Clinical Trials /

Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs

NCT02350764

Description:

The purpose of this study is to closely examine tumor and blood samples from patients treated with nivolumab and ipilimumab in order to try to identify why some patients with lung cancers respond and why some patients do not.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs
  • Official Title: An Exploratory Study to Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs

Clinical Trial IDs

  • ORG STUDY ID: 14-137
  • NCT ID: NCT02350764

Conditions

  • Advanced Stage Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
nivolumabNivolumab
pilimumabNivolumab

Purpose

The purpose of this study is to closely examine tumor and blood samples from patients treated with nivolumab and ipilimumab in order to try to identify why some patients with lung cancers respond and why some patients do not.

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimentalPatients will begin treatment with nivolumab IV 3mg/kg and ipilimumab 1mg/kg. Treatment with nivolumab will continue every 2 weeks (+/- 3 days) thereafter and treatment with ipilimumab will continue every 6 weeks (+/- 3 days) thereafter. Treatment will continue until protocol-defined toxicity, confirmed progression of disease*, withdrawal of consent, or death.
  • nivolumab
  • pilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must be capable, willing, and able to provide written, informed consent.

          -  ≥ 18 years old.

          -  Advanced stage NSCLC

          -  Previously treated with no more than two lines of prior systemic therapy for advanced
             stage lung cancer.

               -  Patients who previously received neoadjuvant, concurrent, or adjuvant
                  chemotherapy for localized NSCLC and then recurred within 6 months of completing
                  chemotherapy may be considered as having received one line of prior therapy

               -  Maintenance therapy does not count as a separate line of therapy

          -  Patients must:

               -  Be scheduled to undergo a standard-of-care resection of tumor tissue as part of
                  treatment plan prior to beginning study therapy. Patients may not have
                  intervening systemic anti-cancer therapy between the time of resection and
                  treatment with nivolumab.

               -  Have collection of adequate pre-treatment tissue for correlative analysis defined
                  as sufficient material for 1) frozen tissue for DNA/RNA with touch
                  prep/representative slide confirming tumor material present, 2) FFPE material for
                  ICH with touch prep/representative slide confirming tumor material present, and
                  3) single-cell suspensions with >20 million live cells after tissue digestion but
                  before freezing. Adequacy of collected material will be determined within 5
                  business days of each collected case.

               -  Have residual disease following surgical resection that is measurable by RECIST
                  v1.1

               -  Previously irradiated sites of tumor may be considered measurable if there is
                  radiographic progression at that site subsequent to the time of completing
                  radiation.

               -  Have a safely biopsiable tumor lesion

          -  ECOG performance status of 0-1.

          -  Adequate hematologic, renal, and/or hepatic function (following criteria must be met
             within 28 days of C1D1:

               -  WBC ≥ 2,000/ul

               -  ANC ≥ 1,500/ul

               -  Hemoglobin ≥ 9.0 g/dl

               -  Platelet count ≥ 100,000/ul

               -  Total bilirubin ≤ 1.5 x ULN (unless evidence of Gilbert's syndrome, in which
                  case, direct bilirubin must be ≤ 1.0 x ULN)

               -  AST and ALT ≤ 3 x UNL (unless elevated transaminases are felt to be directly
                  related to metastatic disease involving the liver, in which case AST and ALT must
                  be ≤ 5x ULN)

               -  Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance of ≥ 40 mL/min
                  calculated using the formula of Cockcroft and Gault: (140-Age) • Mass (kg)/(72 •
                  creatinine mg/dL); multiply by 0.85 if female

          -  There is no restriction on the number of prior lines of systemic anti-cancer therapy.
             For those who have received prior systemic anti-cancer therapy, there must be at least
             3 weeks since last systemic therapy.

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 3 days prior to
             the start of study drug.

