Clinical Trials /

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

NCT03663166

Description:

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.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MCC-19704
  • NCT ID: NCT03663166

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
Platinum Based ChemotherapyRadiation and Chemotherapy
IpilimumabRadiation and Chemotherapy
NivolumabNivolumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Radiation and ChemotherapyExperimentalThoracic 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.
  • Platinum Based Chemotherapy
  • Ipilimumab
NivolumabExperimentalNivolumab 480 mg (30 minute IV infusion) after completion of radiation and chemotherapy for up to 12 cycles until progression.
  • Nivolumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Unacceptable toxicity status at the end of 8-week safety observation period
Time Frame:At 8 weeks of treatment
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:12 month distant metastasis free survival (DMFS)
Time Frame:12 months post treatment
Safety Issue:
Description: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.
Measure:Objective Response Rate (ORR) at 6 months
Time Frame:6 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Lung
  • Unresectable NSCLC
  • Radiation

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