Dose Defining Study For MK-2206 Combined With Gefitinib In Non Small Cell Lung Cancer (NSCLC)

NCT01147211 | Unknown Phase 1

• 1 other identifier: 201001017M
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study of MK2206 (an AKT inhibitor)and gefitinib in nonsmall cell lung cancer patients who failed prior chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). The patient population is enriched for EGFR mutations. The purpose of this study is to determine whether it is safe to administered MK-2206 in combination with gefitinib in adult patients with locally advanced or metastatic non-small cell lung cancer. The second purpose of this study is to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib. A standard 3-3 dose escalation scheme of MK-2206 with fix dose gefitinib is used in this study.

Conditions

Non Small Cell Lung Cancer

Keywords

dose defining; MK-2206; NSCLC With EGFR Mutation; NSCLC

Outcome Measures

Primary Outcomes (1)

• to provide safety assessment and define dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of MK-2206 in combination with gefitinib in NSCLC

  21 days

Secondary Outcomes (1)

• To explore the anti-tumor activity and to assess the pharmacokinetic profile of MK-2206 in combination with gefitinib.

  21 days

Study Arms (1)

MK2206 in combination with Gefitinib

EXPERIMENTAL

MK-2206 will be administered orally in a starting dose level of 135 mg on a schedule of Qwk in repeating 3-week treatment cycles in combination with gefitinib in continuous 21-day cycles for the duration of the study

Drug: MK2206

Interventions

MK2206 DRUG

MK-2206 will be administered orally in a starting dose level of 135 mg on a schedule of Qwk in repeating 3-week treatment cycles in combination with gefitinib in continuous 21-day cycles for the duration of the study

MK2206 in combination with Gefitinib

Eligibility Criteria

• Age: 20 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 locally advanced or metastatic NSCLC who have received EGFR inhibitors (such as gefitinib, erlotinib) for at least 3 months and progressed and also received at least one line of platinum-based chemotherapy. In the MTD expansion cohort, patients must have documented progression on gefitinib, erlotinib, afatinib(BIBW2992) or PF299804 within 4 weeks of starting gefitinib and MK2206 treatment. There should be no anticancer treatment between above mentioned treatment and protocol treatment.
• Patient is male or female and ≥ 20 years of age on the day of signing informed consent.
• Patient must have performance status ≤ 2 on the ECOG Performance Scale.
• Patient must have adequate organ function
• Female patient of childbearing potential has a negative serum or urine pregnancy test β-hCG within 72 hours prior to receiving the first dose of study medication.
• Patient have completed any targeted therapy (excluding gefitinib, erlotinib or any small molecule EGFR tyrosine kinase inhibitors ), any chemotherapy regimens and therapeutic radiation for a minimum of 30 days prior to starting of treatment, and palliative radiotherapy covering less than 30% bone marrow for a minimum 14 days prior to starting of treatment.
• Prior usage of BIBW2992 are allowed if patient failed on BIBW2992 over 3-month therapy.
• Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
• Patient is able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.

You may not qualify if:

• Patient who has had chemotherapy, radiotherapy, biological therapy, or BIBW2992 (except gefitinib, erlotinib) within 30 days (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or 5x half-life, whichever is longer, prior to starting of treatment, or who has not recovered from the adverse events due to previous agents administered more than 30 days prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
• Patients who has had major surgery within 4 weeks prior to starting of treatment or expect major surgery in the study duration.
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5x half-life from prior agents, whichever is longer, of Day 1 of this study.
• Patient has known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids.
• Patient with a primary central nervous system tumor.
• Patient has known hypersensitivity to the components of study drug or its analogs.
• Patient has a history or current evidence of heart disease.
• Patient with evidence of clinically significant bradycardia (HR \< 50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2), or patients taking non-dihydropyridine calcium channel blockers, or digoxin.
• Patient with uncontrolled hypertension (i.e. ≥160/90 mHg). Patients who are controlled on antihypertensive medication will be allowed to enter the study.
• Patient at significant risk for hypokalemia (eg. patients on high dose diuretics, or with recurrent diarrhea)
• Patient is a known diabetic patient
• Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
• Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

MK 2206

Condition Hierarchy (Ancestors)

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

Study Officials

• Chih-Hsin Yang, MD, Ph.D

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: June 22, 2010
• Study Start: September 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 3, 2013

Record last verified: 2013-04

Locations

TW (1)