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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


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

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


The Study Drug:

Dovitinib is designed bind to a protein on the surface of cancer cells called the FGF
receptor. This may slow the growth of cancer cells or kill cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take dovitinib by mouth
each day for 5 days and have a 2-day rest period (5 days on/2 days off schedule). The first
dose of each week is Day 1. You should take dovitinib in the morning with a glass (about 8
ounces) of water at least 1 hour before or at least 2 hours after eating. It is important
that you take the study drug at about the same time every day.

If you forget to take a dose of the study drug as scheduled, or take a dose during your
2-day rest period, you should follow the guidelines below or call your study staff:

- If you take a dose on Day 6, then you will rest on Day 7 and start taking the drug on
Day 1.

- If you take a dose on Day 7, then you will skip Day 1 the next schedule and start
dosing on Day 2.

- If you take a dose on Day 6 and Day 7, then you will skip Days 1 and 2 of the next
schedule and start dosing on Day 3.

- If you missed a dose on Days 1, 2, 3, or 4, you should restart the next dosing day and
rest on Days 6 and 7.

- If you missed a dose on Day 5, you should rest on Days 6 and 7, and restart dosing on
Day 1 of the next week.

You should not take additional medications including over-the-counter products and
herbal/alternative medications during the study without asking your doctor. It is important
to avoid medications that are known to cause liver side effects.

If you experience intolerable side effects, the study doctor may give you drugs to help
control the side effects.

You should store the study drug at room temperature and out of direct sunlight. The study
drug should also be kept away from children.

About every 4 weeks, you will need to bring back your empty or partially used bottles of
study drug.

During Treatment:

At every visit, you will be asked if you have had any side effects.

Before each Cycle:

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- Blood (about 2 tablespoons) will be drawn for routine tests.

Cycle 1 around day 8 and day 22:

-Blood (about 1 tablespoon) will be drawn to check your liver function.

Before Cycle 2:

-Blood (about 1 tablespoon) will be drawn to measure the level of the study drug.

Cycle 2 around day 8:

-Blood (about 1 tablespoon) will be drawn to check your liver function.

Every 2 cycles (before Cycles 3, 5, 7, and so on):

- If the doctor thinks it is needed, photographs will be taken of your skin and any areas
affected by inflammatory breast cancer.

- If the doctor thinks it is needed, you will have x-rays, a CT scan of the chest and/or
abdomen, and/or a bone scan.

Before Cycle 3:

- If the doctor thinks it is needed, you will have a PET/CT scan to check the status of
the disease.

- Blood (about 2 tablespoons) will be drawn for biomarker testing.

If the doctor thinks it is needed, any of these tests and procedures may be performed
earlier. If the doctor thinks it is needed, you will have an ECG, ECHO, or MUGA scan to
check your heart function.

Length of Study:

You may remain on study for as long as you are benefiting. You will be taken off study
treatment if the disease gets worse or you experience intolerable side effects.

Your participation on the study will be over once you have completed the end-of-treatment
visit.

End-of-Treatment Visit:

After you are off study, you will have a end-of-treatment visit within 14 days after the
last study visit.

- You will be asked if you have had any side effects.

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- If the doctor thinks it is needed, photographs will be taken of your skin and any areas
affected by inflammatory breast cancer.

- If the doctor thinks it is needed, you will have x-rays, a CT scan of the chest and/or
abdomen, and/or a bone scan.

- If the doctor thinks it is needed, you will have an ECG and ECHO or MUGA scan to check
your heart function.

- If the doctor thinks it is needed, you will have a PET/CT scan to check the status of
the disease.

Follow-up Visits:

You will be called or e-mailed every 3 months for up to 1 year and asked how you are doing.

This is an investigational study. Dovitinib is not FDA approved or commercially available.
At this time, dovitinib is only being used in research.

Up to 33 patients will take part in this study. All will be enrolled at MD Anderson.


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

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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Response Rate

Outcome Time Frame:

6 months

Safety Issue:

Yes

Principal Investigator

Ricardo Alvarez, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0296

NCT ID:

NCT01262027

Start Date:

January 2012

Completion Date:

Related Keywords:

  • Breast Cancer
  • Metastatic inflammatory breast cancer
  • Stage IV disease
  • HER2-negative
  • Dovitinib
  • TKI258
  • Breast Neoplasms
  • Inflammatory Breast Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030