A Study of MGCD265 Given With Erlotinib or Docetaxel in Subjects With Advanced Malignancies or Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to assess the safety profile of MGCD265 when administered in combination with the marketed anticancer drugs erlotinib and docetaxel.

Official Title
-----------------
A Phase I/II Study of MGCD265 in Combination With Erlotinib or Docetaxel in Subjects With Advanced Malignancies and in Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
-----------------
Advanced Malignancies, Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: MGCD265+erlotinib
* Drug: MGCD265+docetaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Part 1: Patients with advanced metastatic or unresectable solid malignancy that is refractory to standard therapy and/or existing therapies. Evaluable disease. Documented progressive disease during or following most recent treatment regimen. Adequate hepatic parameters. Age ≥18 years. Life expectancy greater than 3 months. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate renal function. Adequate bone marrow function. Capable of understanding and complying with the protocol and written informed consent. Negative pregnancy test for women of childbearing potential. Use of adequate contraception as needed. Subjects consenting to optional fresh biopsies, must not require concurrent anticoagulation medication. Part 2: Histologically or cytologically confirmed advanced Stage 3b or 4 NSCLC. Measurable disease per RECIST. At least one prior chemotherapy regimen for advanced disease. No prior erlotinib or docetaxel therapy. Documented progressive disease during or following most recent treatment regimen. Adequate hepatic parameters. Age ≥18 years. Life expectancy greater than 3 months. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate renal function. Adequate bone marrow function. Capable of understanding and complying with the protocol and written informed consent. Negative pregnancy test for women of childbearing potential. Use of adequate contraception as needed. Exclusion Criteria: Recent anticancer treatment. Prior treatment with an investigational cmet inhibitor or HCF inhibitor or antibody. Uncontrolled concurrent illness. History of bleeding diathesis or coagulopathy. History of stroke or transient ischemic attack. History of a cardiovascular illness. QT interval corrected for heart rate (QTc) >470 msec. Left ventricular ejection fraction (LVEF) <50%. Immunocompromised subjects. Lack of recovery to grade ≤1 from significant adverse events due to antineoplastic agents, investigational drugs, or other medications administered prior to study enrollment. Symptomatic or uncontrolled brain metastases requiring current treatment. Active gastrointestinal conditions or a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. History of other malignancy treated with curative intent within the 5 previous years. Lung tumor lesions with increased likelihood of bleeding. History of major surgery within 28 days of first receipt of study drug. History of autologous bone marrow transplant (BMT) within the previous five years, or subjects with organ transplants or allogeneic BMT. Nursing or pregnant women; female subjects of childbearing potential must have a negative pregnancy test at screening. Unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs. Any other condition or finding that in the opinion of the Investigator or Medical Monitor may render the subject at excessive risk for treatment complications or may render difficult the evaluation of treatment response. Allergy or hypersensitivity to components of either the MGCD265, erlotinib or docetaxel formulations (depending on the group that the subject is assigned to).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGCD265+erlotinib<br> | Drug: MGCD265+erlotinib<br>* MGCD265 and erlotinib administered daily<br>|
| Experimental: MGCD265+docetaxel<br> | Drug: MGCD265+docetaxel<br>* MGCD265 administered daily; docetaxel administered once every 3 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Safety profile (including maximum tolerated dose and dose limiting toxicities) |  | 1 year | 
| Phase II: Antitumor activity of MGCD265+erlotinib and MGCD265+docetaxel |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Pharmacokinetic profiles of MGCD265+erlotinib and MGCD265+docetaxel |  | 2 months | 
| Phase I and Phase II: Pharmacodynamic profiles of MGCD265+erlotinib and MGCD265+docetaxel |  | 1 year | 
| Phase I: Antitumor activity of MGCD265+erlotinib and MGCD265+docetaxel. |  | 1 year | 
| Phase II: Safety profile of MGCD265+erlotinib and MGCD265+docetaxel; |  | 1 year |