Akt Inhibitor MK2206 in Combination With Lapatinib Ditosylate in Patients With Advanced or Metastatic Solid Tumors or Breast Cancer

NCT01245205 | Completed Phase 1

• 7 other identifiers: NCI-2011-02550WCCC-CO-10904CDR0000688912CO109048709P30CA014520U01CA062491
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and the best dose of Akt inhibitor MK2206 and lapatinib ditosylate in treating patients with solid tumors or breast cancer that has spread to other places in the body. Akt inhibitor MK2206 and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• MTD of Akt inhibitor MK-2206 and lapatinib ditosylate, defined as the dose level at which less than one-third of patients experience a DLT as graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4 (Part I)

  35 days

• Incidence of adverse reactions to Akt inhibitor MK2206 and lapatinib ditosylate in patients with advanced and unresectable or metastatic HER2+ breast cancer previously treated with trastuzumab as assessed by NCI CTCAE v. 4 (Part II)

  Possible adverse events will be reported in tabular format.

  Up to 4 years

Secondary Outcomes (10)

• Response rate (complete or partial response or stable disease) measured by Response Evaluation Criteria in Solid Tumors (RECIST) (Part I)

  Up to 4 weeks

• Incidence of DLTs assessed by NCI CTCAE v. 4 (Part I)

  Up to 4 weeks

• Incidence of adverse events, graded using NCI CTCAE v. 4 (Part I)

  Up to 4 weeks

• Response rates using RECIST guidelines (Part II)

  Up to 4 years

• Disease progression using RECIST guidelines (Part II)

  Up to 4 years

Study Arms (1)

Treatment (Akt inhibitor MK2206 and lapatinib ditosylate)

EXPERIMENTAL

Patients receive Akt inhibitor MK2206 PO QOD for 28 days (35 days for course 1) and lapatinib ditosylate PO QD or BID on days 1-28 (days 9-35 for course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Akt inhibitor MK2206; Drug: lapatinib ditosylate; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

Akt inhibitor MK2206 DRUG

Given PO

Also known as: MK2206

Treatment (Akt inhibitor MK2206 and lapatinib ditosylate)

lapatinib ditosylate DRUG

Given PO

Also known as: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb

Treatment (Akt inhibitor MK2206 and lapatinib ditosylate)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (Akt inhibitor MK2206 and lapatinib ditosylate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (Akt inhibitor MK2206 and lapatinib ditosylate)

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically or cytologically confirmed advanced or metastatic solid tumor for which no standard curative measure exists
• Patients must have either evaluable or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• Patients may have previously had disease progression on lapatinib, but should not have demonstrated prior serious or life-threatening intolerance to doses of lapatinib exceeding 1000 mg per day
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< upper limit of normal (ULN); in the case of a patient with known Gilbert's disease, s/he will be eligible as long as total serum bilirubin is less than 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 times upper limit of normal
• Creatinine =\< ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 by Cockcroft-Gault for patients with creatinine levels above institutional normal
• Patients with treated, stable brain metastases are allowed to enroll; patients must be at least 4 weeks from radiation and off any medications used to treat brain metastases; patients are allowed to be on anti-epileptic medications that are not metabolized by cytochrome P450; patients with brain metastases must have stable brain imaging within 4 weeks prior to starting study
• Patients with progressive brain metastases who are not candidates for further local therapy (e.g. more radiation or surgery) but who have clinically asymptomatic brain are also eligible to enroll, as long as predicted life expectancy with the brain metastases meets or exceeds study requirements
• Women of childbearing potential and men should use contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation AS WELL AS for one month after stopping use of the study agents
• 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 who have had chemotherapy, therapy with trastuzumab, bevacizumab or other targeted therapy, or radiotherapy within 4 weeks (6 weeks for regimens including carmustine \[BCNU\], nitrosoureas or mitomycin C) prior to entering the study; the following will apply with regards to endocrine therapy:
• Patients receiving an aromatase inhibitor (AI) are eligible as long as they stop the AI one day prior to beginning study agents
• Patients receiving tamoxifen or fulvestrant should have received their last dose at least 2 weeks prior to beginning study agents
• Patients who have not recovered (=\< grade 1) from adverse events due to agents administered more than 4 weeks earlier (tolerable grade 2 adverse events may be allowed at the discretion of the investigator)
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206, lapatinib or other agents used in the study
• Patients receiving any medications or substances that are strong or moderate inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP 450 3A4) are ineligible unless they can be transitioned off this medication prior to study drug initiation
• Patients on strong or moderate inhibitors/inducers will become eligible if they discontinue all such medications at least 5 days prior to start of therapy and no further doses are anticipated for the duration of investigational therapy
• In order to be considered a contraindicated medication, a patient must be taking the drug systemically and on a regular and scheduled basis; for example, a topical medication taken intermittently need not be stopped
• Patients currently taking weak CYP3A4 inducers, and/or inhibitors are eligible
• Patients currently taking sensitive substrates with narrow therapeutic indices are ineligible unless:
• The medication can be monitored clinically in the opinion of the principal investigator (PI)/Study Chair; monitoring will be performed on a schedule to be determined by the PI/study chair and treating physician (MD); for example, a substrate medication that can be clinically monitored is digoxin
• If the medication CANNOT be monitored clinically, they discontinue all such medications at least 5 days prior to start of therapy and no further doses are anticipated for the duration of investigational therapy
• Patients with diabetes or at risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled before the patient enters the trial
• Inadequately controlled diabetes mellitus or hyperglycemia will be defined as:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Sanford Cancer Center-Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

MK 2206; Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Amye Tevaarwerk

  University of Wisconsin, Madison

  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: November 19, 2010
• First Posted: November 22, 2010
• Study Start: November 1, 2010
• Primary Completion: August 1, 2014
• Last Updated: October 23, 2014

Record last verified: 2014-10

Locations

US (2)