Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

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

Laboratory Biomarker Analysis

Pharmacological Study

Sapanisertib

Paul K Paik

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.

PRIMARY OBJECTIVE:

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.

Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer

A Phase 2 Study of MLN0128 (TAK-228) in Patients With Advanced Non-Small Cell Lung Cancers Harboring NFE2L2 and KEAP1 Mutations

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. Overall response rate was determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Median progression-free survival will be estimated using the Kaplan-Meier method with a two-sided 95% confidence interval. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a unequivocal increase in a non-target lesion, or the appearance of new lesions

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.

National Cancer Institute (NCI)

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

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Sapanisertib: Given PO

Treatment (Sapanisertib)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Paul Paik, MD

NFEL2 Squamous Cohort

KEAP1 Squamous Cohort

KRAS/NFE2L2 or KEAP1 NSCLC Cohort

The number of participants analyzed for ORR is the response evaluable cohort as defined by the protocol, which is a subset of the total study population reflected in the participant flow module.

Objective Response Rate (Complete Response [CR] + Partial Response [PR])

PFS in the secondary outcome section is the response evaluable cohort, which is a subset of the total study population.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer	NCT02417701	Recurrent Lung ... Stage IV Lung S...	Laboratory Biom... Pharmacological... Sapanisertib	18 Years -	National Cancer Institute (NCI)
Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer	NCT02417701	Recurrent Lung ... Stage IV Lung S...	Laboratory Biom... Pharmacological... Sapanisertib	18 Years -	National Cancer Institute (NCI)
Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer	NCT02417701	Recurrent Lung ... Stage IV Lung S...	Laboratory Biom... Pharmacological... Sapanisertib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iv lung squamous cell carcinoma ajcc v7