Trial of MK-2206 + Endocrine Treatment in Patients With Hormone Receptor Positive Breast Cancer

NCT01240941 | Withdrawn Phase 2 DMC

• 1 other identifier: VICC BRE1029
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II Trial of MK-2206 in combination with Endocrine Therapy in patients with Hormone Receptor Breast Cancer. After the maximum tolerated dose is determined in the phase 1b trial (under a separate NCT number), efficacy will be evaluated among 17 patients.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy endpoint: Antitumor activity of MK-2206 when combined with exemestane +/- goserelin in pre- and post-menopausal patients with hormone receptor positive metastatic breast cancer, measured by clinical benefit rate.

  Clinical benefit rate is defined as complete response + partial response + stable disease for at least 24 weeks following initiation of treatment.

  24 weeks (6 cycles)

Secondary Outcomes (2)

• The safety and tolerability of MK-2206 given in combination with exemestane +/- goserelin in pre- and post-menopausal patients with hormone receptor positive metastatic breast cancer.

  every four weeks (1 cycle)

• Characterize the effect of MK-2206 in combination with exemestane +/- goserelin based on PI3K, AKT, and PTEN mutations

  tumor blocks to be obtained prior to beginning the trial

Study Arms (1)

MK-2206

EXPERIMENTAL

MK-2206 maximum tolerated dose found from Phase Ib trial (under a separate NCT number) taken orally on a weekly basis

Drug: MK-2206; Drug: Exemestane; Drug: Goserelin

Interventions

MK-2206 DRUG

dose to be determined on the Phase 1b trial (listed under a separate NCT number)

MK-2206

Exemestane DRUG

25 mg orally daily

MK-2206

Goserelin DRUG

3.6 mg orally monthly

MK-2206

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patient who has had chemotherapy, radiotherapy, or biological therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If the patient has residual toxicity from prior treatment,toxicity must be less than or equal to Grade 1.
• Patients must be at least 4 weeks post major surgical procedure, and all surgical wounds must be fully healed.
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1.
• 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 at least 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2)off steroids that are used to minimize surrounding brain edema.
• Patient has 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 clinically significant heart disease including:
• Clinically significant congestive heart failure, unstable angina pectoris,
• Clinically significant cardiac arrhythmia, history or current evidence of a myocardial infarction during the last 6 months,and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator.
• Baseline QTc prolongation greater than 450 msec (Bazett's Formula). Medications included in Arizona CERT Lists 1 and 2 (Appendix D) must be excluded. The concomitant use of drugs that are associated with increased risk for QT prolongation should be avoided in patients with congenital long QT syndrome (Appendix D, Arizona CERT List 3). Similarly, the concomitant use of drugs that are weakly associated with QT prolongation should be generally avoided (Appendix D, Arizona CERT List 4). Arizona CERT List 3 and 4 drugs should be used at the discretion of the Investigator and restricted where applicable. Any therapy given with these drugs should be used with caution, and patients receiving these medications should be carefully monitored.
• Patient with evidence of clinically significant bradycardia (heart rate less than 50 ), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2), or patients taking beta blockers, non-dihydropyridine calcium channel blockers, or digoxin.
• Patient with uncontrolled hypertension (i.e., 160/90 mHg SiBP). Patients who are controlled on antihypertensive medication will be allowed to enter the study.
• Patient at significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent diarrhea).
• Patient with poorly controlled diabetes defined as HbA1C greater than 8%.
• 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.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

MK 2206; exemestane; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Vandana Abramson, M.D.

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Medical Oncologist

Study Record Dates

• First Submitted: October 26, 2010
• First Posted: November 15, 2010
• Study Start: February 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 20, 2013

Record last verified: 2013-08