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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01205685
• Date of registration: 17/09/2010
• Primary sponsor: Vanderbilt-Ingram Cancer Center
• Public title: Endocrine Therapy + OSI-906 With or Without Erlotinib for Hormone-Sensitive Metastatic Breast Cancer
• Scientific 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
• Date of first enrolment: May 2010
• Target sample size: 11
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01205685
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Ingrid Mayer, M.D.
• Affiliation: Vanderbilt-Ingram Cancer Center

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Hormone-sensitive Metastatic Breast Cancer

Intervention(s)

Drug: Erlotinib

Drug: Goserelin

Drug: Letrozole

Drug: OSI-906

Primary Outcome(s)

Anti-tumor Activity of OSI-906 [Time Frame: From study entry to 6 months]

Secondary Outcome(s)

Correlative Studies [Time Frame: < or = to 2 weeks before initiation of Phase II study treatment period]

Number of Participants With Tumor Response Per RECIST [Time Frame: Every 12 weeks to tumor progression]

Safety Profile Based on Number of Patients With Each Worst-grade Toxicity [Time Frame: Every 4 weeks up to 24 weeks]

Secondary ID(s)

VICC BRE 09112

Source(s) of Monetary Support

Please refer to primary and secondary sponsors