Endocrine Therapy + OSI-906 With or Without Erlotinib for Hormone-Sensitive Metastatic Breast Cancer
This study has been terminated.
(PI closed study early, all patients experienced severe toxicities and progressed)
Information provided by (Responsible Party):
Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center
First received: September 17, 2010
Last updated: August 10, 2012
Last verified: August 2012
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.
Hormone-sensitive Metastatic Breast Cancer
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
Secondary Outcome Measures:
- Safety Profile Based on Number of Patients With Each Worst-grade Toxicity [ Time Frame: Every 4 weeks up to 24 weeks ] [ Designated as safety issue: Yes ]
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.
- Number of Participants With Tumor Response Per RECIST [ Time Frame: Every 12 weeks to tumor progression ] [ Designated as safety issue: No ]
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
- Correlative Studies [ Time Frame: < or = to 2 weeks before initiation of Phase II study treatment period ] [ Designated as safety issue: No ]
Biomarkers associated with response to OSI-906 + Erlotinib + Letrozole + Goserelin
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||July 2011 (Final data collection date for primary outcome measure)
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
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
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
In a pill form, by mouth, once per day at 2.5 mg/d.
For pre-menopausal patients only. Given as an injection once a month at 3.6 mg/month.
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.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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:
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01205685
|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 |
Vanderbilt-Ingram Cancer Center
||Ingrid Mayer, M.D.
||Vanderbilt-Ingram Cancer Center
No publications provided
||Ingrid Mayer, MD, Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center
History of Changes
|Other Study ID Numbers:
||VICC BRE 09112
|Study First Received:
||September 17, 2010
|Results First Received:
||June 7, 2012
||August 10, 2012
||United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 25, 2015
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors