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Romidepsin and Abraxane in Treating Patients With Metastatic Inflammatory Breast Cancer

Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
Overall Status
Terminated
CT.gov ID
NCT01938833
Collaborator
Celgene Corporation (Industry)
9
Enrollment
1
Location
1
Arm
32.3
Actual Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
9 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Study of Romidepsin in Combination With Abraxane in Patients With Metastatic Inflammatory Breast Cancer
Actual Study Start Date :
Apr 1, 2014
Actual Primary Completion Date :
Aug 18, 2016
Actual Study Completion Date :
Dec 8, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (Romidepsin and Abraxane)

Patients 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.

Drug: Romidepsin
Other Names:
  • Istodax
  • FK228
  • FR901228
  • Depsipeptide

    • Drug: Abraxane
    Other Names:
  • Protein-bound paclitaxel
  • Paclitaxel albumin-stabilized nanoparticle formulation

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum-Tolerated Dose of Romidepsin (Phase I) [28 days]

      Determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0

    2. Progression-Free Survival (PFS) [The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years]

    Secondary Outcome Measures

    1. Incidence of Adverse Events, Graded According to NCI CTCAE Version 4.0 [Up to 30 days]

      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.

    2. Overall Response Rate (ORR) [Up to 5 years]

      The 95% confidence intervals should be provided.

    3. Clinical Benefit Rate (CBR) [Up to 5 years]

      The 95% confidence intervals should be provided.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

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

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

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

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

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

    6. 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

    7. 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:

    8. Congenital long QT syndrome

    9. QTc interval ≥ 500 milliseconds

    10. 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

    11. 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)

    12. 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

    13. 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

    14. 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

    15. 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)

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

    17. 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

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

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

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

    21. 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)

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

    23. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Thomas Jefferson University Philadelphia Pennsylvania United States 19107

    Sponsors and Collaborators

    • Sidney Kimmel Cancer Center at Thomas Jefferson University
    • Celgene Corporation

    Investigators

    • Principal Investigator: Maysa Abu-khalaf, MD, Thomas Jefferson University

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Sidney Kimmel Cancer Center at Thomas Jefferson University
    ClinicalTrials.gov Identifier:
    NCT01938833
    Other Study ID Numbers:
    • 13C.387
    • 2013-035
    First Posted:
    Sep 10, 2013
    Last Update Posted:
    Dec 28, 2017
    Last Verified:
    Dec 1, 2017
    Additional relevant MeSH terms:
    Breast Neoplasms
    Breast Neoplasms, Male
    Inflammatory Breast Neoplasms
    Paclitaxel
    Albumin-Bound Paclitaxel
    Romidepsin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    Period Title: Overall Study
    STARTED 9
    COMPLETED 9
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    Overall Participants 9
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    51.6
    (9.33)
    Sex: Female, Male (Count of Participants)
    Female
    9
    100%
    Male
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    9
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    9
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    9
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum-Tolerated Dose of Romidepsin (Phase I)
    Description Determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    Data were not collected and the Outcome will never be analyzed.
    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    Measure Participants 0
    2. Primary Outcome
    Title Progression-Free Survival (PFS)
    Description
    Time Frame The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Data were not collected and the Outcome will never be analyzed
    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    Measure Participants 0
    3. Secondary Outcome
    Title Incidence of Adverse Events, Graded According to NCI CTCAE Version 4.0
    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.
    Time Frame Up to 30 days

