Clinical Trials /

Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer

NCT02417701

Description:

This phase II trial studies how well sapanisertib works in treating patients with lung cancer that is stage IV or has come back (recurrent) and has a mutation in the NFE2L2, KEAP-1, or KRAS gene. Damage to these genes may cause the cancer to grow. Sapanisertib may stop this from happening by blocking enzymes.

Related Conditions:
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer
  • Official Title: A Phase 2 Study of MLN0128 (TAK-228) in Patients With Advanced Non-Small Cell Lung Cancers Harboring NFE2L2 and KEAP1 Mutations

Clinical Trial IDs

  • ORG STUDY ID: NCI-2015-00545
  • SECONDARY ID: NCI-2015-00545
  • SECONDARY ID: 2015-00500
  • SECONDARY ID: 15-249
  • SECONDARY ID: 9780
  • SECONDARY ID: 9780
  • SECONDARY ID: P30CA008748
  • NCT ID: NCT02417701

Conditions

  • KEAP1 Gene Mutation
  • KRAS Gene Mutation
  • NFE2L2 Gene Mutation
  • Recurrent Squamous Cell Lung Carcinoma
  • Stage IV Squamous Cell Lung Carcinoma AJCC v7

Interventions

DrugSynonymsArms
SapanisertibINK-128, INK128, MLN-0128, MLN0128, TAK-228Treatment (sapanisertib)

Purpose

This phase II trial studies how well sapanisertib works in treating patients with lung cancer that is stage IV or has come back (recurrent) and has a mutation in the NFE2L2, KEAP-1, or KRAS gene. Damage to these genes may cause the cancer to grow. Sapanisertib may stop this from happening by blocking enzymes.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the overall response rate of the TORC1/TORC2 inhibitor sapanisertib (MLN0128
      [TAK-228]) in stage IV squamous cell lung cancers or KRAS mutant lung cancers harboring
      NFE2L2 or KEAP1 mutations.

      SECONDARY OBJECTIVES:

      I. To evaluate the median progression free survival of patients in each cohort. II. To
      explore the feasibility of performing reverse phase protein array analysis (RPPA) in paired
      snap-frozen core biopsies from patients in this study prior to MLN0128 (TAK-228) dosing and
      during week 2 of treatment.

      III. To describe the effectiveness of MLN0128 (TAK-228) in suppressing activation of mTOR and
      PI3K signaling through the exploratory RPPA analysis.

      OUTLINE:

      Patients receive sapanisertib orally (PO) once daily (QD) on days 1-28. Cycles repeat every
      28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 4 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (sapanisertib)ExperimentalPatients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Sapanisertib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed stage IV or recurrent
             squamous cell lung cancer or KRAS mutant lung cancer that harbors any of the NFE2L2
             mutations or KEAP1 mutations; any KEAP1 mutation will be eligible

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with
             conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT)
             scan, magnetic resonance imaging (MRI), or calipers by clinical exam

          -  Patients must have completed at least 1 prior line of systemic therapy; patients who
             have declined first line therapy or for whom first-line therapy would be clinically
             inappropriate, will be considered eligible for the trial

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Life expectancy of greater than 3 months

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Fasting serum glucose =< 130 mg/dL

          -  Hemoglobin A1C (HBA1C) < 7.0%

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 50
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Patients with controlled diabetes are allowed on study; controlled diabetes is defined
             as fetal bovine serum (FBS) =< 130 mg/dL in the context of this study

          -  The effects of MLN0128 (TAK-228) on the developing human fetus are unknown; for this
             reason women of child-bearing potential and men must agree to practice 1 highly
             effective method of contraception and 1 additional effective (barrier) method, at the
             same time, prior to study through 90 days (or longer, as mandated by local labeling
             [eg, USPI, SmPC, etc;]) after the last dose of study drug; should a woman become
             pregnant or suspect she is pregnant while she or her partner is participating in this
             study, she should inform her treating physician immediately; any woman who becomes
             pregnant while receiving MLN0128 (TAK-228) will be removed from the trial; men treated
             or enrolled on this protocol must also agree to use highly effective barrier
             contraception prior to the study, for the duration of study participation, and 120
             days after completion of MLN0128 (TAK-228) administration; men must agree not to
             donate sperm during the course of this study or within 120 days after receiving their
             last dose of study drug

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Ability to swallow oral medications

          -  Known human immunodeficiency virus (HIV) positive patients who meet the following
             criteria will be considered eligible:

               -  CD4 count > 350 cells/mm3

               -  Undetectable viral load

               -  Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 2 weeks prior to the planned
             start of study treatment or those who have not recovered to baseline or less than
             grade 2 from adverse events from prior treatments

          -  Patients who are receiving any other investigational agents

          -  Patients with untreated central nervous system (CNS) metastases; patients with treated
             CNS metastases who are off steroids are eligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MLN0128 (TAK-228)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements; no ischemic myocardial or cerebrovascular event, class III or IV
             heart failure, placement of pacemaker, or pulmonary embolism within six months of
             receiving first dose of MLN0128 (TAK-228)

          -  Baseline prolongation of the rate-corrected QT interval (QTc) > 480 milliseconds, or
             history of congenital long QT syndrome, or torsades de pointes

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with MLN0128

          -  Patients previously treated with an mammalian TOR (mTOR) or PI3K inhibitor

          -  Concomitant administration of any proton pump inhibitor (PPI) is not permitted during
             the study; patients receiving PPI therapy before enrollment must stop using the PPI
             for 7 days before their first dose of study drugs

          -  Uncontrolled diabetes mellitus (fasting plasma glucose > 130 mg/dL despite optimal
             medical management of hyperglycemia)

          -  Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
             infection

          -  Patients receiving histamine H2 receptor antagonists before enrollment must stop using
             these medications for at least 24 hours before their first dose of study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (complete response [CR] + partial response [PR])
Time Frame:Up to 4 weeks after completion of study treatment
Safety Issue:
Description:Overall response rate (CR+PR) will be calculated separately for each cohort, including exact 95% confidence intervals. Duration of overall response and duration of stable disease will be calculated and summarized.

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:From start of treatment up to 4 weeks after completion of study treatment
Safety Issue:
Description:Median progression-free survival will be estimated using the Kaplan-Meier method with a two-sided 95% confidence interval.
Measure:Feasibility of reverse phase protein array analysis, defined as the ability to procure sufficient quantity and quality of tumor protein for sample
Time Frame:Up to week 2
Safety Issue:
Description:Single target signaling changes will be reported as percentages relative to the baseline pre-treatment tumor sample. Larger scale pathway changes will qualitatively represented through heatmaps.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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