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Estrogen Receptor PositivePhase 1NCT01344031

MK2206 in Combination With Anastrozole, Fulvestrant, or Anastrozole and Fulvestrant in Treating Postmenopausal Women With Metastatic Breast Cancer

A Phase 1 study testing Akt Inhibitor MK2206, Anastrozole and Fulvestrant in people with Estrogen Receptor Positive and Invasive Breast Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and the best dose of MK 2206 (Akt inhibitor MK2206) when given with anastrozole, fulvestrant, or anastrozole and fulvestrant in treating postmenopausal women with breast cancer that has spread to other parts of the body. Estrogen can cause the growth of breast cancer cells. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Akt Inhibitor MK2206, Anastrozole and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
21 Apr 2011to 1 Jul 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed invasive breast cancer that is metastatic stage IV or recurrent metastatic (histologic/cytologic confirmation of recurrence preferred, but not required)
  • Either the primary or the metastatic tumor must be positive for estrogen-receptor (> 1% tumor cell staining by immunohistochemistry or an Allred score of >= 3 by immunohistochemistry)
  • Patient must have measurable or non-measurable lesions (defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria)
  • Note: to be eligible for the FDG PET imaging studies in Phase IA, the presence of measurable lesions of at least 1.5 cm or the presence of bone lesions is required
  • Patients may have undergone any number of prior lines of chemotherapy or endocrine regimens but must not have a history of disease progression on anastrozole (Phase IA and Phase IB), fulvestrant (Arm C), or both anastrozole and fulvestrant (Arm D)
  • Phase IA and IB:
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  • Currently being treated with anastrozole with no evidence of disease progression OR
  • Currently being treated with letrozole or exemestane with no evidence of disease progression and willing to switch to anastrozole for study enrollment OR
  • Considering switching to anastrozole due to disease progression from the most recent anti-cancer therapy
  • Arm C:
  • Currently being treated with fulvestrant with no evidence of disease progression OR
  • Considering switching to fulvestrant due to disease progression from the most recent anti-cancer therapy
  • Arm D:
  • Currently being treated with either anastrozole or fulvestrant with no evidence of disease progression OR
  • Currently being treated with letrozole or exemestane with no evidence of disease progression and willing to switch to anastrozole for study enrollment
  • Considering switching to anastrozole or fulvestrant due to disease progression from the most recent anti-cancer therapy
  • Patients must be postmenopausal women as defined by one of the following:
  • Women > 60 years
  • Women =< 60 years with spontaneous cessation of menses > 12 months prior to registration
  • Women =< 60 years with cessation of menses of duration < 12 months or secondary to hysterectomy AND an follicle stimulating hormone (FSH) level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration
  • Women =< 60 years on hormonal replacement therapy who have discontinued hormonal therapy AND an FSH level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration
  • Status post bilateral surgical oophorectomy
  • Premenopausal women on a gonadotropin-releasing hormone (GnRH) analog
  • Patients must have a life expectancy greater than 4 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Total bilirubin not above the institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine not above the institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • If patients have diabetes mellitus, fasting glucose must be =< 120 mg/dL and hemoglobin (Hb)A1c =< 8%
  • Women of childbearing potential must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, the patient should inform the treating physician immediately
  • Patients with known brain metastases are eligible if stable (no evidence of local progression) >= 3 months after local therapy and are off steroid
  • Patients who are eligible for this study may also be eligible for and participate in National Cancer Institute (NCI) Protocol 9167, titled "Positron Emission Tomography (PET) with 18F-Fluoroestradiol (FES) as a Predictor of Response in Patients with Breast Cancer Scheduled to Be Treated with MK-2206 in Combination with Either an Aromatase Inhibitor or Fulvestrant on NCI Protocol 8762," in which case the FES-PET in Protocol 9167 has to be performed a minimum of 48 hours and a maximum of 30 days before the first dose of MK-2206; in addition, all FES-related side effects must have resolved before the first dose of MK-2206
  • Patients must have the ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients may not have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; patient must have recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study
  • Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 450 3A4) are ineligible
  • Note: one week washout period is required in patients who were previously taking strong inhibitors or inducers of CYP450 3A4; patients who are currently taking moderate inhibitors or inducers of CYP450 3A4 are encouraged to switch to other medications that do not interact with CYP450 3A4
  • 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 (i.e. HbA1c =< 8% and fasting glucose =< 120 mg/dL)
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  • Cardiovascular: baseline QT Fridericia formula (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study
  • Patients may not have 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 or nursing patients are excluded from the study
  • Patients with known human immunodeficiency virus (HIV) positive status are excluded from this study
  • Patients may not have had disease progression on anastrozole (Phase IA and Phase IB), fulvestrant (Arm C), both anastrozole and fulvestrant (Arm D) in either the neoadjuvant, adjuvant (defined as disease recurrence identified within 6 months of adjuvant discontinuation), or metastatic setting
  • Patients may not have had grade 3 or intolerable grade 2 adverse events during run-in aromatase inhibitor (AI) or fulvestrant therapy prior to starting MK-2206
  • Patients may not have had prior therapy with an AKT inhibitor

