MDACC Study Summary 2010-0296

Study Summary
No. 2010-0296:.......Breast......Ricardo Alvarez......Breast Medical Oncology

Study Summary Title



Study Summary Number:	2010-0296

Study Title:	A Phase II Study of TKI258 (Dovitinib Lactate) as Salvage Therapy in Patients with Stage IV HER2-negative IBC and Local or Distant Relapse

Physician

New Patient Referral



Name:	Ricardo Alvarez	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Breast Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-563-3735 Contact us about clinical trials

General Information



Disease Group:	Breast	Supported By:	Novartis

Phase of Study:	Phase II	Return Visit:

Treatment Agents:	TKI258	Home Care:

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:


Description/ Intervention:	The goal of this clinical research study is to learn if dovitinib can help to control inflammatory breast cancer. The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary

To determine an overall response (complete response [CR], partial response [PR] or stable disease [SD]) of dovitinib in patients with HER2-normal, local or distant relapse of metastatic inflammatory breast cancer

Secondary

· To evaluate safety analysis measures in terms of type, frequency and severity of adverse event reactions reported according to CTCAE v4.0

Exploratory Biomarkers:
· To explore the predictive values of baseline FGFR-R1, and VEGF-R1, signaling in tumor tissue (primary tumor or metastasis) before and during treatment with dovitinib.

· To determine the effect of dovitinib on the presence of CTC and CTCs with epithelial and/or EMT gene expression in PB.

To collect and archive biopsy tumor tissue, serum and plasma for later hypothesis generating associations

Study Status Information



Study Activation / Registration Date:	01/27/2012

IRB Review and Approval Date:	01/27/2012

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients have histological confirmation of breast carcinoma with a clinical diagnosis of IBC based on presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d orange), with or without an underlying palpable mass involving the majority of the skin of the breast. Pathological evidence of dermal lymphatic invasion should be noted but is not required for diagnosis.

2) Patients have stage IV disease with local or distant relapse

3) Patients have negative HER2 expression by IHC (defined as 0 or1+), or FISH. If HER2 is 2+, negative HER2 expression must be confirmed by FISH.

4) Patients are able to swallow and retain oral medication.

5) Patients have ECOG performance status 0-2.

6) Patients have received two or more standard chemotherapies for metastatic disease and have relapsed.

7) Patients have ability and willingness to sign written informed consent.

8) Patients are 18 years of age or older.

9) Female patients of childbearing potential (A female not free from menses > 2 years or not surgically sterilized) must be willing to use highly effective contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study. Highly effective contraception, defined as male condom with spermicide, diaphragm with spermicide, intra-uterine device. Highly effective contraception must be used by both sexes during the study and must be continued for 8 weeks after the end of study treatment. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.

10) Female patients of childbearing potential must have negative serum pregnancy test </=14 days prior to starting study treatment.

11) If Patients have been treated with anti-VEGF agents, such as Bevacizumab, last dose must be > 4 weeks.

12) Patients have biopsy tissue of the metastatic disease (including chest wall or regional nodes) available (paraffin blocks or up to 20 unstained slides), if no biopsy tissue available, a biopsy (or thoracentesis if patient has pleural effusion only) of the metastatic disease will be performed to confirm the diagnoses.

13) Serum total bilirubin must be within Upper Limited Normal (T. Bilirubin ULN=1.0 mg/dl)

14) AST and ALT must be < 2.5 x ULN(with or without liver metastases).

Exclusion Criteria:

1) Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiation therapy and biological therapy) while taking study medication.

2) Cirrhosis of liver, or known hepatitis B or C infection have hepatic impairment Child-Pugh Score of B or worse.

3) ANC < 1.5

4) Patients have an active infection and require IV or oral antibiotics.

5) Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) History or presence of serious uncontrolled ventricular arrhythmias or presence of atrial fibrillation; b) Clinically significant resting bradycardia (< 50 beats per minute); c) LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (which ever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (which ever is higher). d) Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE); e) Uncontrolled hypertension defined by an SBP>150 and/or a DBP>100 mm Hg with or without anti-hypertensive medication.

6) History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.

7) Patients have a concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients safety.

8) Patients with only locally or regionally confined disease without evidence of metastatic disease.

Links

Registration Number: NCT01262027
Study Information on Clinical Trials Registry (clinicaltrials.gov)