Safety and Tolerability of Trametinib in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer

NCT01938456 | Withdrawn Phase 1

• 1 other identifier: 117132
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of the combination therapy of trametinib and docetaxel with growth factor support in Japanese subjects with Stage IV or a postoperative recurrence non-small cell lung cancer (NSCLC). This study data will be used for making decision for further Japanese development plan for NSCLC. Six evaluable subjects will be enrolled in a dose level to evaluate the safety and tolerability of the combination treatment. Dose-limiting toxicity will be assessed during the first 21 days of combination therapy.

Conditions

Lung Cancer, Non-Small Cell

Keywords

Non-small cell lung cancer; GSK1120212 (trametinib); Japanese; Phase Ib; combination therapy; docetaxel; MEK inhibitor

Outcome Measures

Primary Outcomes (3)

• Change from baseline in laboratory parameter values.

  Laboratory parameters include: hematology, clinical chemistry, coagulation tests and urinalysis tests.

  Baseline and up to 6 months

• Change from baseline in vital sign values

  Vital sing measurement include: temperature, systolic blood pressure, diastolic blood pressure, heart rate, and blood oxygen saturation (SpO2)

  Baseline and up to 6 months

• Number of participants with Adverse events (AEs).

  AEs will be collected from the time the first dose of study treatment is administered until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice

  Baseline and up to 6 months

Secondary Outcomes (3)

• Composite of pharmacokinetic (PK) parameters for

  PK samples will be collected at pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 24 hours (pre-dose) post-dose/infusion start

• Composite of PK parameters for Docetaxel

  PK samples will be collected at pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 24 hours (pre-dose) post-dose/infusion start

• Tumor response as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

  6 months

Study Arms (1)

Trametinib + Docetaxel + Filgrastim

EXPERIMENTAL

Participants will receive Trametinib once daily for 21 days of each cycle + Intravenous Docetaxel once every three weeks over at least a one-hour infusion + Filgrastim (growth factor) subcutaneous injection once daily for prophylactic use.

Drug: Trametinib; Drug: Docetaxel; Drug: Filgrastim

Interventions

Trametinib DRUG

Biconvex film coated oral tablets for once daily use with unit dosage strength of 0.5mg and 2.0 mg for dose level of 2.0mg, 1.5mg, 1.0mg, and 0.5mg

Trametinib + Docetaxel + Filgrastim

Docetaxel DRUG

Yellow or brownish yellow solution for injections with unit dosage strength of 20mg and 80 mg for intravenous infusion once every 3 weeks over at least one-hour infusion

Trametinib + Docetaxel + Filgrastim

Filgrastim DRUG

Clear and colorless solution for once daily sub-cutaneous injection with unit dosage strength of 75 micrograms (mcg) for dose level of 50 mcg/meter\^2 or 75 mcg/body

Trametinib + Docetaxel + Filgrastim

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects eligible for enrolment in the study must meet all of the following criteria:
• Provided signed written informed consent.
• years old or older (at the time consent is obtained).
• Histologically or cytologically confirmed NSCLC.
• Diagnosed of Stage IV, or postoperative recurrence.
• Tumor progression after receiving one prior platinum-based chemotherapy. Targeted therapies (gefitinib, crizotinib, etc) with no significant hematological toxicities will not be counted.
• Performance status score of ≤1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• 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.
• All prior treatment-related toxicities must be CTCAE v4.0 \<=Grade 1 (except alopecia) at the time of enrollment.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective contraception throughout the treatment period, and for 4 months after the last dose of study treatment.
• Men must agree to use effective contraception throughout the treatment period of docetaxel.
• Adequate organ baseline function defined as Hematology: absolute neutrophil count\>=1.5 x 10\^9/Liter (L), hemoglobine\>=9 gramms/decilitre, platelet\>==100 x 10\^9/L, Prothrombine time/international normalized ratio and activated partial thromboplastine time\<=1.5 x upper limit of normal (ULN) Hepatic: albumin\>=2.5 grams/decilitre, total bilirubine \<=ULN, aspartate aminotransferase and alanine aminotransferase \<=1.5 x ULN if alkaline phosphatase is \>=ULN or \<=2.5 ULN if alkaline phosphatase is \<ULN.
• Renal: creatinine\<=1.5 x ULN or calculated creatinine clearance \>=50 millilter (mL)/minute.
• Cardiac:left ventricular ejector factor\>=lower limit of normal by echocardiogram.
• Negative for Hepatitis B surface (HBs) antigen, Hepatitis virus B core (HBc) antibody, HBs antibody and Hepatitis C Virus (HCV) antibody. If HBs antigen is negative and both or either of HBc and HBs antibody is positive, Hepatitis B Virus (HBV) DNA should be measured.

You may not qualify if:

• Anti-cancer therapy (including chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, major surgery, tumor embolization or investigational therapy) within the last three weeks, with the following exceptions: six weeks for prior nitrosourea or mitomycin C and two weeks for anti-cancer therapy given continuously or on a weekly basis with limited potential for delayed toxicity.
• Previously treated with docetaxel
• Previously treated with MEK inhibitor
• Current use of a prohibited medication
• Suspected of or currently have clinically significant infectious disease.
• Hypersensitivity to polysorbate 80.
• Hypersensitivity to filgrastim or growth factor
• History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
• History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes) Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR such as: Evidence of new optic disc cupping, Evidence of new visual field defects on automated perimetry, Intraocular pressure \>21 millimeter of mercury (mmHg) as measured by tonography.
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Subjects who require treatment for these conditions should be excluded.
• History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or in situ carcinoma are eligible.
• Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
• History of interstitial lung disease or pneumonitis
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, metabolic, or cardiac disease).
• History or evidence of cardiovascular risk including any of the following:

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

trametinib; Docetaxel; Filgrastim

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: October 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: July 28, 2014

Record last verified: 2014-07