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Estrogen Receptor PositivePhase 1NCT01149356

RO4929097 And Exemestane in Treating Pre- and Postmenopausal Patients With Advanced or Metastatic Breast Cancer

A Phase 1 study testing Exemestane, Gamma-Secretase Inhibitor RO4929097 and Goserelin Acetate in people with Estrogen Receptor Positive and HER2/Neu Negative, run by National Cancer Institute (NCI) at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This partially randomized phase I trial is studying the side effects and the best dose of RO4929097 when given together with exemestane and to see how well it works compared to exemestane alone in treating premenopausal and postmenopausal patients with advanced or metastatic breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Exemestane, Gamma-Secretase Inhibitor RO4929097 and Goserelin Acetate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
4 sitesUnited States
Study dates
Oct 2010to Apr 2013
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of breast cancer
  • Locally advanced or metastatic disease for which curative measures are not effective
  • Relapsed disease with (or within 6 months of discontinuation of) an adjuvant nonsteroidal aromatase inhibitor or tamoxifen
  • Progressive disease during treatment with first- or second-line hormonal therapy that could include a nonsteroidal aromatase inhibitor, tamoxifen, or fulvestrant
  • Recurrent disease
  • No locally recurrent resectable disease
Show all 55Show fewer
  • Histologically confirmed estrogen receptor-positive (ER+) by IHC
  • Must have ≥ 5% strong staining for ER+ or ≥ 10% weak staining
  • Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques OR as ≥ 10 mm by spiral CT scan
  • No HER2/neu-positive disease
  • No known brain metastases
  • Pre- or postmenopausal status
  • ECOG performance status 0-1
  • Life expectancy ≥ 6 months
  • WBC ≥ 3,500/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 2 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Able to swallow and retain oral medication
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for ≥ 12 months after completion of study therapy
  • More than 5 years since other invasive cancer except basal or squamous cell cancer of the skin or cervical carcinoma in situ
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 or other agents used in the study
  • No history of torsades de pointes
  • No malabsorption syndrome or other condition that would interfere with intestinal absorption (e.g., ulcerative colitis)
  • Not serologically positive for hepatitis B or C, have a history of liver disease, other forms of hepatitis, or cirrhosis
  • No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection requiring parenteral antibiotics
  • Impairment of lung function (e.g., chronic obstructive pulmonary disease or lung conditions requiring oxygen therapy)
  • Symptomatic congestive heart failure (NYHA class III-IV heart disease)
  • Unstable angina pectoris, angioplasty, stenting, and or myocardial infarction within the past 6 months
  • Uncontrolled hypertension (systolic BP > 180 mm Hg or diastolic BP > 100 mm Hg on 2 consecutive measurements separated by a 1-week period) despite adequate medical support
  • Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, torsades de pointes, ventricular tachycardia that is symptomatic, or requiring treatment)
  • A requirement for antiarrthymics or other medications known to prolong QTC
  • Uncontrolled diabetes (hyperosmolar state, ketoacidosis, etc.)
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • No baseline QTcF > 450 msec (male) or > 470 msec (female)
  • See Disease Characteristics
  • Fully recovered from all previous adverse events
  • No prior exemestane for metastatic or recurrent breast cancer, or within the past 6 months in the adjuvant setting
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 2 weeks since prior radiotherapy
  • At least 2 weeks since prior and no other concurrent investigational agents
  • No prior exposure to γ-secretase inhibitors
  • No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
  • No other concurrent CYP3A4 substrates, inducers, or inhibitors
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies, including chemotherapy, radiotherapy, surgery, immunotherapy, hormonal therapy, or biologic therapy
  • No concurrent medications or food that may interfere with the metabolism of gamma-secretase inhibitor RO4929097, including ketoconazole and grapefruit juice
  • No concurrent antiarrhythmics or other medications known to prolong QTc

Who cannot join

None listed.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase I Dose Escalation Trial of RO4929097 Administered in Combination With Exemestane in Pre- and Postmenopausal Patients With ER + Metastatic Breast Cancer

This partially randomized phase I trial is studying the side effects and the best dose of RO4929097 when given together with exemestane and to see how well it works compared to exemestane alone in treating premenopausal and postmenopausal patients with advanced or metastatic breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving exemestane together with RO4929097 may kill more breast cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum-tolerated dose of gamma-secretase inhibitor RO4929097 (RO4929097) in combination with exemestane in pre- and postmenopausal patients with estrogen receptor-positive (ER+) advanced or metastatic breast cancer.

