Clinical Trials /

Romidepsin and Abraxane in Treating Patients With Metastatic Inflammatory Breast Cancer

NCT01938833

Description:

This phase I/II trial studies the side effects and best dose of romidepsin when given together with paclitaxel albumin-stabilized nanoparticle formulation and to see how well they work in treating patients with metastatic inflammatory breast cancer. Romidepsin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving romidepsin and paclitaxel albumin-stabilized nanoparticle formulation may be an effective treatment for inflammatory breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Romidepsin and Abraxane in Treating Patients With Metastatic Inflammatory Breast Cancer
  • Official Title: A Phase I/II Study of Romidepsin in Combination With Abraxane in Patients With Metastatic Inflammatory Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 13C.387
  • SECONDARY ID: 2013-035
  • NCT ID: NCT01938833

Conditions

  • HER2-negative Breast Cancer
  • Inflammatory Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer

Interventions

DrugSynonymsArms
RomidepsinIstodax, FK228, FR901228, DepsipeptideTreatment (Romidepsin and Abraxane)
AbraxaneProtein-bound paclitaxel, Paclitaxel albumin-stabilized nanoparticle formulationTreatment (Romidepsin and Abraxane)

Purpose

This phase I/II trial studies the side effects and best dose of romidepsin when given together with paclitaxel albumin-stabilized nanoparticle formulation and to see how well they work in treating patients with metastatic inflammatory breast cancer. Romidepsin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving romidepsin and paclitaxel albumin-stabilized nanoparticle formulation may be an effective treatment for inflammatory breast cancer.

Detailed Description

      PRIMARY OBJECTIVES:

        1. To assess the safety of the combination of romidepsin plus Abraxane (paclitaxel
           albumin-stabilized nanoparticle formulation) delivered weekly. (Phase I)

        2. To determine the maximum tolerated dose (MTD) of romidepsin with full dose weekly
           Abraxane to define a recommended phase II doses of the combination. (Phase I)

        3. To assess the progression-free survival (PFS) in patients with human epidermal growth
           factor receptor 2 (HER2) negative, newly diagnosed metastatic inflammatory breast cancer
           treated with the combination of romidepsin and Abraxane. (Phase II)

      SECONDARY OBJECTIVES:

        1. To assess the safety and tolerability of the combination of romidepsin and Abraxane.

        2. To determine the adverse event profile of the combination of romidepsin and Abraxane.

        3. To assess the overall response rate (ORR) and clinical benefit rate (CBR) in patients
           with newly recurrent inflammatory breast cancer (IBC) treated with the combination of
           romidepsin and Abraxane.

      OUTLINE: This is a phase I, dose-escalation study of romidepsin followed by a phase II study.

      Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV)
      over 30 minutes and romidepsin IV over 60 minutes on days 1, 8, and 15. Courses repeat every
      28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years,
      every 6 months for 2 years, and then annually thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (Romidepsin and Abraxane)ExperimentalPatients receive abraxane IV over 30 minutes and romidepsin IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Romidepsin
  • Abraxane

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have histologically or cytologically confirmed breast carcinoma with a
             clinical diagnosis of IBC based on the presence of inflammatory changes in the
             involved breast, such as 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 may have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension in accordance with RECIST criteria v.
             1.1 as described in detail in section 11.0 or non-measurable tumors

          3. Patients must have demonstrated metastatic disease and not received >2 lines of
             systemic therapy for metastatic disease

          4. Age > 18 years

          5. ECOG performance status 0, 1 or 2

          6. Patients must have normal organ and marrow function as defined below: a) Leukocytes >
             2,500/mcL b) Absolute neutrophil count > 1,500/mcL c) Hemoglobin > 9 g/dl d) Platelets
             > 100,000/mcL e) Total bilirubin < 1.5 mg/dl f) AST/ALT (SGOT/SGPT) < 2.5 x ULN g)
             Alkaline Phosphatase < 2.5 x ULN (unless bone metastasis is present in the absence of
             liver metastasis, in which case 3.0 x ULN would be acceptable. h) Serum magnesium >
             1.8 mg/dL i) Serum creatinine < 1.5 mg/dl j) Serum potassium > 3.8 mmol/L

