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HER2-negative Breast CancerPhase 1/2NCT01938833

Romidepsin and Abraxane in Treating Patients With Metastatic Inflammatory Breast Cancer

A Phase 1/2 study testing Romidepsin and Abraxane in people with HER2-negative Breast Cancer and Inflammatory Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Romidepsin and Abraxane
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Apr 2014to 8 Dec 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)
  • Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
  • 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
  • Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
  • Patients taking drugs leading to significant QT prolongation (See Appendix I: Medications That May Cause QTc Prolongation)
  • Concomitant use of CYP3A4 inhibitors (see Appendix II)
  • 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)
  • Pregnant or breast feeding. Refer to section 4.4 for further detail
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase I/II Study of Romidepsin in Combination With Abraxane in Patients With Metastatic Inflammatory Breast Cancer

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.

Read the 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.

Being tested
Romidepsin, Abraxane
Medical subject headings
Inflammatory Breast Neoplasms, Breast Neoplasms, Male, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RomidepsinDrug

    Also called Istodax, FK228, FR901228, Depsipeptide

  • AbraxaneDrug

    Also called Protein-bound paclitaxel, Paclitaxel albumin-stabilized nanoparticle formulation

Study groups in NCT01938833
Study groupRoleWhat they receive
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.
Receives: Drug: Romidepsin; Drug: Abraxane

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 28 days

  2. Progression-Free Survival (PFS)

    Measured: 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)
  1. Incidence of Adverse Events, Graded According to NCI CTCAE Version 4.0

    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.

    Measured: Up to 30 days

  2. Overall Response Rate (ORR)

    The 95% confidence intervals should be provided.

    Measured: Up to 5 years

  3. Clinical Benefit Rate (CBR)

    The 95% confidence intervals should be provided.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2013 (estimated)
  2. Study startApr 2014
  3. Primary completion18 Aug 2016
  4. Study completion8 Dec 2016

Why it stopped: Closed by Sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01938833
Sponsor's protocol ID
13C.387
Other IDs
2013-035, JT 2987
Status last verified
May 2025
First submitted
5 Sep 2013
Last updated
16 May 2025
Data monitoring committee
Yes

Publications

  • Blum JL, Savin MA, Edelman G, Pippen JE, Robert NJ, Geister BV, Kirby RL, Clawson A, O'Shaughnessy JA. Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes. Clin Breast Cancer. 2007 Dec;7(11):850-6. doi: 10.3816/CBC.2007.n.049.

    PubMed 18269774
  • Chang H, Jeung HC, Jung JJ, Kim TS, Rha SY, Chung HC. Identification of genes associated with chemosensitivity to SAHA/taxane combination treatment in taxane-resistant breast cancer cells. Breast Cancer Res Treat. 2011 Jan;125(1):55-63. doi: 10.1007/s10549-010-0825-z. Epub 2010 Mar 12.

    PubMed 20224928
  • Chang H, Rha SY, Jeung HC, Jung JJ, Kim TS, Kwon HJ, Kim BS, Chung HC. Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells. J Cancer Res Clin Oncol. 2010 Dec;136(12):1901-13. doi: 10.1007/s00432-010-0849-0. Epub 2010 Mar 9.

    PubMed 20217129
  • Chang S, Parker SL, Pham T, Buzdar AU, Hursting SD. Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992. Cancer. 1998 Jun 15;82(12):2366-72.

    PubMed 9635529
  • Chen MY, Liao WS, Lu Z, Bornmann WG, Hennessey V, Washington MN, Rosner GL, Yu Y, Ahmed AA, Bast RC Jr. Decitabine and suberoylanilide hydroxamic acid (SAHA) inhibit growth of ovarian cancer cell lines and xenografts while inducing expression of imprinted tumor suppressor genes, apoptosis, G2/M arrest, and autophagy. Cancer. 2011 Oct 1;117(19):4424-38. doi: 10.1002/cncr.26073.

    PubMed 21491416
  • Cristofanilli M, Buzdar AU, Hortobagyi GN. Update on the management of inflammatory breast cancer. Oncologist. 2003;8(2):141-8. doi: 10.1634/theoncologist.8-2-141.

    PubMed 12697939
  • Colpaert CG, Vermeulen PB, Benoy I, Soubry A, van Roy F, van Beest P, Goovaerts G, Dirix LY, van Dam P, Fox SB, Harris AL, van Marck EA. Inflammatory breast cancer shows angiogenesis with high endothelial proliferation rate and strong E-cadherin expression. Br J Cancer. 2003 Mar 10;88(5):718-25. doi: 10.1038/sj.bjc.6600807.

    PubMed 12618881
  • Desai N, Trieu V, Yao R, et al. Increased transport of nanoparticle albumin-bound paclitaxel (ABI-007) by endothelial gp60-mediated caveolar transcytosis: a pathway inhibited by Taxol. Eur J Cancer Suppl. 2004;2:182.

  • Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. doi: 10.1200/JCO.2008.18.5397. Epub 2009 May 26.

    PubMed 19470941
  • Kim H, Kim SN, Park YS, Kim NH, Han JW, Lee HY, Kim YK. HDAC inhibitors downregulate MRP2 expression in multidrug resistant cancer cells: implication for chemosensitization. Int J Oncol. 2011 Mar;38(3):807-12. doi: 10.3892/ijo.2010.879. Epub 2010 Dec 17.

    PubMed 21170509
  • Hoshino I, Matsubara H, Akutsu Y, Nishimori T, Yoneyama Y, Murakami K, Komatsu A, Sakata H, Matsushita K, Ochiai T. Gene expression profiling induced by histone deacetylase inhibitor, FK228, in human esophageal squamous cancer cells. Oncol Rep. 2007 Sep;18(3):585-92.

    PubMed 17671705
  • Lassen U, Molife LR, Sorensen M, Engelholm SA, Vidal L, Sinha R, Penson RT, Buhl-Jensen P, Crowley E, Tjornelund J, Knoblauch P, de Bono JS. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours. Br J Cancer. 2010 Jun 29;103(1):12-7. doi: 10.1038/sj.bjc.6605726. Epub 2010 Jun 15.

    PubMed 20588278
  • Low JA, Berman AW, Steinberg SM, Danforth DN, Lippman ME, Swain SM. Long-term follow-up for locally advanced and inflammatory breast cancer patients treated with multimodality therapy. J Clin Oncol. 2004 Oct 15;22(20):4067-74. doi: 10.1200/JCO.2004.04.068.

    PubMed 15483018
  • Modesitt SC, Sill M, Hoffman JS, Bender DP; Gynecologic Oncology Group. A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2008 May;109(2):182-6. doi: 10.1016/j.ygyno.2008.01.009. Epub 2008 Mar 4.

    PubMed 18295319
  • Nguyen DM, Sam K, Tsimelzon A, Li X, Wong H, Mohsin S, Clark GM, Hilsenbeck SG, Elledge RM, Allred DC, O'Connell P, Chang JC. Molecular heterogeneity of inflammatory breast cancer: a hyperproliferative phenotype. Clin Cancer Res. 2006 Sep 1;12(17):5047-54. doi: 10.1158/1078-0432.CCR-05-2248.

    PubMed 16951220

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Romidepsin and Abraxane in people with HER2-negative Breast Cancer and Inflammatory Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum-Tolerated Dose of Romidepsin (Phase I) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01938833, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.

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