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Recurrent Lung Non-Small Cell CarcinomaPhase 1NCT01912625

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

A Phase 1 study testing 3-Dimensional Conformal Radiation Therapy, Carboplatin and Image Guided Radiation Therapy in people with Recurrent Lung Non-Small Cell Carcinoma and Stage III Lung Non-Small Cell Cancer AJCC v7, run by National Cancer Institute (NCI) at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
3-Dimensional Conformal Radiation Therapy, Carboplatin and Image Guided Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
5 sitesUnited States
Study dates
28 Oct 2013to 24 Feb 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to registration and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; 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
  • Ability to understand and the willingness to sign a written informed consent document
  • Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (any G12, G13, Q61) confirmed by Clinical Laboratory Improvement Act (CLIA)-certified testing
  • The availability of formalin-fixed paraffin embedded archival tissue from core biopsy of tumors is recommended for exploratory analysis

Who cannot join

  • 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
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  • 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)
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to registration
  • History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
  • Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
  • Known cardiac metastases
  • Known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible); patients with human immunodeficiency virus (HIV) are not eligible if on anti-retroviral medications
  • 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
  • Pregnant women or nursing mothers; women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception; if a female patient or a female partner of a patient becomes pregnant while the patient receives trametinib, the potential hazard to the fetus should be explained to the patient and partner (as applicable)
  • HIV-positive patients on combination antiretroviral therapy are ineligible
  • Patients who do not consent for PK studies to be performed (alternatively: patients who initially consent to be on study but withdraws consent for PK study will be taken off study and replaced)

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase 1 Study of Trametinib in Combination With Chemoradiation for KRAS Mutant Non-small Cell Lung Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum-tolerated dose (MTD) of GSK1120212 (trametinib) combined with standard chemoradiation in unresectable non-small cell lung cancer (NSCLC) and safety as measured by the rate of grade 3 or worse non-hematological toxicities occurring prior to the beginning of consolidation therapy (including all toxicities attributed to chemoradiation occurring within 10 weeks of the start of radiation therapy).

II. Pharmacokinetic (PK) analysis of carboplatin, paclitaxel, and trametinib.

SECONDARY OBJECTIVES:

  1. Response rate based on computed tomography (CT) or fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/CT imaging response assessment after completion of chemoradiation.

II. Biomarker correlate to response and resistance. III. Overall survival. IV. Patterns of recurrence. V. Determine dose delay and the percentage of dose delivered for each agent.

OUTLINE: This is a dose-escalation study of trametinib.

CONCURRENT CHEMOTHERAPY: Patients undergo intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) once daily (QD) 5 days a week for 6 weeks. Patients receive trametinib orally (PO) QD and carboplatin intravenously (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.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years.

Being tested
3-Dimensional Conformal Radiation Therapy, Carboplatin, Image Guided Radiation Therapy, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 3-Dimensional Conformal Radiation TherapyRadiation

    Also called 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT

    Undergo 3D-CRT

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • Image Guided Radiation TherapyRadiation

    Also called IGRT, image-guided radiation therapy, Image-Guided Radiotherapy

    Undergo IGRT

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Pharmacological StudyOther

    Correlative studies

  • TrametinibDrug

    Also called GSK1120212, JTP-74057, MEK Inhibitor GSK1120212

    Given PO

Study groups in NCT01912625
Study groupRoleWhat they receive
Treatment (trametinib, chemotherapy, radiation therapy)ExperimentalCONCURRENT 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Within 70 days from the start of radiation therapy

  2. Pharmacokinetic parameters of carboplatin and paclitaxel with the dosing of trametinib

    Measured: 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)

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

    Response rate will be estimated and 95% confidence interval will be provided.

    Measured: Up to 4 years

  2. Overall survival (OS)

    Unadjusted OS will be estimated by the Kaplan and Meier method.

    Measured: Up to 4 years

  3. Patterns of recurrence

    Relapse-free survival will be estimated by the Kaplan and Meier method.

    Measured: Up to 4 years

  4. KRAS mutation status

    KRAS and other biomarkers will be compared between pre-treatment tumors and recurrent tumors.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2013 (estimated)
  2. Study start28 Oct 2013
  3. Primary completion3 Nov 2017
  4. Study completion24 Feb 2023

Why it stopped: Inadequate accrual rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01912625
Sponsor's protocol ID
NCI-2013-01357
Other IDs
NCI-2013-01357, 2012-1053, 763093, 9448, 9448, P30CA016672, P50CA070907, U01CA062461
Status last verified
May 2023
First submitted
29 Jul 2013
Last updated
6 May 2023
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 3-Dimensional Conformal Radiation Therapy, Carboplatin and Image Guided Radiation Therapy in people with Recurrent Lung Non-Small Cell Carcinoma and Stage III Lung Non-Small Cell Cancer AJCC v7, run by National Cancer Institute (NCI) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Inadequate accrual rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Within 70 days from the start of radiation therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01912625.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023; AzTrials last refreshed its copy on 8 Nov 2026.

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