TKI258 for Metastatic Inflammatory Breast Cancer Patients

NCT01262027 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2010-0296NCI-2011-00299
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Metastatic inflammatory breast cancer; Stage IV disease; HER2-negative; Dovitinib; TKI258

Outcome Measures

Primary Outcomes (1)

• Overall Response (Complete Response [CR], Partial Response [PR] or Stable Disease [SD]) of Participants

  Number of participants experiencing CR, PR or SD as defined by Response Evaluation Criteria In Solid Tumors (RECIST). Response is anyone who experiences SD, CR or PR in first 6 months. CR: Disappearance clinical evidence active tumor by evaluation, mammogram \& ultrasound. No symptoms or evidence of residual invasive tumor, including no residual tumor in axillary lymph nodes. PR: 50%/\> decrease for minimum 4 weeks in measurable lesion determined by product of perpendicular diameters of lesion. Every lesion should not regress to qualify as PR; however, if lesion progresses or if new lesions appear, response cannot be classified as PR. Minor Response \[MR\]: Decreases in tumor masses insufficient to qualify as partial remission, i.e. \<50%. SD: Between MR \& PD. PD: Increase 25% measured lesion from baseline. New lesions constitutes increasing disease. Mixed responses consid

  6 months

Secondary Outcomes (1)

• Safety Analysis of Dovitinib: Most Frequently Reported Treatment-related Adverse Event (AEs)

  6 months

Study Arms (1)

Dovitinib

EXPERIMENTAL

A complete treatment cycle defined as 28 days or 4 weeks (+/- 2 days). Patients receive a single daily oral dose of 500 mg of dovitinib for 5 consecutive days, followed by a 2-day rest period (5 days on/2 days off schedule).

Drug: Dovitinib

Interventions

Dovitinib DRUG

500 mg by mouth for 5 consecutive days, followed by a 2-day rest period (5 days on/2 days off schedule) for every 28 day cycle.

Also known as: TKI258

Dovitinib

Eligibility Criteria

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

You may qualify if:

• 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.
• Patients have stage IV disease with local or distant relapse
• Patients have negative HER2 expression by IHC (defined as 0 or1+), or fluorescence in situ hybridization (FISH). If HER2 is 2+, negative HER2 expression must be confirmed by FISH.
• Patients are able to swallow and retain oral medication.
• Patients have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients have received two or more standard chemotherapies for metastatic disease and have relapsed.
• Patients have ability and willingness to sign written informed consent.
• Patients are 18 years of age or older.
• 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.
• Female patients of childbearing potential must have negative serum pregnancy test \</=14 days prior to starting study treatment.
• If Patients have been treated with anti-vascular endothelial growth factor (VEGF) agents, such as Bevacizumab, last dose must be \> 4 weeks.
• 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.
• Serum total bilirubin must be within Upper Limited Normal (T. Bilirubin upper limit of normal (ULN)=1.0 mg/dl)
• AST and ALT must be \< 2.5 x ULN(with or without liver metastases).

You may not qualify if:

• Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiation therapy and biological therapy) while taking study medication.
• Cirrhosis of liver, or known hepatitis B or C infection have hepatic impairment Child-Pugh Score of B or worse.
• Absolute neutrophil count (ANC) \< 1.5
• Patients have an active infection and require IV or oral antibiotics.
• 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) left ventricular ejection fraction (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 diastolic blood pressure (DBP)\>100 mm Hg with or without anti-hypertensive medication.
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• 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.
• Patients with only locally or regionally confined disease without evidence of metastatic disease.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms; Disease

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Vicente Valero, MD/Professor, Breast Medical Oncology
• Organization: The University of Texas (UT) MD Anderson Cancer Center

vvalero@mdanderson.org

713-792-7734

Study Officials

• Vicente Valero, MD

  M.D. Anderson 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: SPONSOR

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 17, 2010
• Study Start: January 27, 2012
• Primary Completion: November 25, 2015
• Study Completion: November 25, 2015
• Last Updated: July 30, 2019
• Results First Posted: February 2, 2017

Record last verified: 2019-07

Locations

US (1)