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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01205685
Recruitment Status : Terminated (PI closed study early, all patients experienced severe toxicities and progressed)
First Posted : September 20, 2010
Results First Posted : September 11, 2012
Last Update Posted : September 11, 2012
Information provided by (Responsible Party):
Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center

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.

Condition or disease Intervention/treatment Phase
Hormone-sensitive Metastatic Breast Cancer Drug: OSI-906 Drug: Erlotinib Drug: Letrozole Drug: Goserelin Phase 2

Detailed Description:
The safety run component of this trial is to determine the safety profile of the OSI-906, erlotinib and anti-endocrine treatment combination. The phase II component evaluates the antitumor activity of the combination OSI-906, erlotinib and endocrine therapy.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Endocrine Therapy in Combination With OSI-906 (an IGF-1R Inhibitor) and Erlotinib (Tarceva®, an EGFR Inhibitor) in Patients With Hormone-sensitive Metastatic Breast Cancer
Study Start Date : May 2010
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: OSI-906 + Erlotinib + Letrozole + Goserelin
  • 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

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

Drug: Erlotinib

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

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

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

Primary Outcome Measures :
  1. Anti-tumor Activity of OSI-906 [ Time Frame: From study entry to 6 months ]
    Time to progression measured in months from study entry to date of disease progression

Secondary Outcome Measures :
  1. Safety Profile Based on Number of Patients With Each Worst-grade Toxicity [ Time Frame: Every 4 weeks up to 24 weeks ]
    According to National Cancer Institute Common Toxicity Criteria for Adverse Events with 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening/disabling, and 5 = death.

  2. Number of Participants With Tumor Response Per RECIST [ Time Frame: Every 12 weeks to tumor progression ]
    Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

  3. Correlative Studies [ Time Frame: < or = to 2 weeks before initiation of Phase II study treatment period ]
    Biomarkers associated with response to OSI-906 + Erlotinib + Letrozole + Goserelin

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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:

    • Subjects at least 55 years of age;
    • Subjects under 55 years of age and amenorrheic for at least 12 months or follicle-stimulating hormone (FSH) values ≥40 IU/L and estradiol levels

      ≤20 IU/L;

    • Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months.
  • Patients 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. Patients who have received prior radiotherapy must have recovered from any toxicity induced by this treatment (toxicity grade ≤ 1).
  • Patients must be disease-free of prior invasive cancers for > 5 years with the exception of basal or squamous cancer of the skin or cervical carcinoma in situ.
  • Subjects must complete all screening assessments as outlined in the protocol.
  • Patients must have available tissue (archived formalin-fixed paraffin embedded blocks (FFPB) or fresh frozen tissue from original diagnosis or metastatic setting)for correlative studies. Tissue needs to be sent to VUMC (see Appendix E) at the time of registration. Patients will not be able to start study drugs without tissue availability.

Exclusion Criteria:

  • 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]
    • psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
  • Patients with symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than 3 weeks from completion of radiation treatment and not taking steroids or therapeutic anticonvulsants that are CYP3A4 modifiers)
  • Patients with asymptomatic brain metastasis on prophylactic anticonvulsants that are CYP3A4 modifiers
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol. Patients must have discontinued the above cancer therapies for 1 week prior to the first dose of study medication, as well as recovered from toxicity (to ≤ than grade 1, except for alopecia, neuropathy, and ANC, which should be ≥ 1250/mm3) induced by previous treatments. Any other investigational drugs should be discontinued 2 weeks prior to the first dose of study medication.
  • Prior therapy with an IGF-1R inhibitor

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01205685

United States, Tennessee
Vanderbilt-Ingram Oncology Cool Springs
Franklin, Tennessee, United States, 37067
Vanderbilt One Hundre Oaks
Nashville, Tennessee, United States, 37204
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Principal Investigator: Ingrid Mayer, M.D. Vanderbilt-Ingram Cancer Center

Responsible Party: Ingrid Mayer, MD, Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center Identifier: NCT01205685     History of Changes
Other Study ID Numbers: VICC BRE 09112
First Posted: September 20, 2010    Key Record Dates
Results First Posted: September 11, 2012
Last Update Posted: September 11, 2012
Last Verified: August 2012

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immune System Diseases
Erlotinib Hydrochloride
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal