Trametinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

NCT01912625 | Terminated Phase 1

• 9 other identifiers: NCI-2013-013572012-10537630939448P30CA016672P50CA070907U01CA062461UM1CA186688UM1CA186712
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 5

Brief Summary

This phase I trial studies the side effects and the best dose of trametinib when given together with combination chemotherapy and radiation therapy in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Radiation therapy uses high energy x-rays to kill tumor cells. Giving trametinib, combination chemotherapy, and radiation therapy may be a better treatment for non-small cell lung cancer.

Conditions

Recurrent Lung Non-Small Cell Carcinoma; Stage III Lung Non-Small Cell Cancer AJCC v7; Stage IIIA Lung Non-Small Cell Cancer AJCC v7; Stage IIIB Lung Non-Small Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity defined as any grade 3 or 4 non-hematologic toxicities according to Common Terminology Criteria for Adverse Events version 4.0 grading

  Toxicity will be tabulated by dose, type, and grade. The probability of toxicity over 70 days as a function of dose will be estimated by fitting a Bayesian binary outcome regression model.

  Within 70 days from the start of radiation therapy

• Pharmacokinetic parameters of carboplatin and paclitaxel with the dosing of trametinib

  At 15 and 30 minutes prior to the start of infusion and then at 30 minutes, 4, 10, and 24 hours after infusion on day 15

Secondary Outcomes (4)

• Response rate based on CT or FDG-PET/CT imaging response assessment after completion of chemoradiation

  Up to 4 years

• Overall survival (OS)

  Up to 4 years

• Patterns of recurrence

  Up to 4 years

• KRAS mutation status

  Baseline

Study Arms (1)

Treatment (trametinib, chemotherapy, radiation therapy)

EXPERIMENTAL

CONCURRENT CHEMOTHERAPY: Patients undergo IMRT or 3D-CRT QD 5 days a week for 6 weeks. Patients receive trametinib PO QD and carboplatin IV over 30 minutes and paclitaxel IV over 1 hour once weekly. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients without disease progression after completion of chemoradiation proceed to consolidation chemotherapy. CONSOLIDATION CHEMOTHERAPY: Beginning 3 weeks after completion of concurrent chemoradiation, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 1 and 22. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Carboplatin; Radiation: Image Guided Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study; Drug: Trametinib

Interventions

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo 3D-CRT

Also known as: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D radiotherapy, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy, Radiation, 3D Conformal, Three dimensional external beam radiation therapy (procedure)

Treatment (trametinib, chemotherapy, radiation therapy)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (trametinib, chemotherapy, radiation therapy)

Image Guided Radiation Therapy RADIATION

Undergo IGRT

Also known as: IGRT, image-guided radiation therapy, Image-Guided Radiotherapy

Treatment (trametinib, chemotherapy, radiation therapy)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Treatment (trametinib, chemotherapy, radiation therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (trametinib, chemotherapy, radiation therapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (trametinib, chemotherapy, radiation therapy)

Pharmacological Study OTHER

Correlative studies

Treatment (trametinib, chemotherapy, radiation therapy)

Trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212

Treatment (trametinib, chemotherapy, radiation therapy)

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 confirmed, newly diagnosed or recurrent from a previously treated early stage lung cancers that are locally confined, non-small cell lung cancers that are considered unresectable and for which chemoradiation will be considered definitive therapy; patients with recurrent cancer that is amendable for chemoradiation can be eligible only if patients with prior lobectomy for stage I cancer had not had adjuvant chemotherapy, and more than 8 weeks have elapsed from surgery to allow for wound healing; patients who recur from prior X-ray therapy (XRT) or stereotactic body radiation therapy (SBRT) will not 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 with conventional techniques or as \>= 10 mm with spiral CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Prior thoracic radiation allowed only if there is minimal to no overlap with the treatment area estimated at the time of consultation, and there is no cumulative esophageal dose that exceeds more than 50% of the maximal acceptable dose tolerance
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Life expectancy of greater than 6 months
• Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin \>= 9 g/dL
• Platelets \>= 100 x 10\^9/L
• Albumin \>= 2.5 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional ULN
• Serum creatinine =\< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 50 mL/min OR 24-hour urine creatinine clearance \>= 50 mL/min
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 x institutional ULN
• Left ventricular ejection fraction \>= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)

You may not qualify if:

• History of another malignancy
• Exception: patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the Cancer Therapy Evaluation Program (CTEP) Medical Monitor if unsure whether second malignancies meet the requirements specified above
• History of interstitial lung disease or pneumonitis
• Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to enrollment
• Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib and during the study
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO) or to either carboplatin or paclitaxel
• Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
• Other anti-cancer therapy while on study treatment; (note: megestrol \[Megace\] if used as an appetite stimulant is allowed)
• Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
• Concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra \[ma huang\], gingko biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, or ginseng)
• History or current evidence/risk of retinal vein occlusion (RVO)
• History or evidence of cardiovascular risk including any of the following:
• Left ventricular ejection fraction (LVEF) \< LLN
• A QT interval corrected for heart rate using the Bazett's formula corrected QT (QTcB) \>= 480 msec
• History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for \> 30 days prior to registration are eligible)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy, Conformal; Carboplatin; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated; Paclitaxel; Taxes; trametinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Steven H Lin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2013
• First Posted: July 31, 2013
• Study Start: October 28, 2013
• Primary Completion: November 3, 2017
• Study Completion: February 24, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Locations

US (5)