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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Malignancies, Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: MGCD265+erlotinib; Drug: MGCD265+docetaxel

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Abramson Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MGCD265+erlotinib	Drug: MGCD265+erlotinib; MGCD265 and erlotinib administered daily
EXPERIMENTAL: MGCD265+docetaxel	Drug: MGCD265+docetaxel; MGCD265 administered daily; docetaxel administered once every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Investigators: Study Director: Vanessa Tassell, MethylGene Inc.

Publications and helpful links

General Publications

• Patnaik A, Gadgeel S, Papadopoulos KP, Rasco DW, Haas NB, Der-Torossian H, Faltaos D, Potvin D, Tassell V, Tawashi M, Chao R, O'Dwyer PJ. Phase I Study of Glesatinib (MGCD265) in Combination with Erlotinib or Docetaxel in Patients with Advanced Solid Tumors. Target Oncol. 2022 Mar;17(2):125-138. doi: 10.1007/s11523-022-00875-0. Epub 2022 Mar 28. Erratum In: Target Oncol. 2022 Apr 5;:

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (ESTIMATE): September 11, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): January 8, 2015
• Last Update Submitted That Met QC Criteria: January 6, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Docetaxel; Erlotinib Hydrochloride
• Other Study ID Numbers: 265-103