MK-2206+Endocrine Therapy in Patients With Hormone Receptor-Positive Breast Cancer

NCT01240928 | Withdrawn Phase 1 DMC

• 1 other identifier: VICC BRE 1029
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase Ib trial that evaluates 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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Tolerability of MK-2206 given in combination with exemestane +/- goserelin, as measured by maximum tolerated dose (MTD).

  The MTD will be defined as the highest dose tested in which a dose-limiting toxicity is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels.

  at 4 weeks

Secondary Outcomes (2)

• Number of participants with adverse events as a measure of safety of MK-2206 when combined with exemestane +/- goserelin

  At 4 weeks

• Characterize the effect of MK-2206 in combination with exemestane +/- goserelin based on PI3K, AKT, and PTEN mutations, as measured by immunohistochemistry and the SNaPshot assay.

  After collection of tumor tissue

Study Arms (1)

MK-2206 + exemestane +/- goserelin

EXPERIMENTAL

Oral MK-2206 and oral exemestane and subcutaneous goserelin (for pre-menopausal participants only)

Drug: MSK-2206; Drug: Exemestane; Drug: Goserelin

Interventions

MSK-2206 DRUG

Level 1: MK-2206 135mg weekly

MK-2206 + exemestane +/- goserelin

Exemestane DRUG

Level 1: Exemestane - 25mg daily

MK-2206 + exemestane +/- goserelin

Goserelin DRUG

Level 1: Goserelin- 3.6mg monthly for pre-menopausal subjects only

MK-2206 + exemestane +/- goserelin

Eligibility Criteria

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

You may qualify if:

• Clinical stage IV invasive mammary carcinoma, documented by histological analysis, ER-positive and/or PR-positive by immunohistochemistry (IHC), previous endocrine therapy in the metastatic setting or had metastatic recurrence within 6 months of adjuvant endocrine therapy. May have measurable or non-measurable disease, both are allowed. Any number of prior hormone or chemotherapy agents are acceptable
• Female and ≥ 18 years of age on the day of signing informed consent
• Performance status of 0 or 1 on the ECOG Performance Scale
• Adequate organ function as indicated by the following laboratory values:
• Hematological:
• Absolute neutrophil count (ANC) ≥ 1,500 /μL
• Platelets ≥ 100,000 /μL
• Hemoglobin ≥ 9 g/dL
• Renal:
• Serum creatinine or calculated creatinine clearance† - ≤ 1.5 x upper limit of normal (ULN) OR ≥60 mL/min for patients with creatinine levels \> 1.5 x institutional ULN
• Hepatic:
• Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 x ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤5 x ULN in patients with known liver metastasis
• Coagulation:
• Prothrombin time (PT)/INR ≤ 1.2 x ULN

You may not qualify if:

• Chemotherapy, radiotherapy, or biological therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If residual toxicity from prior treatment,toxicity must be ≤ Grade 1
• Must be at least 4 weeks post-major surgical procedure, and all surgical wounds must be fully healed
• Currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1
• 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 used to minimize surrounding brain edema
• Primary central nervous system tumor
• Known hypersensitivity to the components of study drug or its analogs
• History or current evidence of clinically significant heart disease including:
• congestive heart failure, unstable angina pectoris,
• 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 \> 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.
• Evidence of clinically significant bradycardia (HR \<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
• Uncontrolled hypertension (i.e., 160/90 mHg SiBP). Patients who are controlled on antihypertensive medication will be allowed to enter the study
• At significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent diarrhea)
• Poorly controlled diabetes defined as HbA1C \> 8%

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

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, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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
• Last Updated: August 20, 2013

Record last verified: 2013-08