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Metastatic Breast CancerPhase 1NCT01240928

MK-2206+Endocrine Therapy in Patients With Hormone Receptor-Positive Breast Cancer

A Phase 1 study testing MSK-2206, Exemestane and Goserelin in people with Metastatic Breast Cancer, run by Vanderbilt-Ingram Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a phase Ib trial that evaluates the safety and tolerability of MK-2206 given in combination with exemestane +/- goserelin in pre- and post-menopausal patients with hormone receptor-positive metastatic breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
MSK-2206, Exemestane and Goserelin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Start not givento not given
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

  • Clinical stage IV invasive mammary carcinoma, documented by histological analysis, ER-positive and/or PR-positive by immunohistochemistry (IHC), previous endocrine therapy in the metastatic setting or had metastatic recurrence within 6 months of adjuvant endocrine therapy. May have measurable or non-measurable disease, both are allowed. Any number of prior hormone or chemotherapy agents are acceptable
  • Female and ≥ 18 years of age on the day of signing informed consent
  • Performance status of 0 or 1 on the ECOG Performance Scale
  • Adequate organ function as indicated by the following laboratory values:
  • Hematological:
  • Absolute neutrophil count (ANC) ≥ 1,500 /μL
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  • Platelets ≥ 100,000 /μL
  • Hemoglobin ≥ 9 g/dL
  • Renal:
  • -Serum creatinine or calculated creatinine clearance† - ≤ 1.5 x upper limit of normal (ULN) OR ≥60 mL/min for patients with creatinine levels > 1.5 x institutional ULN
  • Hepatic:
  • Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤5 x ULN in patients with known liver metastasis
  • Coagulation:
  • Prothrombin time (PT)/INR ≤ 1.2 x ULN
  • Partial thromboplastin time (PTT) ≤ 1.2 x ULN
  • Metabolic:
  • -HBA1C ≤ 8%
  • † Creatinine clearance calculated per institutional standard
  • ‡ Fasting defined as at least 8 hours without oral intake
  • Female patient of childbearing potential must have negative serum or urine pregnancy test β-hCG within 72 hours prior to receiving the first dose of study medication
  • Post-menopausal female subjects defined prior to protocol enrollment by any of the following:
  • At least 55 years of age
  • Under 55 years of age and amenorrheic for at least 12 months or follicle-stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels < or equal to 20IU/L
  • Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
  • Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent
  • Able to swallow capsules and has no surgical or anatomical condition that will preclude swallowing and absorbing oral medications on an ongoing basis
  • May receive concurrent radiation therapy to painful bone metastases or areas of impending bone fracture as long as radiation therapy is initiated prior to study entry. Those who have received prior radiotherapy must have recovered from any toxicity induced by this treatment (toxicity grade ≤ 1)

Who cannot join

  • Chemotherapy, radiotherapy, or biological therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If residual toxicity from prior treatment,toxicity must be ≤ Grade 1
  • Must be at least 4 weeks post-major surgical procedure, and all surgical wounds must be fully healed
  • Currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1
  • Known active 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: (1) no evidence of new or enlarging CNS metastasis (2)off steroids used to minimize surrounding brain edema
  • Primary central nervous system tumor
  • Known hypersensitivity to the components of study drug or its analogs
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  • History or current evidence of clinically significant heart disease including:
  • congestive heart failure, unstable angina pectoris,
  • cardiac arrhythmia,
  • history or current evidence of a myocardial infarction during the last 6 months,and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator,
  • baseline QTc prolongation > 450 msec (Bazett's Formula). Medications included in Arizona CERT Lists 1 and 2 (Appendix D) must be excluded. The concomitant use of drugs that are associated with increased risk for QT prolongation should be avoided in patients with congenital long QT syndrome (Appendix D, Arizona CERT List 3). Similarly, the concomitant use of drugs that are weakly associated with QT prolongation should be generally avoided (Appendix D, Arizona CERT List 4). Arizona CERT List 3 and 4 drugs should be used at the discretion of the Investigator and restricted where applicable. Any therapy given with these drugs should be used with caution, and patients receiving these medications should be carefully monitored.
  • Evidence of clinically significant bradycardia (HR <50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2), or patients taking beta blockers, non-dihydropyridine calcium channel blockers, or digoxin
  • Uncontrolled hypertension (i.e., 160/90 mHg SiBP). Patients who are controlled on antihypertensive medication will be allowed to enter the study
  • At significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent diarrhea)
  • Poorly controlled diabetes defined as HbA1C > 8%
  • History or current evidence of any condition, therapy, or lab abnormality that might confound the study results, interfere with the patient's participation for the full study duration, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with trial requirements
  • Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
  • Human Immunodeficiency Virus (HIV)-positive
  • Known history of Hepatitis B or C or active Hepatitis A
  • Symptomatic ascites or pleural effusion. Patient who is clinically stable following treatment for these conditions is eligible
  • Receiving treatment with oral corticosteroids (note: inhaled corticosteroids are permitted)

