Romidepsin and Abraxane in Treating Patients With Metastatic Inflammatory Breast Cancer

NCT01938833 | Terminated Phase 1 Results DMC

• 3 other identifiers: 13C.3872013-035JT 2987
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum-Tolerated Dose of Romidepsin (Phase I)

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

  28 days

• 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 Outcomes (3)

• Incidence of Adverse Events, Graded According to NCI CTCAE Version 4.0

  Up to 30 days

• Overall Response Rate (ORR)

  Up to 5 years

• Clinical Benefit Rate (CBR)

  Up to 5 years

Study Arms (1)

Treatment (Romidepsin and Abraxane)

EXPERIMENTAL

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; Drug: Abraxane

Interventions

Romidepsin DRUG

Also known as: Istodax, FK228, FR901228, Depsipeptide

Treatment (Romidepsin and Abraxane)

Abraxane DRUG

Also known as: Protein-bound paclitaxel, Paclitaxel albumin-stabilized nanoparticle formulation

Treatment (Romidepsin and Abraxane)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• Patients must have demonstrated metastatic disease and not received \>2 lines of systemic therapy for metastatic disease
• Age \> 18 years
• ECOG performance status 0, 1 or 2
• 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
• Tumor negative for HER2 expression (0 or 1+ by IHC) or negative FISH testing
• Patients must have a life expectancy of at least 12 weeks
• Patients must be recovered from the effects of any prior surgery, radiotherapy, or other antineoplastic therapy
• Patients must have \< Grade 2 pre-existing peripheral neuropathy per CTCAE
• Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment
• 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
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document

You may not qualify if:

• 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
• Patients may not be receiving any other investigational agents or active anti-neoplastic therapies
• Patients who have previously received romidepsin or Abraxane
• Patients with untreated or uncontrolled brain metastases or leptomeningeal disease
• Patients with known hypersensitivity to any of the components of romidepsin or who have had hypersensitivity reactions to paclitaxel
• 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
• Any known cardiac abnormalities such as:
• Congenital long QT syndrome
• QTc interval ≥ 500 milliseconds
• 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
• 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)
• 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
• 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
• 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
• 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)

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Celgene Corporation: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (23)

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Related Links

• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms, Male; Breast Neoplasms

Interventions

romidepsin; Depsipeptides; Albumin-Bound Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Dr. Maysa Abu-Khalaf
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University

maysa.abu-khalaf@jefferson.edu

215 503-4685

Study Officials

• Maysa Abu-khalaf, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: April 1, 2014
• Primary Completion: August 18, 2016
• Study Completion: December 8, 2016
• Last Updated: May 16, 2025
• Results First Posted: September 29, 2017

Record last verified: 2025-05

Locations

US (1)