Clinical Trials /

Phase III Trial of (LCT) After Nivolumab and Ipilimumab

NCT03391869

Description:

This phase III trial studies how well nivolumab and ipilimumab works with or without local consolidation therapy in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Local consolidation therapy, such as surgery or radiation therapy, may improve survival outcomes in patients with non-small cell lung cancer. It is not yet known whether giving nivolumab and ipilimumab with local consolidation therapy works better than nivolumab and ipilimumab alone in treating patients with stage IV non-small cell lung cancer.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Trial of Local Consolidation Therapy (LCT) After Nivolumab and Ipilimumab (LONESTAR)
  • Official Title: Randomized Phase III Trial of Local Consolidation Therapy (LCT) After Nivolumab and Ipilimumab for Immunotherapy-Naive Patients With Metastatic Non-Small Cell Lung Cancer (LONESTAR) -Strategic Alliance: BMS

Clinical Trial IDs

  • ORG STUDY ID: 2017-0311
  • SECONDARY ID: NCI-2018-00825
  • NCT ID: NCT03391869

Conditions

  • Malignant Neoplasms of Respiratory and Intrathoracic Organs
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
IpilimumabYervoy, BMS-734016, MDX010Arm A: Ipilimumab + Nivolumab
NivolumabBMS-936558, OpdivoArm A: Ipilimumab + Nivolumab

Purpose

The goal of this clinical research study is to learn if local consolidation treatment (LCT-- surgery and/or radiation) plus immunotherapy (ipilimumab and nivolumab) is more effective than ipilimumab and nivolumab alone in treating patients with metastatic (has spread) non-small cell lung cancer (NSCLC) who have not previously received immunotherapy. This is an investigational study. LCT is FDA approved and commercially available for the treatment of NSCLC. Nivolumab and ipilimumab are FDA approved and commercially available for treatment of many types of cancer. It is considered investigational to use nivolumab and ipilimumab to treat metastatic NSCLC. The study doctor can explain how the study drugs and LCT are designed to work. Up to 270 participants will be enrolled in this study. All will take part at MD Anderson.

Trial Arms

NameTypeDescriptionInterventions
Arm A: Ipilimumab + NivolumabExperimentalEach study cycle is 6 weeks (42 days). Induction: All participants receive 2 cycles of Ipilimumab and Nivolumab treatment alone. After Induction, participants receive Nivolumab on Days 1, 15, and 29 of each cycle (about every 2 weeks) and Ipilimumab on Day 1 of each cycle (about every 6 weeks) until progression or up to 2 years.
  • Ipilimumab
  • Nivolumab
Arm B: LCT + Ipilimumab + NivolumabExperimentalEach study cycle is 6 weeks (42 days). Induction: All participants receive 2 cycles of Ipilimumab and Nivolumab treatment alone. After Induction, participants receive LCT within 14 days after last dose of Nivolumab during Induction. The study doctor, surgeon, and radiation oncologist will decide if participant will have surgery and/or radiation therapy.
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Age >/= 18

          2. Histologically or cytologically confirmed non-small cell lung cancer. If a diagnostic
             biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected
             lung cancer may be consented, but pathology must be confirmed prior to initiating
             treatment on study. Neuroendocrine carcinomas (e.g. SCLC, carcinoid tumors) are not
             eligible. Carcinomas with neuroendocrine differentiation are eligible.

          3. Stage IV (according to AJCC 8th edition).

          4. Signed and dated written informed consent prior to admission to the study in
             accordance with ICH-GCP guidelines and to the local legislation.

          5. For lung adenocarcinoma patients, patients must be wild-type for EGFR and ALK. For
             patients with histologies other than adenocarcinoma, EGFR and ALK status is not
             required. Adenocarcinoma patients may be consented prior to the EGFR and ALK status
             being known, but EGFR and ALK status must be determined prior to initiating therapy.
             EGFR and ALK status may be determined using either tumor- or plasma-based,
             CLIA-certified assays. For patients with NSCLC, not otherwise specified (NOS),
             EGFR/ALK testing is not required, as the frequency of alterations is exceedingly rare
             in this histology. Also, note that patients with ROS1/RET alterations can be enrolled,
             as TKIs/crizotinib aren't established as first line therapy for patients with these
             alterations.

          6. One prior line of chemotherapy and/or targeted agents for metastatic disease are
             permitted. This chemotherapy can include maintenance therapy, as long as it was given
             in the front line setting. In addition, prior antiangiogenic therapy (e.g.
             bevacizumab) is permitted if used as frontline treatment.

          7. Patients must have organ and marrow function as defined below: a) Performance Status
             of 0 or 1 if using ECOG/Zubrod. b) Screening laboratory values must meet the following
             criteria and should be obtained within 14 days prior to randomization/registration i)
             WBC >/= 2000/µL ii) Neutrophils >/= 1500/µL iii) Platelets >/= 100 x 10 ^3/µL iv)
             Hemoglobin > 9.0 g/dL v) Serum creatinine </=1.5 x ULN or creatinine clearance (CrCl)
             >/= 50 mL (if using the Cockcroft-Gault formula): 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 ÷ 72 x serum creatinine in mg/dL vi) AST/ALT </= 3 x ULN vii)
             Total Bilirubin </= 1.5 x ULN (except subjects with Gilbert Syndrome, who can have
             total bilirubin < 3.0 mg/dL)

          8. Women of childbearing potential (WOCBP) must use appropriate method(s) of
             contraception. Appropriate methods of contraception are as follows. Women will be
             instructed to adhere to contraception for a period of 26 weeks after the last dose of
             investigational product. Men receiving nivolumab and who are sexually active with
             WOCBP will be instructed to adhere to contraception for a period of 35 weeks after the
             last week of nivo/ipi. Note: WOCBP is defined as any female who has experienced
             menarche and who has not yet undergone surgical sterilization (hysterectomy or
             bilateral oophorectomy) or who is not postmenopausal. 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 55 must have a documented
             negative serum or urine test.

