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Radiation and Chemotherapy With Ipilimumab Followed by Nivolumab for Patients With Stage III Unresectable Non-Small Cell Lung Cancer (NSCLC)

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.
 
ClinicalTrials.gov Identifier: NCT03663166
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE September 6, 2018
First Posted Date  ICMJE September 10, 2018
Last Update Posted Date November 22, 2019
Actual Study Start Date  ICMJE November 20, 2018
Estimated Primary Completion Date March 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • Unacceptable toxicity status at the end of 8-week safety observation period [ Time Frame: At 8 weeks of treatment ]
    Unacceptable toxicity defined as:
    • Any grade 4 immune related adverse event (irAE)
    • Any grade 3 irAE, excluding pneumonitis, that does not downgrade to grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to ≤ grade 1 or baseline within 14 days
    • Liver transaminase elevation > 8 × ULN or total bilirubin > 5 × ULN,
    • Any ≥ grade 3 non-irAE, with some exclusions.
  • 12 month Progression Free Survival (PFS) status [ Time Frame: 12 months post treatment ]
    PFS is defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration (as defined in Outcome 1) or death due to any cause. Patients last known to be alive without report of progression are censored at date of last disease assessment. For patients with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan (as defined by the disease assessment schedule) will be used as the date of progression.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • 12 month distant metastasis free survival (DMFS) [ Time Frame: 12 months post treatment ]
    DMFS is defined as the duration from date of registration to date of first documentation of distant metastatic progression beyond the primary tumor site as well as regional lymph nodes assessed by local investigator or symptomatic deterioration (as defined in Outcome 1) or death due to any cause. Patients last known to be alive without report of distant metastatic progression are censored at date of last disease assessment.
  • Objective Response Rate (ORR) at 6 months [ Time Frame: 6 months ]
    ORR is defined as the proportion of all treated subjects whose best overall response is either a complete response or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Best Objective Response (BOR) will also be reported Complete Response (CR) or Partial Response (PR) determinations included in the assessment must be confirmed by a consecutive second (confirmatory) evaluation meeting the criteria for response that is performed at least 4 weeks after the criteria for response are first met. When Stable Disease (SD) is believed to be the best response, it must meet a minimum SD duration of 49 days. Measurements must have met the SD criteria at least once after study entry.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiation and Chemotherapy With Ipilimumab Followed by Nivolumab for Patients With Stage III Unresectable Non-Small Cell Lung Cancer (NSCLC)
Official Title  ICMJE Radiation and Chemotherapy With Ipilimumab Followed by Nivolumab for Patients With Stage III Unresectable NSCLC
Brief Summary This study is to determine if Stage III NSCLC patients treated with ipilimumab with thoracic radiation therapy followed by nivolumab monotherapy every 4 weeks for up to 12 months show an improved 12-month Progression Free Survival (PFS) rate compared with a 12-month historical PFS rate of 49% among patients treated in a similar fashion with concurrent chemoradiotherapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Radiation: Thoracic Radiotherapy
    2 Gy in 30 fractions directed at all sites of suspected disease
  • Drug: Platinum Based Chemotherapy
    Platinum based chemotherapy including cisplatin and etoposide, carboplatin and paclitaxel or cisplatin and pemetrexed (for patients with non-squamous histology).
  • Drug: Ipilimumab
    Iplimamab 1mg/kg delivered concurrently with initiation of chemoradiotherapy and in week 4 of chemoradiotherapy
  • Drug: Nivolumab
    Nivolumab 480 mg (30 minute IV infusion) at least 7 days but no more than 21 days after completion of radiation and chemotherapy every 4 weeks for up to 12 cycles.
Study Arms  ICMJE
  • Experimental: Radiation and Chemotherapy
    Thoracic Radiotherapy with cytotoxic platinum based chemotherapy with cytotoxic platinum based chemotherapy including cisplatin and etoposide, carboplatin and paclitaxel or cisplatin and pemetrexed (for patients with non-squamous histology) and Ipilimumab.
    Interventions:
    • Radiation: Thoracic Radiotherapy
    • Drug: Platinum Based Chemotherapy
    • Drug: Ipilimumab
  • Experimental: Nivolumab
    Nivolumab 480 mg (30 minute IV infusion) after completion of radiation and chemotherapy for up to 12 cycles until progression.
    Intervention: Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2027
Estimated Primary Completion Date March 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Over 18 years of age
  • Participants must have signed and dated a written informed consent form.
  • Participants must be willing and able to comply with proposed visit and treatment schedule.
  • Patients with NSCLC documented by histology or cytology from brushing, washing, or needle aspiration of a defined lesion, but not from sputum cytology alone.
  • Patients must have presented at initial diagnosis with Stage III disease according to American Joint Committee on Cancer (AJCC) Staging Manual, 8th Edition;
  • Patients must be deemed by the treating investigator to be surgically unresectable. I
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
  • Patients must initiate study treatment 60 days from the date of pathologic diagnosis.
  • Tumor biopsy specimen including at least formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or 10 unstained slides of tumor sample (archival or recent) for biomarker evaluation must be available for submission to the central lab for correlative studies.
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 14 days prior to the start of thoracic radiation therapy.
  • Male participants must be willing to refrain from sperm donation during the entire study and for 5 half-lives of study drug plus 90 days (duration of sperm turnover).
  • Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception which have a failure rate of </= 1% when used consistently and correctly. Azoospermic males are exempt from contraceptive requirements.
  • WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug (half-life up to 25 days) plus 30 days (duration of ovulatory cycle) for a total of 5 months post-treatment completion.
  • WOCBP who are continuously not heterosexually active are exempt from contraception requirements. However, they must still undergo pregnancy testing as described in this section.
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of the study drug (half-life up to 25 days) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion

Exclusion Criteria:

  • All toxicities attributed to prior anti-cancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 4) or baseline before administration of study drug(s). Exceptions may apply.
  • Women who are pregnant or breastfeeding
  • Active, known, or suspected autoimmune disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded. Patients 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
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study initiation. Corticosteroids with minimal systemic absorption (inhaled or topical steroids) and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
  • Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody
  • Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  • Any patient requiring supplemental oxygen therapy.
  • Previous malignancies (except non-melanoma skin cancers, and some in situ cancers) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
  • Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug(s) administration or interfere with the interpretation of safety results
  • Major surgery or significant traumatic injury that is not recovered at least 14 days before the initiation of thoracic radiation therapy.
  • Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. Individuals with a positive test for HCV antibody but no detection of HCV RNA indicating no current infection are eligible.
  • Known medical history of testing positive for human immunodeficiency virus (HIV) or known medical history of acquired immunodeficiency syndrome (AIDS)
  • Inadequate hematologic function.
  • Inadequate hepatic function.
  • Inadequate pancreatic function.
  • History of allergy or hypersensitivity to any of the study drugs or study drug components
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03663166
Other Study ID Numbers  ICMJE MCC-19704
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bradford Perez, MD H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP