A Phase I Study of MK2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (2206-003 AM5)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00848718
First received: February 19, 2009
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to compare the safety and tolerability of several dose levels of MK-2206 in combination with chemotherapy and targeted therapy agents in participants with locally advanced or metastatic solid tumors.


Condition Intervention Phase
Locally Advanced, Metastatic Solid Tumors
Drug: MK-2206 combined with carboplatin + paclitaxel
Drug: MK-2206 combined with docetaxel
Drug: MK-2206 combined with erlotinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (One cycle = 21 days) ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose (MTD) of each of the three combinations [ Time Frame: Cycle 1 (One cycle = 21 days) ] [ Designated as safety issue: Yes ]
  • Maximum plasma concentration of MK-2206 (Cmax) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ] [ Designated as safety issue: No ]
  • Time to maximum plasma concentration of MK-2206 (Tmax) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ] [ Designated as safety issue: No ]
  • Minimum plasma concentration of MK-2206 (Ctrough) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ] [ Designated as safety issue: No ]
  • Area under the MK-2206 concentration versus time curve (AUC) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants who had a tumor response, according to standard RECIST (Response Evaluation Criteria in Solid Tumors) criteria [ Time Frame: Tumor assessments will be performed at baseline and on Day 1 of every other cycle of treatment (every 6 weeks) ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: March 2009
Study Completion Date: May 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-2206 + carboplatin + paclitaxel
MK-2206 combined with carboplatin and paclitaxel
Drug: MK-2206 combined with carboplatin + paclitaxel
MK-2206 given by mouth on days 1, 3, 5, and 7 of the 21 day cycle (30 mg, 45 mg, or 60 mg) OR MK-2206 given by mouth on Day 1 of the 21 day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg). On Day 1 of each 21 Day cycle, carboplatin + paclitaxel is given intravenously.
Other Name: Paraplatin, Taxol
Experimental: MK-2206 + docetaxel
MK-2206 combined with docetaxel
Drug: MK-2206 combined with docetaxel
MK-2206 given by mouth on days 1, 3, 5, and 7 of the 21 day cycle (either 45 mg or 60 mg) (this dosing schedule is no longer enrolling). MK-2206 given by mouth on Day 1 of the 21 day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg). On day 1 of each 21 day cycle, docetaxel is given intravenously. In this treatment arm, an oral corticosteroid is to be taken by mouth every day.
Other Name: Taxotere
Experimental: MK-2206 + erlotinib
MK-2206 combined with erlotinib
Drug: MK-2206 combined with erlotinib
MK-2206 given by mouth every other day (30 mg, 45 mg or 60 mg) OR MK-2206 given by mouth on Days 1, 8, and 15 of the 21 day cycle (90 mg, 135 mg, or 200 mg). In addition, erlotinib is given daily by mouth in a continuous 21 day cycle for the duration of the study.
Other Name: Tarceva

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria :

  • Participants must have locally advanced or metastatic solid tumors.
  • Participant is male or female greater than or equal to 18 years of age.
  • Participant must have a performance status less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Female participants of childbearing potential has a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
  • Participants in the MK-2206 + carboplatin/paclitaxel and MK-2206 + docetaxel treatment arms will be limited to no more than 3 prior cytotoxic therapies for metastatic or recurrent diseases.
  • Participant is able to swallow capsules and has no surgical or anatomical condition that will prevent the Participant from swallowing.

Exclusion Criteria:

  • Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks.
  • Participants must be least 4 weeks post-surgery and do not expect major surgery in the study duration.
  • Participant is currently participating or has participated in a study with an investigational compound or device within 30 days.
  • Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Participant with a primary central nervous system tumor.
  • Participant has known hypersensitivity to the components of study drug.
  • Participant has a history or current evidence of heart disease.
  • Participant has evidence of clinically significant bradycardia (slow heart rate).
  • Participant has uncontrolled high blood pressure.
  • Participant at significant risk for hypokalemia (low potassium levels).
  • Participant is a known diabetic
  • Participant has known psychiatric or substance abuse disorders.
  • Participant is a user of illicit drugs.
  • Participant is pregnant or breastfeeding.
  • Participant is Human Immunodeficiency Virus (HIV) positive.
  • Participant has known history of Hepatitis B or C or active Hepatitis A.
  • Participant has symptomatic ascites or pleural effusion.
  • Participant is receiving treatment with oral corticosteroids.
  • Participant is using a potent cytochrome P(450) 3A4 (CYP3A4) inhibitor or inducer.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00848718     History of Changes
Other Study ID Numbers: 2009_547, MK-2206-003
Study First Received: February 19, 2009
Last Updated: May 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Tumors, cancer

Additional relevant MeSH terms:
Neoplasms
Docetaxel
Carboplatin
Paclitaxel
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014