          9. Women of childbearing potential must have a negative serum or urine pregnancy test
             within 48 hours prior to the start of nivolumab.

         10. 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 35
             weeks after the last dose of investigational product Women who are not of childbearing
             potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic
             men do not require contraception.

         11. Subjects with brain metastases are eligible if metastases have been treated and there
             is no MRI evidence of disease progression for 4 weeks after treatment is complete and
             within 28 days prior to the first dose of nivolumab. Subjects with asymptomatic brain
             metastases are eligible, though if treated with radiation or surgery the above
             criteria apply regarding a 28-day washout and MRI to assess for progression after 4
             weeks.

         12. Subjects may receive radiotherapy for symptomatic metastases prior to enrollment
             provided that there is at least one other non-irradiated lesion amenable to LCT at the
             time of enrollment. When feasible, stereotactic body radiation therapy (SBRT) or other
             hypofractionated techniques are strongly encouraged.

        Exclusion Criteria:

          1. Systemic immunotherapy for metastatic NSCLC. Immunotherapy agents include, but are not
             limited to, agents targeting the PD1/PD-L1 axis (e.g. nivolumab, pembrolizumab,
             atezolizumab, durvalumab) or CTLA-4 (ipilimumab, tremelimumab) pathways.

          2. Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3
             weeks prior to the initiation of study treatment; the following exceptions are
             allowed: Hormone-replacement therapy or oral contraceptives

          3. Women must not be breastfeeding.

          4. Patients excluded with any prior treatment of pneumonitis requiring corticosteroids.

          5. Unwillingness or inability to follow the procedures required in the protocol.

          6. Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
             may increase the risk associated with study participation or study drug
             administration, impair the ability of the subject to receive protocol therapy, or
             interfere with the interpretation of study results.

          7. Prior malignancy active within the previous 2 years. Patients with locally curable
             cancers that have been apparently cured, such as basal or squamous cell skin cancer,
             superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
             with local control measures (surgery, radiation) are eligible.

          8. Patients should 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.

          9. Patients should be excluded if they have a condition requiring systemic treatment with
             either corticosteroids (> 10 mg daily prednisone equivalents) or other
             immunosuppressive medications within 14 days of study drug administration (i.e.
             disease-modifying antirheumatic drugs). Inhaled or topical steroids and adrenal
             replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of
             active autoimmune disease. Note that subjects are permitted to use topical, ocular,
             intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic
             absorption). Physiologic replacement doses of systemic corticosteroids are permitted,
             even if >10 mg/day prednisone equivalents. A brief course of corticosteroids for
             prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions
             (e.g. delayed-type hypersensitivity reaction caused by contact allergen) is permitted.

         10. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab
             combinations, drugs with a predisposition to hepatoxicity should be used with caution.

         11. Patients should be excluded if they are known to be positive for hepatitis B virus
             surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody)
             indicating acute or chronic infection.

         12. Patients should be excluded if they have known history of testing positive for human
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

         13. History of allergy to study drug components.

         14. History of severe hypersensitivity reaction to any monoclonal antibody.

         15. Prisoners or subjects who are involuntarily incarcerated.

         16. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (infection disease) illness.

         17. Psychological, familial, sociological or geographical factors potentially hampering
             compliance with the study protocol and follow-up schedule.

         18. Any condition that, in the opinion of the investigator, would interfere with the study
             treatment or interpretation of the study results.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:for up to 2 years
Safety Issue:
Description:Overall survival (OS) determined from randomization to a) death or b) last contact date (if alive).

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:up to 2 years
Safety Issue:
Description:Progression-free survival (PFS) determined from randomization to the earliest of the three endpoints: a) progression, b) last imaging study, or c) death Progression measured using RECIST 1.1 criteria.
Measure:Time to Appearance of New Metastases (TANM)
Time Frame:up to 2 years
Safety Issue:
Description:Time to appearance of new metastases (TANM) determined from randomization to the earliest of the two endpoints: a) development of a new lesion, or b) last imaging study per RECIST 1.1 criteria.
Measure:Progression of Target lesions Defined by RECIST 1.1 Criteria
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:Progression of Non-Target Lesions by RECIST 1.1 Criteria
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:Toxicity Evaluated Using CTCAE v4.0 Criteria
Time Frame:up to 2 years
Safety Issue:
Description:Toxicity evaluated using CTCAE v4.0 criteria, with a specific focus on ≥3 toxicity.
Measure:Quality of Life (QOL)
Time Frame:After 12 weeks of therapy and then every 3 months for up to 2 years
Safety Issue:
Description:QOL assessed using the lung-MD Anderson symptom inventory (MDASI-LC) questionnaire in collaboration with the MD Anderson symptom management group, at the following timepoints: 1) prior to induction treatment, 2) prior to randomization, 3) every 12 weeks, and 4) after progression/off study.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasms of respiratory and intrathoracic organs
  • Non-small cell lung cancer
  • NSCLC
  • Ipilimumab
  • Yervoy
  • BMS-734016
  • MDX010
  • Nivolumab
  • BMS-936558
  • Opdivo
  • Local Consolidative Therapy
  • LCT

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