    Outcome Measure Data

    Analysis Population Description
    Data were not collected and the Outcome will never be analyzed.
    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    Measure Participants 0
    4. Secondary Outcome
    Title Overall Response Rate (ORR)
    Description The 95% confidence intervals should be provided.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Data were not collected and the Outcome will never be analyzed.
    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    Measure Participants 0
    5. Secondary Outcome
    Title Clinical Benefit Rate (CBR)
    Description The 95% confidence intervals should be provided.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Data were not collected and the Outcome will never be analyzed.
    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    Measure Participants 0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Treatment (Romidepsin and Abraxane)
    Arm/Group Description Patients 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
    All Cause Mortality
    Treatment (Romidepsin and Abraxane)
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Treatment (Romidepsin and Abraxane)
    Affected / at Risk (%) # Events
    Total 2/7 (28.6%)
    Infections and infestations
    Fever 1/7 (14.3%) 2
    Renal and urinary disorders
    Catheter related Infection 1/7 (14.3%) 1
    Skin and subcutaneous tissue disorders
    Rash Acneiform 1/7 (14.3%) 1
    Other (Not Including Serious) Adverse Events
    Treatment (Romidepsin and Abraxane)
    Affected / at Risk (%) # Events
    Total 7/9 (77.8%)
    Blood and lymphatic system disorders
    Alanine Aminotransferase Increased 3/9 (33.3%) 10
    Alkaline phosphatase Increased 2/9 (22.2%) 2
    Anemia 7/9 (77.8%) 18
    Aspartate Aminotransferase increased 1/9 (11.1%) 1
    Epistaxis 1/9 (11.1%) 1
    Hematoma 1/9 (11.1%) 1
    Hypercalcemia 1/9 (11.1%) 1
    Hyperglycemia 6/9 (66.7%) 14
    Hyperphosphatemia 1/9 (11.1%) 2
    Hypocalcemia 2/9 (22.2%) 2
    Hypokalemia 1/9 (11.1%) 2
    Hyponatremia 2/9 (22.2%) 4
    Hypophosphatemia 1/9 (11.1%) 2
    INR increased 1/9 (11.1%) 2
    Lymphocyte Count Decreased 1/9 (11.1%) 6
    Platelet Count decreased 1/9 (11.1%) 1
    Ear and labyrinth disorders
    Tinnitus 1/9 (11.1%) 1
    Endocrine disorders
    LDH increased 1/9 (11.1%) 1
    Eye disorders
    Blurred Vision 1/9 (11.1%) 2
    Eye disorders 2/9 (22.2%) 4
    Gastrointestinal disorders
    Constipation 4/9 (44.4%) 4
    Diarrhea 2/9 (22.2%) 2
    Dyspepsia 1/9 (11.1%) 1
    Gastrointestinal other symptoms 1/9 (11.1%) 1
    Gastrointestinal Pain 1/9 (11.1%) 1
    Heart Burn 1/9 (11.1%) 1
    Nausea 4/9 (44.4%) 6
    Vomiting 4/9 (44.4%) 4
    General disorders
    Body Aches 1/9 (11.1%) 1
    Bone Pain 1/9 (11.1%) 1
    Chills 1/9 (11.1%) 1
    Dizziness 4/9 (44.4%) 4
    Dry mouth 1/9 (11.1%) 1
    Dsygeusia 3/9 (33.3%) 4
    Edema in the Limbs 4/9 (44.4%) 9
    Fatigue 5/9 (55.6%) 11
    Headaches 5/9 (55.6%) 5
    Malaise 1/9 (11.1%) 1
    Mucositis oral 1/9 (11.1%) 1
    Pain 7/9 (77.8%) 17
    Right Foot Pain 1/9 (11.1%) 1
    Right leg pain 1/9 (11.1%) 1
    Runny Nose 1/9 (11.1%) 1
    Shoulder pain 1/9 (11.1%) 1
    Sore Throat 1/9 (11.1%) 1
    Toothache 1/9 (11.1%) 2
    Immune system disorders
    Alopecia 5/9 (55.6%) 6
    Infections and infestations
    Fever 1/9 (11.1%) 1
    Flu like symptoms-Cold 1/9 (11.1%) 1
    Lower Jaw Infection 1/9 (11.1%) 1
    Neutrophil count decreased 4/9 (44.4%) 7
    Sinusitis 1/9 (11.1%) 1
    White blood cell decreased 5/9 (55.6%) 12
    Wound - Right Arm 1/9 (11.1%) 1
    Musculoskeletal and connective tissue disorders
    Lower Back Spasm 1/9 (11.1%) 1
    Lump 1/9 (11.1%) 1
    Tightness 2/9 (22.2%) 9
    Nervous system disorders
    Insomnia 2/9 (22.2%) 2
    Neuropathy 4/9 (44.4%) 7
    Numbness 1/9 (11.1%) 1
    Sensory Neuropathy 2/9 (22.2%) 2
    Tremor 1/9 (11.1%) 1
    Psychiatric disorders
    Anorexia 1/9 (11.1%) 1
    Anxiety 1/9 (11.1%) 1
    Depression 3/9 (33.3%) 3
    Negative Thoughts 1/9 (11.1%) 1
    Renal and urinary disorders
    Hematuria 1/9 (11.1%) 2
    Interstitial Cystitis 1/9 (11.1%) 1
    Urine Culture Growth 1/9 (11.1%) 2
    Reproductive system and breast disorders
    Irregular Menstruation 1/9 (11.1%) 1
    Vaginal Dryness 1/9 (11.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 3/9 (33.3%) 5
    Dyspenea 1/9 (11.1%) 2
    Pleural Effusion 1/9 (11.1%) 1
    Skin and subcutaneous tissue disorders
    Flushing 1/9 (11.1%) 1
    Pruritus 2/9 (22.2%) 2
    Rash 1/9 (11.1%) 2
    Skin Disorder - Hole 1/9 (11.1%) 1
    Skin Infection-Cellulitis 1/9 (11.1%) 1
    Skin Peeling 1/9 (11.1%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Maysa Abu-Khalaf
    Organization Sidney Kimmel Cancer Center at Thomas Jefferson University
    Phone 215 503-4685
    Email maysa.abu-khalaf@jefferson.edu
    Responsible Party:
    Sidney Kimmel Cancer Center at Thomas Jefferson University
    ClinicalTrials.gov Identifier:
    NCT01938833
    Other Study ID Numbers:
    • 13C.387
    • 2013-035
    First Posted:
    Sep 10, 2013
    Last Update Posted:
    Dec 28, 2017
    Last Verified:
    Dec 1, 2017