          -  Effective contraception:

               -  Women of childbearing potential must agree to practice 2 effective methods of
                  contraception from the time of signing the informed consent form through 23 weeks
                  (5 half-lifes plus 30 days, the duration of an ovulatory cycle) after the last
                  dose of nivolumab, or agree to completely abstain from heterosexual intercourse.

               -  Male subjects, even if surgically sterilized (i.e., status post vasectomy) must
                  agree to 1 of the following: practice effective barrier contraception during the
                  entire study treatment period and through 31 weeks (5 half-lives plus 90 days,
                  the duration of sperm turnover) after the last dose of study drug, or completely
                  abstain from heterosexual intercourse.

        Exclusion Criteria:

          -  Patients who are pregnant or lactating.

          -  Presence of activating EGFR mutations or ALK re-arrangement,unless previously treated
             with standard TKI therapy. All patients with adenocarcinoma histology must be tested
             for EGFR and ALK status.

          -  History of allergy to study drug components or history of severe hypersensitivity
             reaction of any monoclonal antibody.

          -  Prior treatment with immune checkpoint inhibitor, including (but not limited to) those
             targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137, GITR, TIM3, LAG3, or OX40

          -  Any systemic anti-cancer therapy within 3 weeks prior to C1D1 of study therapy

          -  Exception is made for patients with EGFR or ALK re-arrangements who must have stopped
             TKI therapy at least 7 days prior to C1D1

          -  Patients who have not previously been treated with platinum-based based doublet
             chemotherapy and who, in the judgment of the investigator, have rapidly progressive
             disease such that serious complications may arise from disease progression within the
             next 12 weeks will be excluded.

          -  Non-CNS radiotherapy within 1 week prior to C1D1 of study therapy

          -  Active infection requiring therapy

          -  Prior systemic immunosuppressive therapy (> 10 mg/day prednisone equivalents) within 1
             week prior to C1D1 of study therapy. Inhaled, ocular, intra-articular, intranasal, and
             topical corticosteroids are permitted in absence of active autoimmune disease.

               -  Adrenal replacement doses are permitted in the absence of active autoimmune
                  disease.

          -  Patients with known or suspected history of autoimmune disease. Subjects with type I
             diabetes melitis, hypothyroidism only requiring hormone replacement, resolved
             childhood asthma/atopy, patients with asthma requiring intermittent bronchodilator
             therapy, 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.

          -  Other active malignancy requiring concurrent intervention.

          -  Patients with previous malignancies (except non-melanoma skin cancers, and the
             following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or
             breast) are excluded unless definitive therapy has been completed at least 1 year
             prior to study entry and the patient is now without evidence of disease from that
             malignance and no additional therapy is required or anticipated to be required during
             the study period.

          -  Known untreated brain or leptomeningeal metastasis.

             o Patients with brain metastases are eligible if metastases have been adequately
             treated and neurologically returned to baseline (except for residual signs or symptoms
             related to the CNS treatment) for at least two weeks prior to C1D1. In addition, 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.

          -  Patients with interstitial lung disease that is symptomatic or may interfere with the
             detection or management of suspected drug-related pulmonary toxicity.

          -  Any positive test for HIV

          -  Any positive test for HCV RNA or HBsAg.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall response rate (confirmed partial + complete response) will be assessed as part of this study. Tumor response will be assessed using RECIST 1.1)
Time Frame:every 6 weeks (+/- 1 week) until week 48
Safety Issue:
Description:confirmed partial + complete response will be assessed as part of this study. Tumor response will be assessed using RECIST 1.1. All responses must be confirmed on subsequent scan to be considered a true response. Tumor assessments will be performed after.6 weeks (+/- 1 week) and subsequently every six week (+/- 1 week) thereafter while on study until week 48. After week 48, tumor assessments will be conducted every 12 weeks (+/- week). Additional tumor assessments may be performed at the discretion of the treating physician.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Nivolumab
  • Lung
  • ipilimumab
  • NSCLC
  • 14-137

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