TKI258 for Metastatic Inflammatory Breast Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01262027
First received: December 15, 2010
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Dovitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of TKI258 (Dovitinib Lactate) as Salvage Therapy in Patients With Stage IV HER2-negative Inflammatory Breast Cancer (IBC) and Local or Distant Relapse

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Overall response rate (ORR) defined as percentage of patients experiencing stable disease, complete or partial response (SD, CR or PR) as defined by RECIST. A response is anyone who experiences SD, CR or PR in the first 6 months.


Secondary Outcome Measures:
  • Safety Analysis of Dovitinib [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Safety analysis evaluated by grading each adverse event (e.g., neutropenia, neurotoxicity, and CINV) according to CTCAE v4.0 and reporting the type, frequency and severity.


Estimated Enrollment: 33
Study Start Date: January 2012
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dovitinib
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
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.
Other Name: TKI258

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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: NCT01262027

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Principal Investigator: Ricardo Alvarez, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01262027     History of Changes
Other Study ID Numbers: 2010-0296, NCI-2011-00299
Study First Received: December 15, 2010
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Metastatic inflammatory breast cancer
Stage IV disease
HER2-negative
Dovitinib
TKI258

Additional relevant MeSH terms:
Breast Neoplasms
Inflammatory Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 23, 2014