Study Drug Administration:
Each study cycle is 4 weeks.
If you are found to be eligible to take part in this study, you will take nintedanib
capsules by mouth 2 times each day. Each dose should be about 12 hours apart, at about the
same times every day. The capsules should be swallowed whole with about a cup (8 ounces) of
water within 30 minutes after eating a meal.
If you forget to take the capsules and it has been more than 2 hours since you were
scheduled to take the dose, you should skip that dose and take the next dose as scheduled.
Do not double the next dose to "make up" the missed one.
You will be given a study drug diary to write down when you took each dose of study drug.
You will need to bring back any empty or partially used bottles of study drug, along with
any leftover study drug, with you to the clinic at each cycle.
If you experience side effects, you will be given standard drugs to help decrease the
symptoms of the side effects. You may ask the study staff for information about how the
drugs are given and their risks.
All tests and procedures below will be performed before your dose of study drug.
On Day 1 of Cycles 1-6 and then every other cycle after Day 1 of Cycle 8 (Cycles 10, 12, 14,
and so on):
- You will have a physical exam. On Cycles 4 and 6, this physical exam may be performed
at a local clinic or doctor's office. The results will be sent to the study doctor for
- Blood (about 2 tablespoons) will be drawn for routine tests. On Cycles 4 and 6, you may
have this blood drawn performed at a local clinic or doctor's office. The results will
be sent to the study doctor for review.
On Day 1 of Cycle 3, blood (about 2 tablespoons) will also be drawn for biomarker testing.
On Day 1 of Cycles 3, 5, 8, and then every even numbered cycle after that (Cycles 10, 12, 14
and so on):
- If the doctor thinks it is needed, photographs will be taken of any areas affected by
- If the doctor thinks it is needed, you will have an x-ray, ultrasound, CT scan, PET/CT
scan, and/or a bone scan to check the status of the disease.
At any point that the doctor thinks it is needed, you will have an EKG, ECHO, and/or MUGA
scan. You may have any of the above tests/procedures repeated as well, if the doctor thinks
it is needed, to check on your health.
Length of Study:
You may continue taking the study drug for up to 2 years. You will no longer be able to
take the study drug if the disease gets worse, if intolerable side effects occur, or if you
are unable to follow study directions.
Your participation on the study will be over after you have completed the follow-up period.
Within 14 days after the last study visit:
- You will have a physical exam.
- 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 the disease.
- If the doctor thinks it is needed, you will have an x-ray, CT scan, PET/CT scan, and/or
a bone scan to check the status of the disease.
- If the doctor thinks it is needed, you will have an EKG and either an ECHO or MUGA
You will be called by a member of the study staff every 3 months for up to 1 year after your
end-of-treatment visit and asked how you are doing. These calls should last about 2
This is an investigational study. Nintedanib is commercially available and FDA approved for
the treatment of certain types of lung disease. Its use in this study is investigational.
The study doctor can explain how the study drug is designed to work.
Up to 44 participants will be enrolled in this study. All will take part at MD Anderson.
1. Patients are 18 years of age or older
2. Patients are female or male.
3. 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 at diagnosis.
4. Have confirmed distant metastasis with or without local recurrence.
5. Have negative HER2 expression by IHC (defined as 0 or1+), or FISH. If HER2 is 2+,
negative HER2 expression must be confirmed by FISH.
6. Estimated life expectancy of at least 3 months
7. Have ECOG performance status score 0-2
8. Have received 2 or more chemotherapies for local recurrence or metastatic disease and
9. Signed and dated written informed consent prior to admission to the study
10. If Patients have been treated with anti-VEGF agents, such as Bevacizumab, last dose
must be >/= 4 weeks.
11. Have tissues from a biopsy, or have up to 20 unstained slides available from archived
metastatic tissue block for biomarker evaluation
12. Patients are able to swallow and retain oral medication
1. Patients have an active infection and require IV or oral antibiotics.
2. Patients have 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) or multiple gated acquisition scan (MUGA) < 45%
3. 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) > NYHA II, 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, serious cardiac
arrhythmia, pericardial effusion
4. History of gastrointestinal disorders (medical disorders or extensive surgery) which
may interfere with the absorption of the study drug as determined by the
5. 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 as determined by the investigator.
6. Patients with only locally or regionally confined disease without evidence of
7. Prior treatment with BIBF 1120 or any other VEGFR inhibitor within 4 weeks
8. Known hypersensitivity to the trial drugs , to their excipients or to contrast media
9. Chemotherapy, hormonal therapy, radiotherapy (except for brain and extremities) or
immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase
inhibitors within the past 4 weeks prior to treatment with the trial drug
10. Persistence of toxicity from previous chemo and/or radiotherapy > grade 2.
11. Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment
with radiotherapy, symptomatic, requiring treatment with anti-convulsants;
dexamethasone therapy will be allowed if administered as stable dose for at least one
month before randomisation).
12. Leptomeningeal disease
13. Radiographic evidence of cavitary or necrotic tumors
14. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of
major blood vessels
15. Treatment with other investigational drugs or treatment in another clinical trial
within the past 4 weeks before start of therapy or concomitantly with the trial
16. Therapeutic anticoagulation( except low-dose heparin and/or heparin flush as needed
for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy
(except for low-dose therapy with acetylsalicylic acid < 325mg per day
17. Major injuries within the past 10 days prior to start of study treatment with
incomplete wound healing and/or planned surgery during the on-treatment study period
18. History of clinically significant haemorrhagic or thromboembolic event in the past 6
19. Known inherited predisposition to bleeding or thrombosis
20. Proteinuria CTCAE grade 2 or greater
21. Creatinine >/= 1.5 x ULN or GFR < 45 ml/min
22. Hepatic function: total bilirubin outside of normal limits; ALT or AST >1.5 x ULN in
pts without liver metastasis. For Pts with liver metastasis: total bilirubin outside
of normal limits, ALT or AST >2.5 x ULN
23. Coagulation parameters: International normalised ratio ( INR) > 2, prothrombin time
(PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN
24. Absolute neutrophil count ( ANC) < 1500/ml, platelets < 100000/ml, Haemoglobin < 9.0
25. Other malignancies within the past 5 years other than basal cell skin cancer or
carcinoma in situ of the cervix
26. Known history of active or chronic hepatitis C and/or B infection
27. Serious illness or concomitant non-oncological disease such as neurologic,
psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration and in the judgment of the investigator would make the
patient inappropriate for entry into the study.
28. Patients who are sexually active and unwilling to use a medically acceptable method
of contraception (e.g. such as implants, injectables, combined oral contraceptives,
some intrauterine devices or vasectomized partner for participating females) during
the trial and for at least three months after end of active therapy (Contraception in
patients with preserved reproductive capacity, patients will be considered to be of
childbearing potential unless surgically sterilised by hysterectomy or bilateral
tubal ligation/salpingectomy, or post-menopausal for at least two years.)
29. Patients with child bearing potential must have a negative pregnancy test (urine or
serum) prior to study treatment
30. Psychological, familial, sociological or geographical factors potentially hampering
compliance with the study protocol and follow-up schedule
31. Active alcohol or drug abuse
32. Significant weight loss (> 10% of BW) within past 6 months prior to inclusion into
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both