Testing of TAK228 (MLN0128, Sapanisertib) Plus Docetaxel to the Usual Standard of Care for Advanced Squamous Cell Lung Cancer (A Lung-MAP Treatment Trial)

NCT04267913 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: S1900DNCI-2020-00171U10CA180888
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II LUNG-MAP treatment trial studies how well sapanisertib and docetaxel work for the treatment for squamous cell lung cancer that is stage IV or has come back (recurrent). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving sapanisertib and docetaxel may work better in treating patients with squamous cell lung cancer compared to standard chemotherapy.

Conditions

Lung Squamous Cell Carcinoma; Recurrent Lung Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Investigator-assessed progression-free survival (IA-PFS)

  IA-PFS will be compared between the arms using a stratified log-rank test.

  Up to 3 years

Secondary Outcomes (4)

• Overall response rate (ORR)

  Up to 3 years

• Duration of response

  Up to 3 years

• Progression free survival

  Up to 3 years

• Overall survival

  Up to 3 years

Study Arms (2)

Arm A (docetaxel, dexamethasone, sapanisertib)

EXPERIMENTAL

Patients receive docetaxel IV and dexamethasone IV over 30 minutes on days 1 and 8 and sapanisertib PO QD on days 2-4, 9-11, and 16-18. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. If docetaxel is discontinued, patients receive sapanisertib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Docetaxel; Drug: Sapanisertib

Arm B (standard of care treatment)

ACTIVE COMPARATOR

Patients receive standard of care treatment comprising either docetaxel IV and dexamethasone IV over 30 minutes on day 1 or docetaxel IV, dexamethasone IV over 30 minutes, and ramucirumab IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Docetaxel; Biological: Ramucirumab; Drug: Sapanisertib

Interventions

Dexamethasone DRUG

Given IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm A (docetaxel, dexamethasone, sapanisertib); Arm B (standard of care treatment)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Arm A (docetaxel, dexamethasone, sapanisertib); Arm B (standard of care treatment)

Ramucirumab BIOLOGICAL

Given IV

Also known as: Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2

Arm B (standard of care treatment)

Sapanisertib DRUG

Given PO

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

Arm A (docetaxel, dexamethasone, sapanisertib); Arm B (standard of care treatment)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be assigned to S1900D. Assignment to S1900D is determined by the S1400 or LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker eligibility for S1900D is based on the identification of an NFE2L2 mutation or KEAP1 alteration
• Patients must have a histologically or cytologically confirmed stage IV or recurrent pure squamous cell lung cancer
• Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to randomization. CT and MRI scans must be submitted for central review via transfer of images and data (TRIAD)
• Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study randomization
• Patients with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to sub-study randomization
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to sub-study randomization
• Patients with a known history of human immunodeficiency virus (HIV) seropositivity:
• Must have undetectable viral load using standard HIV assays in clinical practice
• Must have CD4 count \>= 400/mcL
• Must not require prophylaxis for any opportunistic infections (i.e., fungal, mycobacterium avium complex \[MAC\], or pneumocystis pneumonia \[PCP\] prophylaxis)
• Must not be newly diagnosed within 12 months prior to sub-study randomization
• Patients must be able to swallow oral medications. Patients must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of TAK228 (MLN0128, sapanisertib) (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection, or enteric stomata)
• Patients must be able to safely receive at least one of the investigator's choice of standard of care regimens
• Patients must have progressed (in the opinion of the treating physician) following the most recent line of therapy
• Patients must have recovered (=\< grade 1) from any side effects of prior therapy

You may not qualify if:

• Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS 1 gene rearrangement, and BRAF V600E mutation unless they have progressed following all standard of care targeted therapy
• Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to sub-study randomization, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 14 days prior to sub-study randomization. Patients with brain metastases that have not been treated may be registered if the metastases are:
• \< 2 mm OR deemed clinically equivocal, AND
• No evidence of shift, AND
• No focal or other neurologic deficits, AND
• No requirement for steroids, anti-seizure medications
• Patients must not have uncontrolled illnesses within 28 days prior to sub-study randomization including:
• Uncontrolled asthma is defined as: oxygen (O2) saturation \< 90% by arterial blood gas analysis or pulse oximetry on room air
• Medically significant (symptomatic) bradycardia
• History of arrhythmia requiring an implantable cardiac defibrillator
• Symptomatic pulmonary hypertension
• Uncontrolled hypertension (use of anti-hypertensive agents to control hypertension before cycle 1 day 1 \[C1D1\] is allowed)
• Clinically significant valvular disease
• Patients must not have received any radiation therapy within 14 days prior to randomization
• Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study. Concurrent use of hormones for non-cancer-related conditions (e.g. insulin for diabetes and hormone replacement therapy) is acceptable

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Docetaxel; Ramucirumab; sapanisertib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paul K Paik

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2020
• First Posted: February 13, 2020
• Study Start: September 5, 2020
• Primary Completion: October 31, 2025
• Study Completion (Estimated): October 31, 2026
• Last Updated: November 20, 2020

Record last verified: 2020-11