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A Study of Nivolumab +/- Nab-paclitaxel in Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02967133
Recruitment Status : Active, not recruiting
First Posted : November 18, 2016
Last Update Posted : July 30, 2019
Sponsor:
Collaborators:
Celgene Corporation
Bristol-Myers Squibb
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Brief Summary:
The optimal prioritization of second-line chemotherapy and immune therapy based on demographic or biomarker data is an area of ongoing investigation. The hypothesis of this study is that there may be an additive or synergistic antitumor effect of combined chemotherapy and nivolumab in the second-line treatment of NSCLC as an important concept to test in a clinical trial. Previously treated NSCLC remains a setting of unmet clinical need despite recent clinical research progress. Early progression for a subset of NSCLC patients receiving nivolumab is a specific area of clinical need.

Condition or disease Intervention/treatment Phase
Non-Small-Cell Lung Cancer Metastatic Non-Small Cell Carcinoma of Lung, TNM Stage 4 Nonsmall Cell Lung Cancer Non Small Cell Lung Cancer Recurrent Drug: Nivolumab Drug: nab-paclitaxel Phase 2

Detailed Description:
Nab-paclitaxel will be added to standard nivolumab therapy in previously treated advanced stage non-small cell lung cancer to help prevent early progression and to improve progression free survival. The primary endpoint will be to determine if the addition of nab-paclitaxel to nivolumab improves progression free survival compared to nivolumab alone. Retrospective studies will be conducted to analyze blood based immune biomarkers, and tumor biomarkers to better understand the effect that nivolumab combined with chemotherapy has on the immune system in NSCLC. Patients with advanced stage non-small cell lung cancer who have progression of cancer after receiving platinum doublet chemotherapy will be randomized to receive nivolumab with or without nab-paclitaxel. Patients on both arms will receive a maximum of one year of therapy with the option to retreat at progression.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab With or Without Nab-Paclitaxel in Previously Treated, Advanced Stage, Non-small Cell Lung Cancer: A Randomized Phase II Study
Study Start Date : December 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A
Nivolumab q 14 days until disease progression/toxicity
Drug: Nivolumab

Arm A: Nivolumab 240 mg via intravenous infusion (IV) over 30 minutes day 1 of each 14 day cycle until disease progression or not tolerated.

Arm B: Nivolumab 360 mg via intravenous infusion (IV) over 30 minutes day 1 of every 21 day treatment cycle until progression or not tolerated.

Other Name: Opdivo

Active Comparator: Arm B

Nivolumab every 21 days until disease progression

Nab-paclitaxel every 21 days

Drug: Nivolumab

Arm A: Nivolumab 240 mg via intravenous infusion (IV) over 30 minutes day 1 of each 14 day cycle until disease progression or not tolerated.

Arm B: Nivolumab 360 mg via intravenous infusion (IV) over 30 minutes day 1 of every 21 day treatment cycle until progression or not tolerated.

Other Name: Opdivo

Drug: nab-paclitaxel
Patients in arm B receive nab-paclitaxel at a dose of 100 mg/m2 over intravenous infusion on Days 1 and 8 of each 21 day cycle.
Other Name: abraxane




Primary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: The primary endpoint will be defined as the time from the date of randomization to the date of the earliest radiographic disease progression or death. Randomization, treatment and safety follow up is defined as 30 months ]
    This study will compare the progression-free survival of patients with advanced stage non-small cell lung cancer whose cancer has progressed after standard first-line platinum based doublet chemotherapy is improved with nivolumab plus nab-paclitaxel compared to nivolumab alone.



