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:

Completed

Phase:

Phase 2

Trial Eligibility

Document

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

  • ORG STUDY ID: NCI-2013-00487
  • SECONDARY ID: NCI-2013-00487
  • SECONDARY ID: 2012-0431
  • SECONDARY ID: 9340
  • SECONDARY ID: N01CM00039
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01802320

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

Interventions

DrugSynonymsArms
Akt Inhibitor MK2206MK2206Treatment (Akt inhibitor MK2206)

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

NameTypeDescriptionInterventions
Treatment (Akt inhibitor MK2206)ExperimentalAkt 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.
  • 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (CR+PR) Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Up to 18 months
Safety Issue:
Description:Complete Response (CR): Disappearance all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. Partial Response (PR): > 30% decrease in sum diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): > 20% increase in sum diameters of target lesions, reference smallest sum on study (includes baseline sum if smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase of >5 mm. (Note: appearance of 1/> new lesions also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters while on study.

Secondary Outcome Measures

Measure:Duration of Tumor Response (DR)
Time Frame:From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 18 months
Safety Issue:
Description:Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for DR.
Measure:Overall Survival (OS)
Time Frame:Up to 18 months
Safety Issue:
Description:Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for OS.
Measure:Progression-free Survival (PFS)
Time Frame:From start of treatment to time of progression or death, whichever occurs first, assessed up to 18 months
Safety Issue:
Description:Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for PFS.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

September 20, 2019