II. Determine the safety and tolerability of this regimen in these patients. III. Determine the progression-free survival of patients treated with exemestane with vs without RO4929097.

SECONDARY OBJECTIVES:

  1. Determine the overall tumor response rate in patients treated with these regimens.

II. Determine the overall survival of patients treated with these regimens. III. Determine the safety of these regimens in these patients. IV. Determine the quality of life of patients treated with these regimens. V. Identify biomarkers of response to treatment or toxicity.

OUTLINE: This is a multicenter, phase I, dose-escalation study of gamma-secretase inhibitor RO4929097.

Patients receive oral exemestane once daily on days 1-21 and oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are stratified according to menopausal status (pre- vs postmenopausal) and visceral disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive exemestane as in phase I and oral gamma-secretase inhibitor RO4929097 at the MTD determined in phase I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive exemestane as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

In addition to exemestane, pre-menopausal patients receive goserelin subcutaneously every 28 days. Patients may undergo blood and tissue sample collection for correlative studies.

Patients may complete quality-of-life questionnaires at baseline and periodically during study using the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B).

After completion of study therapy, patients are followed up for 4 weeks and then every 6 months thereafter.

Being tested
Exemestane, Gamma-Secretase Inhibitor RO4929097, Goserelin Acetate
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms

What participants receive

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

  • ExemestaneDrug

    Also called Aromasin, FCE-24304

    Given orally

  • Gamma-Secretase Inhibitor RO4929097Drug

    Also called RO4929097

    Given orally

  • Goserelin AcetateDrug

    Also called ZDX, Zoladex

    Given subcutaneously to premenopausal patients

Study groups in NCT01149356
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral exemestane once daily on days 1-21 and oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Exemestane; Drug: Gamma-Secretase Inhibitor RO4929097; Drug: Goserelin Acetate
Arm IIActive comparatorPatients receive exemestane as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Exemestane; Drug: Goserelin Acetate

What is being measured

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

  1. Incidence of treatment emergent adverse events (TEAEs) based on CTCAE version 3 grade

    Will be summarized by body system, preferred term, verbatim of adverse event, intensity, and relationship to each study drug (BMS-936558 and/or the peptide vaccine).

    Measured: Up to 70 days

  2. Time to relapse

    Time to relapse will be summarized using descriptive statistics.

    Measured: Up to 2 years

Secondary outcomes (1)

  1. Overall survival

    Measured: Up to 2 years

Timeline

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

  1. First posted23 Jun 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionDec 2012
  4. Study completionApr 2013

Why it stopped: Manufacturer discontinued drug development.

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01149356
Sponsor's protocol ID
NCI-2010-02181
Other IDs
NCI-2010-02181, MCC-8539, CDR0000675612, 8539, 8539, N01CM00100, P30CA076292
Status last verified
May 2015
First submitted
22 Jun 2010
Last updated
25 May 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Exemestane, Gamma-Secretase Inhibitor RO4929097 and Goserelin Acetate in people with Estrogen Receptor Positive and HER2/Neu Negative, run by National Cancer Institute (NCI) at 4 sites 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 55 inclusion and 0 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: stopped early, as of the sponsor's last update on 25 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 was stopped early (reason given: Manufacturer discontinued drug development.). Results are not available in the source record.

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?

Incidence of treatment emergent adverse events (TEAEs) based on CTCAE version 3 grade (time frame: Up to 70 days). The study lists 2 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 NCT01149356.

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 25 May 2015.

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