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Histologically or cytologically confirmed, Stage IV non-small cell lung cancer (per the Union Internationale contre le Cancer/American Join Committee on Cancer staging system, 7th edition) or recurrent incurable non-small cell lung cancer that has progressed after first-line chemotherapy.
  2. Prior Therapy: Platinum doublet chemotherapy for current diagnosis of advanced lung cancer. Only one prior line of chemotherapy for advanced lung cancer allowed. Adjuvant chemotherapy, neoadjuvant chemotherapy, or chemoradiotherapy given for early stage lung cancer at least 6 months prior to diagnosis of recurrent/metastatic disease is not counted as a line of therapy for advanced lung cancer. Patients who received platinum doublet therapy with or without radiotherapy as part of treatment for early stage non-small cell lung cancer less than 6 months after developing stage 4 or recurrent incurable disease will be considered study eligible by the criterion of having received one line of chemotherapy for non-small cell lung cancer.
  3. EGFR, ALK and ROS biomarker positive tumors are eligible as long as the patient has received at least one standard oral, molecular inhibitor therapy in addition to standard platinum doublet chemotherapy. More than one molecular inhibitor is allowed such as a first generation EGFR inhibitor followed by a next generation EGFR inhibitor when T790 mutation develops. Prior molecular therapy for biomarker positive tumors such as (but not limited to) MET, RET and BRAF allowed but not required.
  4. Prior chemotherapy must have been completed 21 days prior to initiation of protocol therapy and all toxicities must < grade 2.
  5. Patients must have < Grade 2 or pre-existing neuropathy (per CTCAE).
  6. Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy.
  7. All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥10mm with spiral CT scan.
  8. ECOG Performance Status: 0-1
  9. Second malignancy: No "currently active" second malignancy other than non-melanoma skin cancers.
  10. Brain metastases: brain metastases must have been treated at least 2 weeks prior to enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be receiving a supra-physiologic dose of steroids (> 10 mg prednisone daily or equivalent).
  11. Non-pregnant and non-nursing. The effect of nab-paclitaxel and nivolumab on the fetus is unknown.
  12. Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses > 1 year.
  13. Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
  14. Age ≥18 years.
  15. Required Initial Laboratory Values:

    Leukocytes ≥2000/ µl Hemoglobin >9.0 g/dL Platelets ≥100,000/ µl ANC ≥1,500/mcL

    Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):

    Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL

    Male CrCl = (140 - age in years) x weight in kg x 1.00

    Total Bilirubin <1.5 mg/dl (except for subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dl) SGOT (AST) <2.5 x ULN ALP <2.5 x ULN in absence of liver metastases (<5 x ULN if liver metastases present PTT <1.5 x ULN

  16. An archival tumor sample from either a prior core needle biopsy or surgical specimen must be available to be submitted for correlative studies as an eligibility requirement prior to registration. The sample must be shipped within 6 weeks of enrollment. Participants without an available archival tumor sample are considered ineligible.

Exclusion Criteria:

  1. Prior nab-paclitaxel chemotherapy excluded.
  2. Prior immune therapy for NSCLC excluded. Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
  3. Patients will be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  4. Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence or active autoimmune disease.
  5. Patients should be excluded if they test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
  6. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  7. Allergies and Adverse Drug Reaction: History of allergy to study drug components

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): NCT02967133


Locations
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United States, Kentucky
St. Elizabeth's Healthcare
Edgewood, Kentucky, United States, 41017
United States, Minnesota
Metro Minnesota community oncology research consortium
Saint Louis Park, Minnesota, United States, 55416
United States, Missouri
Missouri Baptist Medical Center
Saint Louis, Missouri, United States, 63131
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
Sponsors and Collaborators
Alliance Foundation Trials, LLC.
Celgene Corporation
Bristol-Myers Squibb
Investigators
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Principal Investigator: Monica Bertagnolli, MD Alliance Foundation Trials, LLC.
Study Chair: Neal Ready, MD, PhD Alliance Foundation Trials, LLC.
Additional Information:
Publications:
Camidge R. et al. ORAL02.05 Safety and Efficacy of First-Line Nivolumab (NIVO; Anti-Programmed Death-1 [PD-1]) and Ipilimumab in Non-Small Cell Lung Cancer (NSCLC) World Lung Cancer Meeting, Denver, CO September 2015.
Adams S, et al. OT1-01-06 A phase III randomized trial of atezolizumab in combination with nab-paclitaxel as first line therapy for patients with metastatic triple-negative breast cancer (mTNBC) San Antonio Breast Cancer Meeting, San Antonio, TX December 2015.
Kaplan, E.L., Meier, P., Nonparametric estimation from incomplete observations. J Am Stat Assoc, 1958. 53(282): p. 457-481.
Cox, D.R. Regression models and life-tables. J R Stat Soc 1972 34: p.187-220.
Fine, J., Gray R., A proportional hazards model for the sub distribution of a competing risk. J Am Stat Assoc, 1999. 94: p. 496-509.

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Responsible Party: Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier: NCT02967133    
Other Study ID Numbers: AFT-31
First Posted: November 18, 2016    Key Record Dates
Last Update Posted: July 30, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Anonymized (de-identified) data generated from biospecimens used for future correlative research, including somatic and constitutional (germline) genomic data, may be shared with other researchers or deposited in a publicly accessible or controlled-access data repositories. Correlative study results and data will never be returned to individual patients.
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Nivolumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological