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Docetaxel Plus Nivolumab or Docetaxel Alone in Patients With Advanced NSCLC Previously Treated With a PD-1 or PD-L1 Inhibitor

This study is currently recruiting participants.
Verified August 2017 by Greg Durm, MD, Hoosier Cancer Research Network
Sponsor:
ClinicalTrials.gov Identifier:
NCT03041181
First Posted: February 2, 2017
Last Update Posted: September 1, 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.
Collaborators:
Hoosier Cancer Research Network
Bristol-Myers Squibb
Information provided by (Responsible Party):
Greg Durm, MD, Hoosier Cancer Research Network
  Purpose

This is a randomized phase II study assessing the activity of docetaxel combined with nivolumab compared to docetaxel alone in metastatic or recurrent squamous or non-squamous non-small cell lung cancer (NSCLC) subjects who recently progressed on a PD-1 or PD-L1 inhibitor.

Upon registration, subjects will be randomized in a 1:1 ratio to either treatment with docetaxel alone or docetaxel in combination with nivolumab. Randomization is un-blinded and open-label; therefore there will be no placebo treatment for subjects randomized to docetaxel monotherapy.


Condition Intervention Phase
Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Adenocarcinoma of the Lung Lung Cancer Drug: Docetaxel Drug: Nivolumab Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
Open-Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Docetaxel Plus Nivolumab or Docetaxel Alone in Patients With Advanced Squamous or Non-squamous NSCLC and Previous Clinical Benefit on Treatment With a PD-1 or PD-L1 Inhibitor: Hoosier Cancer Research Network LUN15-233

Resource links provided by NLM:


Further study details as provided by Greg Durm, MD, Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Progression free survival (PFS), as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. [ Time Frame: From date of randomization until the criteria for disease progression is met or death as a result of any cause, assessed up to 24 months ]
    Compare PFS rates for subjects on each treatment arm, per RECIST 1.1. Subjects who have not progressed will be right-censored at the date of the last disease evaluation.


Secondary Outcome Measures:
  • Number of subjects with adverse events as a measure of safety and tolerability - Assess toxicity in both arms and compare grade 3 & 4 toxicities in each arm [ Time Frame: Treatment-related toxicities will be assessed D1 of each 21-day cycle, for up to 24 months ]
    Toxicity assessed per NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.

  • Response rates (RR) for subjects on each treatment arm, as defined by RECIST 1.1 and immune-related response criteria (irRECIST) [ Time Frame: Every 6 weeks beginning with C3D1 and every odd numbered cycle thereafter, assessed for up to 24 months ]
    Proportion of subjects on each arm with complete response or partial response, per RECIST 1.1 and irRECIST

  • Clinical benefit for subjects on each treatment arm, as defined by RECIST 1.1 and irRECIST [ Time Frame: From D1 of treatment until documented disease progression/recurrence, assessed for up to 24 months ]
    Proportion of subjects on each arm with complete response, partial response or stable disease for at least 3 months, per RECIST 1.1 and irRECIST

  • Progression free survival (PFS), as defined by irRECIST [ Time Frame: From date of randomization until the criteria for disease progression is met or death as a result of any cause, assessed up to 24 months ]
    Compare PFS rates for subjects on each treatment arm, per irRECIST


Estimated Enrollment: 58
Actual Study Start Date: January 27, 2017
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Investigational Arm A
Docetaxel 75 mg/m^2 IV plus nivolumab 360 mg IV every 21 days (21 days = 1 cycle)
Drug: Docetaxel
Docetaxel 75 mg/m^2 IV every 21 days (21 days = 1 cycle)
Other Name: Taxotere
Drug: Nivolumab
Nivolumab 360 mg IV every 21 days (21 days = 1 cycle)
Other Names:
  • BMS-936558-01
  • Opdivo
Experimental: Investigational Arm B
Docetaxel monotherapy 75 mg/m^2 every 21 days (21 days = 1 cycle)
Drug: Docetaxel
Docetaxel 75 mg/m^2 IV every 21 days (21 days = 1 cycle)
Other Name: Taxotere

Detailed Description:

OUTLINE: This is a multi-center study.

INVESTIGATIONAL TREATMENT:

Eligible subjects will be randomized in 1:1 ratio to receive treatment with either:

Arm A: docetaxel 75 mg/meters squared (mg/m^2) plus nivolumab 360 mg IV every 21 days

Arm B: docetaxel alone 75 mg/m^2 every 21 days

For both treatment arms, 21 days equals 1 cycle of therapy and subjects will be eligible to continue treatment until progressive disease by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) or unacceptable toxicity.

The following screening labs to demonstrate adequate organ function must be performed within 30 days prior to registration:

Hematological:

  • White Blood Cell (WBC) ≥ 2 k/mm^3
  • Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Platelet >100k

Renal:

  • Calculated creatinine clearance ≥ 40 cc/min
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)

Hepatic:

  • Bilirubin 1.5 ≤ upper limit of normal (ULN)^2
  • Aspartate aminotransferase (AST) ≤ 1.5 × ULN
  • Alanine aminotransferase (ALT) ≤ 1.5 × ULN

Coagulation:

  • International Normalized Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN

(Note: use of vitamin K antagonist is not allowed)

  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:

Subject must meet all of the following applicable inclusion criteria to participate in this study:

  • Written informed consent and the American Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 30 days prior to registration.
  • Histological or cytological confirmed non-squamous non-small cell lung cancer.
  • Measurable disease according to RECIST 1.1 within 30 days prior to registration.
  • A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
  • Subjects must have had clinical benefit while on a PD-1 or PD-L1 inhibitor defined as at least a 3 month progression free survival (PFS), and now have progression.
  • Most recent PD-1 or PD-L1 inhibitor infusion must be completed at least 6 weeks of randomization. The subject must have recovered from all reversible acute toxic effects (other than alopecia) to ≤ Grade 1 or baseline.
  • Patients must have received prior treatment with chemotherapy. Chemotherapy may have previously been given with a PD-1 or PD-L1 inhibitor.
  • MANDATORY archival tumor tissue (prior to treatment with a PD-1 or PD-L1 inhibitor) must be identified during screening and confirmation of acquisition should occur prior to registration. Archival tissue should not be shipped until registration of patient to study. Unavailability of tissue will render the subject ineligible for study. Sample requirement is FFPE block + 2 H&E stained slides or 17 unstained slides + 1 H&E stained slide.
  • MANDATORY biopsy after registration and prior to C1D1 treatment: Primary tumor or a metastatic lesion must be amenable to biopsy after registration and prior to C1D1 treatment for PD-L1 status and other correlative studies. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is allowed as long as there is sufficient cellularity. Sample requirement is FFPE block + 2 H&E stained slides or 17 unstained slides + 1 H&E stained slide.
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days prior to registration. These women must also have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab then every 6 weeks thereafter. NOTE: Women are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is post-menopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
  • Women of childbearing potential must be willing to abstain from heterosexual activity or use an effective method of contraception from the time of informed consent until 5 months after treatment discontinuation. Women cannot breast feed from the time of informed consent to 5 months after last dose of study treatment.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

Subjects meeting any of the criteria below may not participate in the study:

  • Prior treatment with Docetaxel.
  • Previous autoimmune complication from PD-1 or PD-L1 requiring discontinuation of therapy or treatment with steroids (ongoing treatment with more than 10 mg of prednisone or steroid equivalent daily, excluding inhaled or topical steroids).
  • Previous discontinuation from PD-1 or PD-L1 due to an adverse event.
  • Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
  • Active central nervous system (CNS) metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
  • Treatment with any investigational drug within 30 days prior to registration.
  • Subjects whose tumors express EGFR mutations on exons 19 and 21, ALK rearrangement, or ROS1 rearrangement who still have other FDA approved targeted agents available for treatment.
  • Subjects with an active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids/immunosuppressive medications EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger. (Subjects with vitiligo, autoimmune thyroiditis, or type I diabetes mellitus are permitted to enroll.)
  • As there is potential for hepatic toxicity with Nivolumab, drugs with a predisposition to hepatoxicity should be used with caution in subjects treated with Nivolumab-containing regimen.
  • Subjects should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
  • Subjects should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of allergy to study drug components.
  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): NCT03041181


Contacts
Contact: Donna Sullivan 317.634.5842 ext 40 dsullivan@hoosiercancer.org
Contact: Greg Durm, M.D. 317.656.4260 gdurm@iu.edu

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Greg Durm, M.D.       gdurm@iu.edu   
Contact: Maggie Uhrich    317-274-4505    muhrich@iu.edu   
IU Health Central Indiana Cancer Center Recruiting
Indianapolis, Indiana, United States, 46219
Contact: Melody Sands    317-678-2700    MSands1@iuhealth.org   
Principal Investigator: Andrew Greenspan, MD         
Community Regional Cancer Care Recruiting
Indianapolis, Indiana, United States, 46256
Contact: Kelly Verel    317-497-2836    KVerel@ecommunity.com   
Principal Investigator: Radhika Walling, MD         
IU Health Ball Memorial Hospital Cancer Center Recruiting
Muncie, Indiana, United States, 47303
Contact: Stacey Cadogan    765-281-2030    scadogan@iuhealth.org   
Principal Investigator: William Fisher, MD         
United States, Texas
University of Texas Medical Branch at Galveston Recruiting
Galveston, Texas, United States, 77555
Contact: Renee Brown    409-772-9583    renbrown@utmb.edu   
Principal Investigator: Maurice Willis, MD         
Sponsors and Collaborators
Greg Durm, MD
Hoosier Cancer Research Network
Bristol-Myers Squibb
Investigators
Study Chair: Greg Durm, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
Responsible Party: Greg Durm, MD, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT03041181     History of Changes
Other Study ID Numbers: HCRN LUN15-233
First Submitted: January 31, 2017
First Posted: February 2, 2017
Last Update Posted: September 1, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Greg Durm, MD, Hoosier Cancer Research Network:
Nivolumab
BMS-936558-01
Anti-PD-1 Antibody
Docetaxel

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Docetaxel
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs