MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

NCT01319539 | Terminated Phase 2 Results

• 6 other identifiers: NCI-2011-02513CDR0000696821AECM-AAAF39128740N01CM62204P30CA013330
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial is studies how well Akt inhibitor MK2206 works in treating patients with stage I-III breast cancer that can be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Change in pAKT Levels

  This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).

  Baseline, 2 weeks (Day 0 - surgery)

Secondary Outcomes (2)

• Change in pS6 Levels

  Baseline, 2 weeks (Day 0 - surgery)

• Change in Ki-67 Expression

  Baseline, 2 weeks (Day 0 - surgery)

Study Arms (1)

Treatment (Akt inhibitor MK2206)

EXPERIMENTAL

Patients receive Akt inhibitor MK2206 PO on days -9 and -2, and undergo segmental resection or total mastectomy (therapeutic conventional surgery) on day 0. Patient samples will be processed for pharmacological study and laboratory biomarker analysis.

Drug: Akt Inhibitor MK2206; Procedure: Therapeutic Conventional Surgery; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

Interventions

Akt Inhibitor MK2206 DRUG

Given PO

Also known as: MK2206

Treatment (Akt inhibitor MK2206)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (Akt inhibitor MK2206)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (Akt inhibitor MK2206)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Akt inhibitor MK2206)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically-confirmed operable invasive breast cancer and have undergone core needle biopsy with an anticipated surgical resection for residual disease after enrollment
• Patients must have clinical stage I-III invasive breast (invasive tumor must be clinically at least \>= T1c by radiograph or palpation)
• Patients must have available tissue from core biopsies for biomarker assessment; it is recommended that at least 4 cores be performed with 12 gauge (or smaller gauge) needles; this includes cores underneath ultrasound-guidance
• Patients are planning to undergo surgical treatment with either segmental resection or total mastectomy (required: 2 doses of weekly MK-2206 prior to surgery; the first dose will be at day -9 \[+/- 1 day\] and second dose at day -2 \[+/- 1 day\] in relation to surgery \[day 0\])
• Patients may have a history of contralateral breast cancer, provided there is no evidence of recurrence of the initial primary breast cancer
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky \>= 80%)
• Leukocytes \>= 3,000/ul within 28 days of registration
• Platelets \>= 100,000 /uL within 28 days of registration
• Hemoglobin (Hgb) \>= 9 g/dL within 28 days of registration
• Creatinine =\< 1.5 x upper limit of normal (ULN) within 28 days of registration
• Prothrombin time (PT), partial thromboplastin time (PTT) =\< 1.2 x ULN within 28 days of registration
• Total bilirubin =\< 1.5 x ULN within 28 days of registration
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN within 28 days of registration
• Patients of childbearing potential must have a negative serum or urine pregnancy test beta-human chorionic gonadotropin (β-hCG) within 72 hours prior to receiving the first dose of study medication
• Women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately

You may not qualify if:

• Patients may not have any known evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases) or locally recurrent breast cancer
• Patients with inflammatory breast cancer are not eligible
• Patients with prior chemotherapy or radiation therapy within 6 months of study entry are not eligible (i.e. patient who have received neoadjuvant therapy are not eligible)
• Patients may not be receiving any other investigational agents, including other inhibitors of PI3K, Akt, or mammalian target of rapamycin (mTOR)
• Men diagnosed with breast cancer
• Patients may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 used in the study
• Patients with known diabetes which is poorly controlled diabetes (hemoglobin A1c \[HBA1C\] \>= 8%) should be excluded; if patient is taking metformin, must have been taking this medication for \> 3 months, as metformin is thought to impact PI3K/Akt signaling
• Baseline corrected QT interval (QTc) \> 470 msec will exclude patients from entry on study; patients with a baseline bundle branch block will be excluded
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK2206
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467-2490, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

MK 2206

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Kevin Kalinsky, MD
• Organization: Columbia University Medical Center

kk2693@cumc.columbia.edu

212-305-1945

Study Officials

• Kevin Kalinsky

  Montefiore Medical Center - Moses Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2011
• First Posted: March 21, 2011
• Study Start: April 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: August 30, 2017
• Results First Posted: August 1, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)