Clinical Trials /

Durvalumab and Tremelimumab in Treating Patients With Recurrent Stage IV Lung Cancer

NCT03373760

Description:

This phase II trial studies how well durvalumab and tremelimumab works in treating patients with stage IV lung cancer that has come back after previous treatment. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab and Tremelimumab in Treating Patients With Recurrent Stage IV Lung Cancer
  • Official Title: A Phase II Study of MEDI4736 (Durvalumab) Plus Tremelimumab as Therapy for Patients With Previously Treated Anti-PD-1/PD-L1 Resistant Stage IV Squamous Cell Lung Cancer (Lung-Map Non-Match Sub-Study)

Clinical Trial IDs

  • ORG STUDY ID: S1400F
  • SECONDARY ID: NCI-2016-01597
  • SECONDARY ID: S1400F
  • SECONDARY ID: S1400F
  • SECONDARY ID: S1400F
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT03373760

Conditions

  • Recurrent Squamous Cell Lung Carcinoma
  • Stage IV Squamous Cell Lung Carcinoma AJCC v7

Interventions

DrugSynonymsArms
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Treatment (tremelimumab, durvalumab)
TremelimumabAnti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, ticilimumabTreatment (tremelimumab, durvalumab)

Purpose

This phase II trial studies how well durvalumab and tremelimumab works in treating patients with stage IV lung cancer that has come back after previous treatment. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the objective response rate (confirmed and unconfirmed, complete and partial)
      by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among patients treated with
      durvalumab (MEDI4736) plus tremelimumab.

      SECONDARY OBJECTIVES:

      I. To estimate the duration of response (DoR) among patients who achieve a complete response
      (CR) or partial response (PR) (confirmed and unconfirmed) by RECIST 1.1.

      II. To estimate the duration of response (DoR) per immune-related response criteria among
      patients who achieve a complete response (CR) or partial response (PR) (confirmed and
      unconfirmed) by RECIST 1.1.

      III. To evaluate overall survival (OS) among patients treated with durvalumab (MEDI4736) plus
      tremelimumab.

      IV. To evaluate investigator-assessed progression-free survival (IA-PFS) among patients
      treated with durvalumab (MEDI4736) plus tremelimumab.

      V. To evaluate IA-PFS assessed by immune-related response criteria (irRC-IA-PFS) among
      patients treated with durvalumab (MEDI4736) plus tremelimumab.

      VI. To evaluate the frequency and severity of toxicities associated with durvalumab
      (MEDI4736) plus tremelimumab.

      TERTIARY OBJECTIVES:

      I. To explore the association of potential predictive markers identified in S1400A, with
      response and progression-free survival (PFS).

      II. To explore the association of PD-L1 expression status with response and PFS.

      III. To contribute to an ongoing serum and tumor bank in S1400.

      OUTLINE:

      Patients receive tremelimumab intravenously (IV) over 60 minutes on day 1 for courses 1-4 and
      durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for 2 years, and
      then at the end of year 3.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (tremelimumab, durvalumab)ExperimentalPatients receive tremelimumab IV over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Durvalumab
  • Tremelimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have been assigned to S1400F

          -  Patients must have progressed during or after prior platinum-based chemotherapy;
             patients whose only prior platinum-based chemotherapy regimen was for stage I-III
             disease (i.e. patient has not received any platinum-based chemotherapy for stage IV or
             recurrent disease), disease progression on platinum-based chemotherapy must have
             occurred within one year from the last date that patient received that therapy;
             patients must have experienced disease progression during or after prior anti-PD-1 or
             anti-PD-L1 antibody monotherapy as their most recent line of treatment; prior
             PD-1/PD-L1 combination therapy is not permitted

          -  Prior exposure to CTLA-4 inhibitors (ipilimumab and tremelimumab) is not permitted;
             prior exposure to the following is allowed: attenuated vaccines, anti-EGFR agents, and
             granulocyte-macrophage colony-stimulating factor (GM-CSF)

          -  Patients must not have received nitrosoureas or mitomycin-C within 42 days prior to
             sub-study registration

          -  Patients must not have any prior documented autoimmune or inflammatory disease
             (including inflammatory bowel disease, diverticulitis with the exception of
             diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto
             syndrome) within 3 years prior to sub-study registration; patients with vitiligo,
             immune-mediated alopecia, Grave?s disease, or psoriasis requiring systemic treatment
             within the past 2 years are not eligible; patients with hypothyroidism (e.g. post
             Hashimoto syndrome) who are stable on hormone replacement therapy are eligible

          -  Patients must not have any history of primary immunodeficiency

          -  Patients must not have received any immunosuppressive medication within 28 days prior
             to sub-study registration and must not be planning to receive these medications while
             on protocol therapy; systemic corticosteroids must be stopped at least 24 hours prior
             to sub-study registration; however, intranasal and inhaled corticosteroids are allowed
             at any time before and during protocol therapy

          -  Patients must not have experienced a grade 3 or worse immune-related adverse event
             (irAE) (except asymptomatic nonbullous/nonexfoliative rash) or any unresolved irAE
             grade 2, nor have experienced a toxicity that led to permanent discontinuation of
             prior anti-PD-1/PD-L1 immunotherapy

          -  Patients must not have any history of organ transplant that requires use of
             immunosuppressives

          -  Patients must not have any known allergy or reaction to any component of the
             durvalumab (MEDI4736) and/or tremelimumab formulation

          -  Patients must not have clinical signs or symptoms of active tuberculosis infection

          -  Patients must not have received a live attenuated vaccination within 28 days prior to
             sub-study registration

          -  Patients must not have known human immunodeficiency virus (HIV), or a known positive
             test for hepatitis B virus surface antigen (HBV sAg), or hepatitis C virus ribonucleic
             acid (HCV antibody) indicating current acute or chronic infection; patients with a
             positive hepatitis C antibody with a negative viral load are allowed

          -  Patients must have a thyroid-stimulating hormone (TSH) with reflex free T3/free T4 (if
             TSH is out of normal range) and electrocardiogram (EKG) obtained within 7 days prior
             to sub-study registration

          -  Patients must also be offered participation in banking and in the correlative studies
             for collection and future use of specimens
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time Frame:Up to 3 years
Safety Issue:
Description:Estimated within 13% with 95% confidence.

Secondary Outcome Measures

Measure:Duration of response (DOR)
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median DOR.
Measure:Immune-Related Response Criteria investigator-assessed progression-free survival (irRC-IA-PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time Frame:From date of registration to date of first documentation of irRC progression or death due to any cause, assessed up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier.
Measure:Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 3 years
Safety Issue:
Description:Toxicity rates can be estimated within 13% with 95% confidence. Any toxicity with at least 5% prevalence has at least a 95% chance of being observed.
Measure:Investigator-assessed progression-free survival (IA-PFS)
Time Frame:6 months after completion of accrual
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median IA-PFS.
Measure:Overall survival (OS)
Time Frame:6 months after completion of accrual
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median OS.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

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