Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Disease Progression

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Treatment is started the day after registration (day 1)until progression according to Cheson international response criteria or documented toxicity.

Treatment will be administered orally once weekly, 2 hours before or after a meal, at day 1, 8, 15, 22 over a 28 day cycle period.

The starting dose level is 200 mg. 2 dose reduction are allowed (135 mg and 90 mg)in case of documented toxicity according to the specific algorithms.

MK2206

Hervé Ghesquières, MD

Philippe Cassier, MD

The purpose of this study is to evaluate the antitumor efficacy and the safety of MK 2206 in patients with relapsed or refractory diffuse large B cell lymphoma.

Diffuse Large B-cell Lymphoma (DLBCL) is the most frequent subtype of Non-Hodgkin lymphoma (NHL) around the world, in all age groups.

DLBCL is a curable disease and combination of monoclonal antibody against CD20 (rituximab) with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen have improved the prognosis of patients with a 20% increase of the cure rate. For the remaining patients who are not in complete response and/or who relapse after first line therapy, the possibility of cure is dramatically reduced.

As PI3K/AKT/mTOR pathway regulates the expression of cyclin D1, c-Myc and Stat3 proteins, which are involved in the pathogenesis of DLBCL HL), this signalling axis is an emerging therapeutic target for treatment of DLBCL.

One study has shown that the level of p-Akt is an adverse prognostic feature in DLBCL and is found in 52% of tumors samples from DLBCL patients.

Given the fact that AKT is overactivated in about to 52% of DLBCL and is considered as a poor prognosis factor, we postulate that targeting AKT in DLBCL may be an interesting therapeutic strategy.

MK-2206 is an orally selective allosteric inhibitor of AKT developed by MERCK currently highlighted as a promising therapeutic option for cancer patients and under clinical development in several Phase 1 trials.

Therefore, we propose to conduct a Phase II study using a two-stage Simon's design with objective response rate (ORR) as the primary endpoint.

Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

A Phase II Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

the objective response rate (ORR) is measured as per 2007 Cheson international response criteria.

safety profile is characterized by type, frequency and seriousness of the toxicities showed by patients and graded using CTCAE-V04.

the objective response rate (ORR) is measured as per 1999 Cheson international response criteria.

National Cancer Institute, France

Centre Leon Berard

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Gefitinib

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

Chih-Hsin Yang, MD, Ph.D

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.

Preclinical data from communication with Merck clinical and pre-clinical group support the application of MK2206 and an EGFR-TKI, and the synergistic effect of this combination. This proposed study is a phase I dose defining study to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib.

MK-2206 is a potent, orally active, allosteric inhibitor of human AKT1, AKT2, and AKT3 with preclinical anti-tumor activity.

This is a Phase I, single-center, open-label, non-randomized, dose-escalation study in patients with locally advanced or metastatic NSCLC. Patients who previously failed and progressed through EGFR inhibitor such as erlotinib or gefitinib and up to one line of chemotherapy will be enrolled into the study. Patients will be administered with oral MK-2206 and a standard dose of EGFR inhibitor gefitinib.

This study will be conducted in three cohorts to identify a recommended Phase II dose (RP2D) of MK-2206 in combination with standard dose of gefitinib (250 mg QD). Cohorts of 3 patients will be enrolled sequentially on escalating doses of MK-2206 administered in combination with a standard dose of gefitinib. Patients will advance doses of MK2206 if 0/3 patients or 0-1/6 develop DLT (Dose-Limiting Toxicity). If 1/3 patient develops DLT, the cohort will be expanded to 6. If 2/6 patients developed DLT, the dose will be de-escalate to 90 mg Qwk. The highest dose cohort with 0-1/6 with DLT will be deemed as MTD and used as cohort expansion for a total of 15 patients.

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

A Phase I Dose Defining Study For MK-2206 Combined With Gefitinib In NSCLC Population Enriched With EGFR Mutation

National Taiwan University Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma	NCT01466868	Diffuse Large B...	MK2206	18 Years - 90 Years	Centre Leon Berard
Dose Defining Study For MK-2206 Combined With Gefitinib In Non Small Cell Lung Cancer (NSCLC)	NCT01147211	Non Small Cell ...	MK2206	20 Years -	National Taiwan University Hospital

Spots Global Cancer Trial Database for mk2206

Every month we try and update this database with for mk2206 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mk2206

Every month we try and update this database with for mk2206 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mk2206 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.