Clinical Trials /

Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

NCT01802320

Description:

This phase II trial studies how well v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor MK2206 works in treating patients with previously treated colon or rectal cancer that has spread from the primary site to other places in the body or nearby tissue or lymph nodes and cannot be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Akt Inhibitor MK2206</span> in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

Title

  • Brief Title: Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery
  • Official Title: A Phase 2 Study of MK-2206 in Previously Treated Metastatic Colorectal Cancer Patients Enriched for PTEN Loss and PIK3CA Mutation
  • Clinical Trial IDs

    NCT ID: NCT01802320

    ORG ID: NCI-2013-00487

    NCI ID: NCI-2013-00487

    Trial Conditions

    Colon Mucinous Adenocarcinoma

    Colon Signet Ring Cell Adenocarcinoma

    Rectal Mucinous Adenocarcinoma

    Rectal Signet Ring Cell Adenocarcinoma

    Recurrent Colon Carcinoma

    Recurrent Rectal Carcinoma

    Stage IIIA Colon Cancer

    Stage IIIA Rectal Cancer

    Stage IIIB Colon Cancer

    Stage IIIB Rectal Cancer

    Stage IIIC Colon Cancer

    Stage IIIC Rectal Cancer

    Stage IVA Colon Cancer

    Stage IVA Rectal Cancer

    Stage IVB Colon Cancer

    Stage IVB Rectal Cancer

    Trial Interventions

    Drug Synonyms Arms
    Akt Inhibitor MK2206 Akt inhibitor MK2206, MK2206 Treatment (Akt inhibitor MK2206)

    Trial Purpose

    This phase II trial studies how well v-akt murine thymoma viral oncogene homolog 1 (Akt)
    inhibitor MK2206 works in treating patients with previously treated colon or rectal cancer
    that has spread from the primary site to other places in the body or nearby tissue or lymph
    nodes and cannot be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor
    cells by blocking some of the enzymes needed for cell growth.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the response rate to MK-2206 (Akt inhibitor MK2206), defined as complete
    response (CR) + partial response (PR).

    SECONDARY OBJECTIVES:

    I. To determine response rate to MK-2206 in patients with phosphatase and tensin homolog
    (PTEN) loss or phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
    (PIK3CA) mutation in a pretreatment biopsy from a metastatic site.

    II. To determine progression-free survival (PFS) and overall survival (OS). III. To
    determine the time to treatment failure (TTF), and duration of tumor response (DR).

    IV. To determine the safety profile and tolerability of this regimen in this patient
    population.

    V. To determine effect of PTEN, v-raf murine sarcoma viral oncogene homolog B1 (BRAF),
    PIK3CA, and AKT mutations and semi-quantitative grading of PTEN expression on clinical
    response.

    OUTLINE:

    Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22. Treatment
    repeats every 28 days for up to 24 months in the absence of disease progression or
    unacceptable toxicity.

    After completion of study treatment, patients are followed up every 6 months.

    Trial Arms

    Name Type Description Interventions
    Treatment (Akt inhibitor MK2206) Experimental Patients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Akt Inhibitor MK2206

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have histologically confirmed, radiologically measurable metastatic or
    locally advanced unresectable colorectal adenocarcinoma that is amenable to
    image-guided biopsy; disease in previously radiated regions may not be considered
    measurable unless there has been demonstrated progression in the lesion

    - Patients must have progressed on or been intolerant to a fluoropyrimidine-based
    chemotherapy regimen; there is no limit on the number of prior treatment regimens
    permitted

    - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

    - Life expectancy of greater than 12 weeks

    - Leukocytes >= 3,000/mcL

    - Absolute neutrophil count >= 1,500/mcL

    - Platelets >= 100,000/mcL

    - Total bilirubin =< institution upper limit of normal

    - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<
    2.5 X institutional upper limit of normal or =< 5 X institutional upper limit of
    normal for patients with known liver metastasis

    - Creatinine =< institution upper limit of normal OR creatinine clearance >= 60
    mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

    - Women of child-bearing potential and men must agree to use adequate contraception
    (double barrier method of birth control; abstinence) prior to study entry, for the
    duration of study participation, and 4 months after completion of MK-2206
    administration; should a woman become pregnant or suspect she is pregnant while she
    or her partner is participating in this study, she should inform her treating
    physician immediately; men treated or enrolled on this protocol must also agree to
    use adequate contraception prior to the study, for the duration of study
    participation, and 4 months after completion of MK-2206 administration

    - Patients must be able to swallow whole tablets; nasogastric or gastrostomy (G) tube
    administration is not allowed; tablets must not be crushed or chewed

    - Ability to understand and the willingness to sign a written informed consent document

    - Tumor must be wild type for the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
    (KRAS) and BRAF oncogenes, and must have known PIK3CA, AKT mutation status and PTEN
    expression status

    Exclusion Criteria:

    - Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
    nitrosoureas or mitomycin C) prior to entering the study; if the patient has residual
    toxicity from prior treatment, toxicity must be =< grade 1 (or =< grade 2 for
    peripheral neuropathy and/or alopecia)

    - Patients who are receiving or have received any other investigational agents within
    30 days of study day 1, or who have previously received MK-2206 at any time

    - Patient has known active central nervous system (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:

    - No evidence of new or enlarging CNS metastasis

    - Off steroids that are used to minimize surrounding brain edema

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to MK-2206

    - Patients receiving any medications or substances that are inhibitors or inducers of
    cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible

    - Patients with diabetes or in risk for hyperglycemia should not be excluded from
    trials with MK-2206, but the hyperglycemia should be well controlled on oral agents
    before the patient enters the trial

    - Cardiovascular baseline corrected QT by Fridericia's (QTcF) > 450 msec (male) or QTcF
    > 470 msec (female) will exclude patients from entry on study

    - 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 MK-2206

    - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
    therapy are ineligible

    - No other prior malignancy is allowed except for the following: adequately treated
    basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
    stage I or II cancer from which the patient is currently in complete remission, or
    any other cancer from which the patient has been disease free for five years

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall response rate (CR+PR) evaluated using Response Evaluation Criteria in Solid Tumors version 1.1

    Secondary Outcome Measures

    DR

    OS

    PFS

    Validation of the enrichment biomarker signature in metastatic sites

    Trial Keywords