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A Phase 2 Study of MK-2206 in Previously Treated Metastatic Colorectal Cancer Patients Enriched for PTEN Loss and PIK3CA Mutation

Phase 2
18 Years
Open (Enrolling)
Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Colon, Signet Ring Adenocarcinoma of the Rectum, 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

Thank you

Trial Information

A Phase 2 Study of MK-2206 in Previously Treated Metastatic Colorectal Cancer Patients Enriched for PTEN Loss and PIK3CA Mutation


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


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

V. To determine effect of PTEN, v-raf murine sarcoma viral oncogene homolog B1 (BRAF),
PIK3CA, and v-akt murine thymoma viral oncogene homolog 1 (AKT) mutations and
semi-quantitative grading of PTEN expression on clinical response.


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

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

Inclusion Criteria:

- Patients must have histologically confirmed, radiologically measurable metastatic or
unresectable colorectal adenocarcinoma that is amenable to image-guided biopsy and
for which standard curative or palliative measures do not exist or are no longer
effective; disease in previously radiated regions may not be considered measurable
unless there has been demonstrated progression in the lesion

- Patients must have failed available therapy for the treatment of advanced colorectal
cancer; this is defined as progressive disease during or within 6 months after
fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab, and for v-Ki-ras2 Kirsten rat
sarcoma viral oncogene homolog (KRAS) wild-type patients, anti-epidermal growth
factor receptor (EGFR) antibody (cetuximab or panitumumab) containing therapies, with
most recent progression by Response Evaluation Criteria in Solid Tumors (RECIST)
criteria; patients who had at least stable disease as best response on their prior
therapies (listed above) should have received at least 2 months (approximately 60
days) of treatment; for oxaliplatin-based therapy, failure of therapy will also
include patients who progressed within 12 months of adjuvant therapy and patients who
had oxaliplatin stopped due to toxicity

- 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 within normal institutional limits

- 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 within normal institutional limits 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 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate (CR+PR) evaluated using RECIST version 1.1

Outcome Time Frame:

Up to 18 months

Safety Issue:


Principal Investigator

Edmund Kopetz

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

Related Keywords:

  • Mucinous Adenocarcinoma of the Colon
  • Mucinous Adenocarcinoma of the Rectum
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Signet Ring Adenocarcinoma of the Colon
  • Signet Ring Adenocarcinoma of the Rectum
  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Cystadenocarcinoma



M D Anderson Cancer CenterHouston, Texas  77030