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 1 Trial of MK-2206 in Combination With Anastrozole, Fulvestrant, or Anastrozole Plus Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive Metastatic Breast Cancer

This phase I trial studies the side effects and the best dose of MK 2206 (Akt inhibitor MK2206) when given with anastrozole, fulvestrant, or anastrozole and fulvestrant in treating postmenopausal women with breast cancer that has spread to other parts of the body. Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole or fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving Akt inhibitor MK2206 together with anastrozole, fulvestrant, or anastrozole and fulvestrant may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of MK-2206 in combination with anastrozole based on toxicities observed during cycle 1 therapy. (Phase IA) II. To evaluate the tolerability of prolonged administration (3 months) of MK-2206 in combination with anastrozole at the MTD defined in Phase IA. (Phase IB) III. To determine the recommended phase II treatment dosing (RPTD) of MK-2206 in combination with anastrozole based on toxicities observed with prolonged drug administration. (Phase IB) IV. To determine the tolerability of fulvestrant (Arm C), or fulvestrant plus anastrozole (Arm D), respectively, in combination with MK-2206 (at the RPTD defined in Phase 1B). (Arms C and D) V. To determine the recommended phase II treatment dose (RPTD) of fulvestrant (Arm C) or fulvestrant plus anastrozole (Arm D), respectively, in combination with MK-2206 based on toxicities observed with prolonged drug administration (3 months). (Arms C and D) VI. To evaluate the toxicity profile of MK-2206 in combination with fulvestrant (Arm C) or fulvestrant plus anastrozole (Arm D), respectively, with prolonged drug administration. (Arms C and D)

SECONDARY OBJECTIVES:

  1. To evaluate the toxicity profile of MK-2206 in combination with anastrozole, or fulvestrant, or anastrozole plus fulvestrant.

II. To evaluate the clinical benefit rate (CBR: complete response [CR]+partial response [PR]+stable disease [SD] > 6 months), response rate (CR+PR), and percent of patients progression free at 6 months with the treatment of MK-2206 in combination with anastrozole, or fulvestrant or anastrozole plus fulvestrant in patients with estrogen receptor positive (ER+) metastatic breast cancer.

III. To examine serum levels of estradiol prior to and following 1 cycle of MK-2206 therapy.

TERTIARY OBJECTIVES:

  1. To examine baseline tumor specimens for alterations in phosphatidylinositol 3 kinase (PI3K) and other pathway genes and to explore their relationship with treatment response.

II. To evaluate the effect of MK-2206 on tumor cell v-akt murine thymoma viral oncogene homolog 1 (AKT) signaling, proliferation, and apoptosis using serially collected tumor samples in available cases.

III. To examine changes in tumor cell glucose uptake by positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) at baseline and 24 h post day 1 MK-2206. (Phase IA) IV. To examine the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation status in circulating deoxyribonucleic acid (DNA) at baseline and following study therapy and to correlate with tumor tissue PIK3CA status and treatment response.

OUTLINE: This is a phase I, dose-escalation study of Akt inhibitor MK2206 followed by a recommended phase II dose (RPTD) study. Patients are assigned to the treatment arm that is currently open.

ARM A: Patients receive anastrozole orally (PO) on days 1-28. Beginning in course 2, patients receive Akt inhibitor MK-2206 PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: The RPTD of Akt inhibitor MK2206 with anastrozole is determined after 3 courses, administered as in Arm A.

ARM C: Patients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22, fulvestrant intramuscularly (IM) on day 1 and day 15 of course 1 and then on day 1 of each course in each subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM D: Patients receive Akt inhibitor MK2206 PO as in Arm A, anastrozole PO on days 1-28 and fulvestrant IM on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: As of 8/19/2015, in all Arms, patients no longer receive Akt inhibitor MK2206.

After completion of study therapy, patients are followed up for 30 days.

