-Paclitaxel + Nivolumab and nab-paclitaxel , Gemcitabine and Nivolumab
    : Subjects must have received no previous radiotherapy, surgery,
    chemotherapy or investigational therapy for the treatment of locally
    advanced or metastatic disease. Subjects having received cytotoxic doses of
    gemcitabine or any other chemotherapy in the adjuvant setting are not
    eligible for inclusion. Prior treatment with 5-FU or gemcitabine
    administered as a radiation sensitizer in the adjuvant setting is allowed,
    but 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.

    2. 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 chemotherapy is
    permitted providing cytotoxic chemotherapy was completed > 12 months prior
    to randomization, without disease recurrence or progression during those 12
    months.

    3. Recurrent 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 one prior cytotoxic chemotherapy regimen for
    metastatic disease, including an anthracycline unless clinically
    contraindicated. (Clinically contraindicated is defined as unless: [a.]
    anthracycline treatment was not indicated or was not the best treatment
    option for the subject in the opinion of the treating physician; and [b.]
    anthracycline treatment remains not indicated or, in the opinion of the
    treating physician, is not the best treatment option for the subject's
    metastatic disease.)

    - 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.

    3. 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 .

    4. Subject has no other malignancy within 5 years, except non-melanoma skin cancer,
    cervical intraepithelial neoplasia, or in-situ cervical cancer.

    5. 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%)].

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

    7. 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:

    1. Agree in writing to use, and be able to comply with, highly effective
    contraception (failure rate less than 1% per year) based on Appendix B without
    interruption while on study treatment and for 23 weeks after discontinuation;
    and

    2. Have a negative serum pregnancy test result (minimum sensitivity 25 IU/L or
    equivalent units of -hCG (Beta Subunit of Human Chorionic Gonadotropin)) 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.

    3. Women must not be breastfeeding. (Females should not be breastfeeding while
    receiving nivolumab and up to 18 weeks from the last dose of nivolumab).

    8. 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 31 weeks following IP discontinuation, even if he has
    undergone a successful vasectomy.

    9. 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).

    10. 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 symptomatic brain metastases, spinal cord compression, or intractable
    back pain due to compression of destructive mass.

    3. 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.

    4. 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.

    5. Subject has any peripheral neuropathy NCI CTCAE (National Cancer Institute Common
    Terminology Criteria for Adverse Events ) Grade 2 at randomization/enrollment.

    6. 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.

    7. Subject has a high cardiovascular risk, including, but not limited to, recent
    coronary stenting or myocardial infarction in the past year.

    8. Subject has unstable angina, a significant cardiac arrhythmia, or New York Heart
    Association Class 3 or 4 congestive heart failure.

    9. Subject has a history of peripheral artery disease (eg, claudication, Leo Buerger's
    disease).

    10. Subject has had major surgery, other than diagnostic surgery, within 4 weeks prior to
    treatment in study.

    11. Subject has known acute or chronic pancreatitis.

    12. Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction
    NCI CTCAE Grade 2, despite medical management.

    13. Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring
    systemic therapy.

    14. Subject has any history of testing positive for Human Immunodeficiency Virus (HIV) or
    known acquired immunodeficiency disorder (AIDS).

    15. Subject has historical or active infection with hepatitis B, or hepatitis C.

    16. Subject is pregnant or breast-feeding.

    17. 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.

    18. Subject is currently using or use within 6 months of illicit drugs.

    19. Subject has any significant medical condition, laboratory abnormality, or psychiatric
    illness that would prevent the subject from participating in the study.

    20. 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.

    21. Subject has any condition that confounds the ability to interpret data from the
    study.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Evaluate Dose Limiting Toxicity (DLT) of each combination regimen

    Evaluate the safety of the nab-paclitaxel/nivolumab combination regimens

    Grade 3 or 4 TEAE

    Secondary Outcome Measures

    Treatment Emergent Adverse Events

    Progression-free survival

    Overall Survival

    Disease Control Rate

    Overall Response Rate

    Duration of Response

    Trial Keywords

    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