MK2206 and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Metastatic Breast Cancer

NCT01263145 | Completed Phase 1

• 7 other identifiers: NCI-2011-025622010-0245CDR00006907238739P30CA016672U01CA062461U01CA062490
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of Akt inhibitor MK2206 (MK2206) when given together with paclitaxel and to see how well they work in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment or breast cancer that has spread to other places in the body. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Akt inhibitor MK2206 and paclitaxel may be a better treatment for solid tumors or breast cancer.

Conditions

Adult Solid Neoplasm; Recurrent Breast Carcinoma; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Antitumor activity of the combination in metastatic breast cancer (Expansion phase)

  Up to 3 weeks after completion of study treatment

• MTD of the combination of MK-2206 and paclitaxel defined as the dose level in which less than or equal to 1 out of 6 patients develop dose limiting toxicity assessed using Common Terminology Criteria for Adverse Events version 4 (Phase I)

  21 days

Secondary Outcomes (7)

• Change in average number of circulating tumor cells (CTCs)

  Baseline to up to 2 weeks

• Change in multiplex proteomics

  Baseline to up to day 17

• Change in percentage of biomarkers assessed using immunohistochemistry

  Baseline to up to 2 weeks

• Change in percentage of marker of proliferation Ki-67 (Ki-67) positive cells

  Baseline to up to 2 weeks

• Change in reverse phase proteomic arrays (RPPA)

  Baseline to up to day 8

Other Outcomes (3)

• Change in expression of plasma markers

  Baseline to up to day 17

• PIK3CA mutation status

  Up to day 17

• Prevalence of single nucleotide polymorphisms (SNPs) in PI3K pathway genes

  Up to day 17

Study Arms (1)

Treatment (Akt inhibitor MK2206 and paclitaxel)

EXPERIMENTAL

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and Akt inhibitor MK2206 PO QD on days 2, 9, and 16. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Akt Inhibitor MK2206; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study

Interventions

Akt Inhibitor MK2206 DRUG

Given PO

Treatment (Akt inhibitor MK2206 and paclitaxel)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Akt inhibitor MK2206 and paclitaxel)

Paclitaxel DRUG

Given IV

Treatment (Akt inhibitor MK2206 and paclitaxel)

Pharmacological Study OTHER

Correlative studies

Treatment (Akt inhibitor MK2206 and paclitaxel)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have received at least two lines of therapy; for the expansion phase: female patients with metastatic breast cancer who have received a maximum of three lines of therapy
• Absolute neutrophil count (ANC) \>= 1,000/uL
• Platelets \>= 100,000/uL
• Hemoglobin (Hgb) \>= 9 g/dL
• Creatinine =\< 1.5 x upper limit of normal (ULN)
• Prothrombin time (PT) within institutional guideline for biopsy procedure
• Total bilirubin =\< 1.5 x ULN
• Alanine aminotransferase (ALT) =\< 2.5 x ULN (=\< 3 x ULN for subjects with liver involvement with cancer)
• A known diabetic patient who is taking insulin or oral anti-diabetic therapy must have a hemoglobin A1C (HBA1C) =\< 8% or a fasting serum glucose =\< 110% ULN
• Patient will have a tumor suitable for fine-needle aspirates (FNA) and core biopsy for research purposes (determined by the treating physician)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) or evaluable disease (e.g., bone metastasis or lesions which do not fulfill RECIST criteria for metastatic disease)
• Patients with central nervous system (CNS) metastasis who have completed a course of therapy (for treatment of CNS metastasis) would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as:
• No evidence of new or enlarging CNS metastasis
• Off steroids and anticonvulsants

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Patients taking a potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitor or inducer will be excluded; patients who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is longer) prior to the first dose MK-2206
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bradycardia, related to cardiac disease, bundle branch block, 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

MK 2206; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Funda Meric-Bernstam

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: December 20, 2010
• Study Start: January 5, 2011
• Primary Completion: October 19, 2012
• Study Completion: October 19, 2012
• Last Updated: August 25, 2017

Record last verified: 2017-08

Locations

US (3)