Being tested
Akt Inhibitor MK2206, Anastrozole, Fulvestrant, Laboratory Biomarker Analysis
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Akt Inhibitor MK2206Drug

    Also called MK2206

    Given PO

  • AnastrozoleDrug

    Also called Anastrazole, Arimidex, ICI D1033, ICI-D1033

    Given PO

  • FulvestrantDrug

    Also called Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780

    Given IM

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01344031
Study groupRoleWhat they receive
Arm A (anastrozole and Akt inhibitor MK2206)ExperimentalPatients receive anastrozole PO on days 1-28. Beginning in course 2, patients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: As of 8/19/2015, patients no longer receive Akt inhibitor MK2206.
Receives: Drug: Akt Inhibitor MK2206; Drug: Anastrozole; Other: Laboratory Biomarker Analysis
Arm B (Akt inhibitor MK2206 and anastrozole)ExperimentalThe RPTD of Akt inhibitor MK2206 with anastrozole is determined after 3 courses, administered as in Arm A. NOTE: As of 8/19/2015, patients no longer receive Akt inhibitor MK2206.
Receives: Drug: Akt Inhibitor MK2206; Drug: Anastrozole; Other: Laboratory Biomarker Analysis
Arm C (Akt inhibitor MK2206 and fulvestrant)ExperimentalPatients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22, fulvestrant IM on day 1and day 15 of course 1 and then on day 1 of each course in each subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: As of 8/19/2015, patients no longer receive Akt inhibitor MK2206.
Receives: Drug: Akt Inhibitor MK2206; Drug: Fulvestrant; Other: Laboratory Biomarker Analysis
Arm D (Akt inhibitor MK2206, anastrozole, fulvestrant)ExperimentalPatients receive Akt inhibitor MK2206 PO as in Arm A, anastrozole PO on days 1-28 and fulvestrant IM on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: As of 8/19/2015, patients no longer receive Akt inhibitor MK2206.
Receives: Drug: Akt Inhibitor MK2206; Drug: Anastrozole; Drug: Fulvestrant; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD of Akt inhibitor MK-2206 in combination with anastrozole determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) (Phase IA)

    Data analysis for the study will be descriptive in nature. Demographic and clinical characteristics of the subjects, toxicity by grade, adverse events, serious adverse events and death will be listed and summarized using descriptive statistics for each dose level.

    Measured: 4 weeks

  2. RPTD of Akt inhibitor MK-2206 in combination with anastrozole evaluated by the tolerability of prolonged administration at the MTD assessed by CTCAE v4.0 (Phase IB)

    Data analysis for the study will be descriptive in nature. Demographic and clinical characteristics of the subjects, toxicity by grade, adverse events, serious adverse events and death will be listed and summarized using descriptive statistics for each dose level.

    Measured: 3 months

  3. RPTD of fulvestrant in combination with Akt inhibitor MK-2206 assessed by CTCAE v4.0 (ARM C)

    Data analysis for the study will be descriptive in nature. Demographic and clinical characteristics of the subjects, toxicity by grade, adverse events, serious adverse events and death will be listed and summarized using descriptive statistics for each dose level.

    Measured: 3 months

  4. RPTD of anastrozole plus fulvestrant in combination with Akt inhibitor MK-2206 assessed by CTCAE v4.0 (ARM D)

    Data analysis for the study will be descriptive in nature. Demographic and clinical characteristics of the subjects, toxicity by grade, adverse events, serious adverse events and death will be listed and summarized using descriptive statistics for each dose level.

    Measured: 3 months

Secondary outcomes (3)

  1. Incidence of toxicity, assessed by CTCAE v4.0

    Measured: Up to 30 days post-treatment

  2. Clinical benefit rate (CR+PR+SD for more than 6 months)

    Measured: Up to 30 days post-treatment

  3. Serum levels of estradiol prior to and following 1 course of Akt inhibitor MK-2206 therapy

    Measured: Up to day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2011 (estimated)
  2. Study start21 Apr 2011
  3. Primary completion1 Jul 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01344031
Sponsor's protocol ID
NCI-2011-02586
Other IDs
NCI-2011-02586, 201010701, WU-201010701, CDR0000699394, 201010701, 8762, N01CM00099, P30CA091842
Status last verified
May 2018
First submitted
27 Apr 2011
Last updated
23 Jul 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Akt Inhibitor MK2206, Anastrozole and Fulvestrant in people with Estrogen Receptor Positive and Invasive Breast Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of Akt inhibitor MK-2206 in combination with anastrozole determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) (Phase IA) (time frame: 4 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01344031.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2018; AzTrials last refreshed its copy on 8 Nov 2026.

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