          7. Tumor negative for HER2 expression (0 or 1+ by IHC) or negative FISH testing

          8. Patients must have a life expectancy of at least 12 weeks

          9. Patients must be recovered from the effects of any prior surgery, radiotherapy, or
             other antineoplastic therapy

         10. Patients must have < Grade 2 pre-existing peripheral neuropathy per CTCAE

         11. Women of childbearing potential and sexually active males must use an effective
             contraception method during treatment and for three months after completing treatment

         12. Negative serum or urine β-hCG pregnancy test at screening, performed no more than 72
             hours prior to treatment initiation; for patients of childbearing potential

         13. Ability to understand and willingness to sign a written informed consent and HIPAA
             consent document

        Exclusion Criteria:

          1. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study or those who have not recovered from adverse event from agents administered
             more than 4 weeks earlier

          2. Patients may not be receiving any other investigational agents or active
             anti-neoplastic therapies

          3. Patients who have previously received romidepsin or Abraxane

          4. Patients with untreated or uncontrolled brain metastases or leptomeningeal disease

          5. Patients with known hypersensitivity to any of the components of romidepsin or who
             have had hypersensitivity reactions to paclitaxel

          6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          7. Any known cardiac abnormalities such as:

               1. Congenital long QT syndrome

               2. QTc interval ≥ 500 milliseconds

               3. Myocardial infarction within 6 months of C1D1. Subjects with a history of
                  myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic
                  and have had a negative cardiac risk assessment (treadmill stress test, nuclear
                  medicine stress test, or stress echocardiogram) since the event may participate

               4. Other significant EKG abnormalities including 2nd degree atrio-ventricular (AV)
                  block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50
                  beats/min)

               5. Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see
                  Appendix III) In any patient in whom there is doubt, the patient should have a
                  stress imaging study and, if abnormal, angiography to define whether or not CAD
                  is present

               6. An EKG recorded at screening showing evidence of cardiac ischemia (ST depression
                  depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any
                  doubt, the patient should have a stress imaging study and, if abnormal,
                  angiography to define whether or not CAD is present

               7. Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class
                  II to IV definitions (see Appendix IV) and/or known ejection fraction <40% by
                  MUGA or <50% by echocardiogram and/orMRI

               8. A known history of sustained ventricular tachycardia (VT), ventricular
                  fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently
                  addressed with an automatic implantable cardioverter defibrillator (AICD)

               9. Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or
                  other causes

              10. Uncontrolled hypertension, i.e., blood pressure (BP) of ≥ 160/95; patients who
                  have a history of hypertension controlled by medication must be on a stable dose
                  (for at least one month) and meet all other inclusion criteria

              11. Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable
                  doses of beta-blockers)

              12. Patients taking drugs leading to significant QT prolongation (See Appendix I:
                  Medications That May Cause QTc Prolongation)

              13. Concomitant use of CYP3A4 inhibitors (see Appendix II)

          8. Patients with known HIV, hepatitis B or C (However, if patients have previously been
             treated for hepatitis B or C and have undetectable viral loads, they can be considered
             eligible for trial)

          9. Pregnant or breast feeding. Refer to section 4.4 for further detail

         10. Patients with any other medical or psychological condition deemed by the investigator
             to be likely to interfere with a patient's ability to sign informed consent, cooperate
             and participate in the study, or interfere with the interpretation of the results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum-Tolerated Dose of Romidepsin (Phase I)
Time Frame:28 days
Safety Issue:
Description:Determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0

Secondary Outcome Measures

Measure:Incidence of Adverse Events, Graded According to NCI CTCAE Version 4.0
Time Frame:Up to 30 days
Safety Issue:
Description:Summary tables of grade 2, 3, and 4 toxicities, adverse events (AE), and serious adverse events (SAE) will be generated at the conclusion of the study as well as at the conclusion of phase I study and after 15 patients have been collected on at the interim evaluation time point of the phase 2 part of the study.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 5 years
Safety Issue:
Description:The 95% confidence intervals should be provided.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 5 years
Safety Issue:
Description:The 95% confidence intervals should be provided.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

Last Updated

December 4, 2017