Endocrine Therapy + OSI-906 With or Without Erlotinib for Hormone-Sensitive Metastatic Breast Cancer

NCT01205685 | Terminated Phase 2 Results DMC

• 1 other identifier: VICC BRE 09112
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

Erlotinib attacks a part of cancer cells that helps them live and grow. Studies done in human beings show that this drug can make a difference in the way anti-estrogens work in hormone-sensitive breast cancers. OSI-906 attacks a different part of the cancer cell that helps them live and grow. Studies done in the laboratory show that OSI-906 can make a difference in the way anti-estrogens work in hormone-sensitive breast cancers.

Conditions

Hormone-sensitive Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Anti-tumor Activity of OSI-906

  Time to progression measured in months from study entry to date of disease progression

  From study entry to 6 months

Secondary Outcomes (3)

• Safety Profile Based on Number of Patients With Each Worst-grade Toxicity

  Every 4 weeks up to 24 weeks

• Number of Participants With Tumor Response Per RECIST

  Every 12 weeks to tumor progression

• Correlative Studies

  < or = to 2 weeks before initiation of Phase II study treatment period

Study Arms (1)

OSI-906 + Erlotinib + Letrozole + Goserelin

EXPERIMENTAL

* OSI-906 in a pill form, by mouth, twice a day (12 hours a part) * Erlotinib in a pill form, by mouth, once a day * Letrozole in a pill form, by mouth, once a day * Goserelin, by injection once per month for women who are pre-menopausal

Drug: OSI-906; Drug: Erlotinib; Drug: Letrozole; Drug: Goserelin

Interventions

OSI-906 DRUG

In a pill form by mouth, twice a day (12 hours apart) During the safety run portion of the study" * Dose level 2 = 150 mg twice a day * Dose level 1 = 100 mg twice a day * Dose level -1 = 100 mg twice a day * Dose level -2 = 100 mg twice a day

OSI-906 + Erlotinib + Letrozole + Goserelin

Erlotinib DRUG

During the safety run phase of the study: * Dose Level 2 = 100 mg/d * Dose Level 1 = 100 mg/d * Dose Level -1= 75 mg/d * Dose Level -2 = 50 mg/d

OSI-906 + Erlotinib + Letrozole + Goserelin

Letrozole DRUG

In a pill form, by mouth, once per day at 2.5 mg/d.

OSI-906 + Erlotinib + Letrozole + Goserelin

Goserelin DRUG

For pre-menopausal patients only. Given as an injection once a month at 3.6 mg/month.

OSI-906 + Erlotinib + Letrozole + Goserelin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must provide informed written consent.
• Patients must be ≥18 years of age.
• ECOG performance status 0-1.
• Patients with clinical stage IV invasive mammary carcinoma, previously documented by histological analysis, which is ER-positive and/or PR-positive by immunohistochemistry (IHC), which had previous endocrine therapy in the metastatic setting or had metastatic recurrence within 6 months of adjuvant endocrine therapy. Patients may have either measurable or non-measurable disease, both are allowed.
• Patients whose breast cancers are also HER2-overexpressed (IHC 3+ or FISHpositive) need to have had previous treatment exposure to trastuzumab (Herceptin®)
• Life expectancy ≥ 6 months
• Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained less than 2 weeks from study entry. This includes:
• ANC ≥1250/mm3
• Platelet count ≥100,000/mm3
• Creatinine ≤1.5X upper limits of normal
• Bilirubin, SGOT, SGPT ≤ 1.5 X upper limits of normal if no liver metastasis present\*
• Bilirubin, SGOT, SGPT, alkaline phosphatase ≤ 3 X upper limits of normal if liver metastasis present\* \*for patients with Gilbert's syndrome, direct bilirubin will be measured instead of total bilirubin
• Able to swallow and retain oral medication.
• Pre-menopausal patients must have a negative pregnancy test prior to participating in the study. Women of childbearing age and their male counter parts should use a barrier method of contraception during and for 3 months following protocol therapy.
• Post-menopausal female subjects should be defined prior to protocol enrollment by any of the following:

You may not qualify if:

• Locally recurrent resectable breast cancer.
• Pregnant or lactating women.
• Patients must not have had \> than 4 prior chemotherapy treatments in the metastatic setting. This restriction does not include endocrine therapies or single agent biologic therapies.
• Use of CYP3A4 and CYP1A2 modifiers or drugs that prolong QTcF with high risk for Torsade de Pointes (see Appendix A)
• Any kind of malabsorption syndrome significantly affecting gastrointestinal function.
• History of other malignancy within 5 years prior to enrollment. Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible.
• Patients with baseline QTcF\> 450 msec
• Patients with diabetes, glucose \> 160 mg/dL or receiving ongoing antihyperglycemic therapies
• Uncontrolled intercurrent illness including, but not limited to:
• ongoing or active infection requiring parenteral antibiotics
• impairment of lung function (COPD \> grade 2, lung conditions requiring oxygen therapy)
• symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)
• unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
• uncontrolled hypertension (systolic blood pressure \>180 mm Hg or diastolic blood pressure \>100 mm Hg, found on two consecutive measurements separated by a 1-week period despite adequate medical support)
• clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment \[National Cancer Institute -Common Terminology Criteria for Adverse Events, Version 4.0, grade 3\]

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead

Study Sites (3)

Vanderbilt-Ingram Oncology Cool Springs

Franklin, Tennessee, 37067, United States

Location

Vanderbilt One Hundre Oaks

Nashville, Tennessee, 37204, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Erlotinib Hydrochloride; Letrozole; Goserelin

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. Ingrid Mayer
• Organization: Vanderbilt-Ingram Cancer Center

ingrid.mayer@vanderbilt.edu

615-936-2033

Study Officials

• Ingrid Mayer, M.D.

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist

Study Record Dates

• First Submitted: September 17, 2010
• First Posted: September 20, 2010
• Study Start: May 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: September 11, 2012
• Results First Posted: September 11, 2012

Record last verified: 2012-08

Locations

US (3)