About this study

Official title: A Phase Ib Trial of MK-2206 (an AKT Inhibitor) in Combination With Endocrine Therapy in Patients With Hormone Receptor-Positive Breast Cancer

This is a phase Ib trial that evaluates the safety and tolerability of MK-2206 given in combination with exemestane +/- goserelin in pre- and post-menopausal patients with hormone receptor-positive metastatic breast cancer.

Read the detailed description

The phase II portion of this trial will be listed under a separate NCT number.

Being tested
MSK-2206, Exemestane, Goserelin
Medical subject headings
Breast Neoplasms

What participants receive

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

  • MSK-2206Drug

    Level 1: MK-2206 135mg weekly

  • ExemestaneDrug

    Level 1: Exemestane - 25mg daily

  • GoserelinDrug

    Level 1: Goserelin- 3.6mg monthly for pre-menopausal subjects only

Study groups in NCT01240928
Study groupRoleWhat they receive
MK-2206 + exemestane +/- goserelinExperimentalOral MK-2206 and oral exemestane and subcutaneous goserelin (for pre-menopausal participants only)
Receives: Drug: MSK-2206; Drug: Exemestane; Drug: Goserelin

What is being measured

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

  1. Tolerability of MK-2206 given in combination with exemestane +/- goserelin, as measured by maximum tolerated dose (MTD).

    The MTD will be defined as the highest dose tested in which a dose-limiting toxicity is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels.

    Measured: at 4 weeks

Secondary outcomes (2)

  1. Number of participants with adverse events as a measure of safety of MK-2206 when combined with exemestane +/- goserelin

    Number of participants with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death

    Measured: At 4 weeks

  2. Characterize the effect of MK-2206 in combination with exemestane +/- goserelin based on PI3K, AKT, and PTEN mutations, as measured by immunohistochemistry and the SNaPshot assay.

    Using tumor blocks from previous surgeries or fresh biopsies of accessible metastatic sites

    Measured: After collection of tumor tissue

Timeline

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

  1. First posted15 Nov 2010 (estimated)

Why it stopped: Funding not available, study did not open to accrual and will not open in future

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01240928
Sponsor's protocol ID
VICC BRE 1029
Status last verified
Aug 2013
First submitted
26 Oct 2010
Last updated
20 Aug 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MSK-2206, Exemestane and Goserelin in people with Metastatic Breast Cancer, run by Vanderbilt-Ingram Cancer Center.

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 28 inclusion and 23 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: withdrawn, as of the sponsor's last update on 20 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

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 was withdrawn before enrolling participants, so there are no results.

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?

Tolerability of MK-2206 given in combination with exemestane +/- goserelin, as measured by maximum tolerated dose (MTD). (time frame: at 4 weeks). 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 NCT01240928.

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 20 Aug 2013.

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