Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer

NCT02417701 | Completed Phase 2 Results DMC

• 5 other identifiers: NCI-2015-0054515-2492015-005009780P30CA008748
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  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.

  CT imaging was obtained after every 2 cycles, or 8 weeks, starting from cycle 1 day 1 until end of study treatment, up to 1 year.

Secondary Outcomes (2)

• Progression-free Survival

  From start of treatment (cycle 1 day 1) until the date of first documented progression or death, over the trial enrollment period, up to 1 year.

• Feasibility of Reverse Phase Protein Array Analysis, Defined as the Ability to Procure Sufficient Quantity and Quality of Tumor Protein for Sample

  Up to week 2

Study Arms (1)

Treatment (sapanisertib)

EXPERIMENTAL

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

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sapanisertib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sapanisertib)

Pharmacological Study OTHER

Correlative studies

Treatment (sapanisertib)

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Treatment (sapanisertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 or 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 \[e.g., United States Package Insert (USPI), Summary of Product Characteristics (SmPC), etc;\]) 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

You may not qualify if:

• 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 because MLN0128 (TAK-228) is an mTOR agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MLN0128 (TAK-228), breastfeeding should be discontinued if the mother is treated with MLN0128 (TAK-228)
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

MeSH Terms

Interventions

sapanisertib

Results Point of Contact

• Title: Dr. Paul Paik, MD
• Organization: Memorial Sloan Kettering Cancer Center

paikp@mskcc.org

646-608-3759

Study Officials

• Paul K Paik

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: April 16, 2015
• Study Start: October 6, 2016
• Primary Completion: December 28, 2020
• Study Completion: December 28, 2020
• Last Updated: April 5, 2022
• Results First Posted: April 5, 2022

Record last verified: 2022-03

Locations

US (7)