Clinical Trials /

Nintedanib For HER2-Negative Metastatic Inflammatory Breast Cancer (MIBC)

NCT02389764

Description:

The goal of this clinical research study is to learn if Ofev® (nintedanib, also called BIBF1120) can help to control IBC. The safety of this drug will also be studied. 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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nintedanib For HER2-Negative Metastatic Inflammatory Breast Cancer (MIBC)
  • Official Title: A Phase II Study of BIBF1120 (Nintedanib) for Patients With Metastatic HER2-Negative Inflammatory Breast Cancer (IBC)

Clinical Trial IDs

  • ORG STUDY ID: 2014-0464
  • SECONDARY ID: NCI-2015-00506
  • NCT ID: NCT02389764

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
BIBF 1120NintedanibBIBF 1120

Purpose

The goal of this clinical research study is to learn if Ofev® (nintedanib, also called BIBF1120) can help to control IBC. The safety of this drug will also be studied. 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.

Detailed Description

      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.

      Study Visits:

      All tests and procedures below will be performed before your dose of study drug.

      On Day 1 of every cycle:

        -  You will have a physical exam.

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

      On Day 1 of Cycles 1-7 and then every odd-numbered cycle after that (Cycles 9,11, 13, and so
      on), the physical exam and blood draw will be performed at MD Anderson . On Day 1 of Cycles 8
      and then every even-numbered cycle after that (Cycles 10, 12, 14, and so on), the physical
      exam and blood draw may be performed at a local clinic or doctor's office and the results
      will be sent to the study doctor for review. The study doctor will discuss this option with
      you.

      On Day 1 of Cycle 3, blood (about 2 tablespoons) will also be drawn for biomarker testing.

      On Day 1 of Cycles 3, 5, 7, and then every odd numbered cycle after that (Cycles 9, 11, 13,
      and so on):

        -  If the doctor thinks it is needed, photographs will be taken of any areas affected by
           the disease.

        -  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.

      End-of-Treatment Visit:

      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, ultrasound, 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 scan.

      Follow-up Visits:

      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 minutes.
    

Trial Arms

NameTypeDescriptionInterventions
BIBF 1120ExperimentalInitial dose of BIBF 1120 is 200 mg twice daily orally for a 28 day cycle. Participant called by a member of the study staff every 3 months for up to 1 year after end-of-treatment visit. Participant called by a member of the study staff every 3 months for up to 1 year after end-of-treatment visit.
  • BIBF 1120

Eligibility Criteria

        Inclusion Criteria:

          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. Patients may undergo an optional biopsy of the metastatic disease at baseline and
             after 2 cycles of BIBF-1120.

          7. Estimated life expectancy of at least 3 months

          8. Have ECOG performance status score 0-2

          9. Have received at least one any prior treatment for local recurrence or metastatic
             disease and have relapsed.

         10. Signed and dated written informed consent prior to admission to the study

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

         12. Have tissues from a biopsy, or have up to 20 unstained slides available from archived
             metastatic tissue block for biomarker evaluation

         13. Patients are able to swallow and retain oral medication

        Exclusion Criteria:

          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%; d). pericardial effusion

          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),

          4. Uncontrolled hypertension defined by an SBP>150 and/or a DBP>100 mm Hg with or without
             anti-hypertensive medication

          5. History of gastrointestinal disorders (medical disorders or extensive surgery) which
             may interfere with the absorption of the study drug as determined by the investigator.

          6. 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.

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

          8. Prior treatment with BIBF 1120 or any other VEGFR inhibitor within 4 weeks

          9. Known hypersensitivity to the trial drugs , to their excipients or to contrast media

         10. 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

         11. Persistence of toxicity from previous chemo and/or radiotherapy > grade 2.

         12. 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).

         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
             months

         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
             g/dl

         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 the
             trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Benefit Rate (Complete Response [CR], Partial Response [PR] or Stable Disease [SD] Date) of BIBF 1120 (Nintedanib) in Patients With HER2-negative Metastatic Inflammatory Breast Cancer (IBC).
Time Frame:2 years
Safety Issue:
Description:Clinical benefit defined as participants who achieve CR or PR within 3 months post-treatment, or participants who experience SD for at least three months post-treatment. Clinical benefit rate determined by RECIST 1.1 version." PATHOLOGICAL CR: No evidence of residual invasive tumor, including no residual tumor in the axillary lymph nodes. PR is defined as 30% or greater decrease for a minimum of 4 weeks in the measurable lesion as determined by the product of the perpendicular diameters of the lesion. Every lesion should not regress to qualify as a PR. However, if any lesion progresses or if new lesions appear, the response cannot be classified as a (PR). Minor Response [MR] Decreases in tumor masses insufficient to qualify as a partial remission, i.e. <50%. SD between MR and PD. PD increase in the size by 25% of any measured lesion from baseline. Appearance of new lesions will also constitute increasing disease. Mixed responses will be considered PD.

Secondary Outcome Measures

Measure:Safety Measures of BIBF 1120 in Terms of Type, Frequency and Severity of Adverse Event According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 in Patients With Metastatic IBC.
Time Frame:2 years
Safety Issue:
Description:An adverse event (AE) is defined as any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a patient in a clinical investigation who received a pharmaceutical product. The event does not necessarily have to have a causal relationship with this treatment. All adverse events (grade 3 or higher for hematological toxicity, grade 2 or higher for non-hematological toxicity)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Breast cancer
  • Metastatic inflammatory breast cancer
  • MIBC
  • HER2-negative
  • Breast carcinoma
  • BIBF 1120
  • Nintedanib
  • Phone call

Last Updated

July 17, 2019