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Trial of Amrubicin as Second-Line Therapy in Patients With Advanced/Metastatic Refractory Urothelial Carcinoma

This study has been terminated.
(due to a development decision by the funder)
Celgene Corporation
Information provided by (Responsible Party):
Matthew Galsky, Icahn School of Medicine at Mount Sinai Identifier:
First received: April 6, 2011
Last updated: November 21, 2015
Last verified: November 2015
The primary objective of this study is to determine in subjects with metastatic measurable bladder cancer (or urothelial cancers originating elsewhere in the genitourinary tract) who have progressed on 1 prior chemotherapeutic regimen the objective response rate to treatment with amrubicin. The secondary objectives will be to evaluate progression-free survival, survival at 1 year, and the safety of amrubicin as second-line therapy in patients with metastatic urothelial carcinoma.

Condition Intervention Phase
Bladder Cancer
Drug: Amrubicin
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-Center Phase 2 Trial of Single-Agent Amrubicin as Second-Line Therapy in Patients With Advanced/Metastatic Refractory Urothelial Carcinoma

Resource links provided by NLM:

Further study details as provided by Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Objective Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: 6 weeks ]

    Response to treatment based on tumor measurements via CT chest, abdomen, and pelvis for restaging after every 2 cycles.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: Every 3 months post Amrubicin administration ]

    The median progression-free survival

    After the last dose of Amrubicin, patients will have follow-up every 3 months with a repeat CT scan of the chest, abdomen, and pelvis until the time of disease progression is documented.

  • Overall Survival [ Time Frame: 1 year ]
    The median overall survival

  • Safety as Measured by the Frequency and Type of Adverse Events as Per the Common Terminology for Adverse Events (CTCAE) Version 4.0. [ Time Frame: Day 1 of each treatment cycle; and 21 days after the last dose of amrubicin ]

Enrollment: 22
Study Start Date: February 2011
Study Completion Date: July 2015
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amrubicin
35 mg/m2/day intravenously
Drug: Amrubicin
Patients will receive 35 mg/m2/day of amrubicin intravenously for 3 consecutive days as the initial dose starting on Day 1 of a 21-day cycle for up to 6 cycles

Detailed Description:

Multiple small phase II trials exploring a variety of agents as second-line therapy for metastatic urothelial carcinoma have been performed. Overall, the most active of these agents have shown response rates of approximately 10-20% . Currently, there are no FDA approved agents for the second-line treatment of metastatic urothelial carcinoma.

The current study will explore the safety and activity of the novel anthracycline, amrubicin, as second-line chemotherapy in patients with advanced urothelial carcinoma.

The primary objective will be to evaluate the activity (as determined by objective response rate) of amrubicin as second-line chemotherapy in patients with metastatic urothelial carcinoma. The secondary objectives will be to evaluate progression-free survival, survival at 1 year, and the safety of amrubicin as second-line therapy in patients with metastatic urothelial carcinoma.

Subjects will receive amrubicin IV daily x 3 days, every 21-days, with prophylactic granulocyte colony stimulating factor. This 21-day time period is referred to as a cycle. Subjects will undergo repeat computed tomography (CT) scans after every 2 cycles. In the absence of progressive cancer, or prohibitive side effects, subjects will receive up to 6 cycles of treatment with amrubicin.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Written informed consent
  2. Age > 18 years
  3. Karnofsky performance status of ≥ 80%
  4. Histological or cytological proof of transitional cell carcinoma of the urothelial tract. The primary site may include: urethra, bladder, ureters, and renal pelvis.
  5. Progressive advanced/metastatic disease despite prior chemotherapy:

    • Patients may have received one prior chemotherapy regimen.
    • Prior chemotherapy may have been administered in the perioperative setting (neoadjuvant or adjuvant) or 1st line metastatic setting.
  6. Measurable disease according to RECIST 1.1
  7. Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
  8. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
  9. Adequate organ function including the following:

    • Adequate bone marrow reserve: absolute neutrophil count (segmented and bands) (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 mg/L,
    • Hepatic: bilirubin ≤ 1.5 x the upper limit of normal (ULN), ALT and AST ≤ 3.0 x ULN (or ≤ 5.0 x ULN in the presence of hepatic metastases)
    • Renal: serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min,
    • Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% or ≥ the lower limit of the institutional normal by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA);

Exclusion Criteria:

  1. Has had major surgery within 30 days of starting study treatment.
  2. Has active CNS metastases. Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
  3. Has a history of a prior malignancy with the exception of the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, clinically localized prostate cancer treated with definitive local therapy and without evidence of recurrent disease and without the need for androgen deprivation therapy, or other cancer for which the subject has been disease-free for at least 5 years.
  4. Has had treatment with another anticancer agent or investigational agent within 30 days prior to being registered for protocol therapy.
  5. Has had prior radiation therapy to > 25% of the bone marrow.

    • NOTE: No radiation therapy within 30 days prior to being registered for protocol therapy.
  6. Has a clinically significant infection as judged by the treating investigator.
  7. Pregnant or nursing females.
  8. Patients with known history of seropositive human immunodeficiency virus (HIV) or patients who are receiving immunosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications.
  9. History of congestive heart failure
  10. History of recent myocardial infarction
  11. History of interstitial lung disease, pulmonary fibrosis or symptomatic pulmonary disease
  Contacts and Locations
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Please refer to this study by its identifier: NCT01331824

United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Matthew Galsky
Celgene Corporation
Principal Investigator: Matthew D Galsky, MD Icahn School of Medicine at Mount Sinai
  More Information

Responsible Party: Matthew Galsky, MD, Icahn School of Medicine at Mount Sinai Identifier: NCT01331824     History of Changes
Other Study ID Numbers: GCO 10-1341
Study First Received: April 6, 2011
Results First Received: October 15, 2015
Last Updated: November 21, 2015

Keywords provided by Icahn School of Medicine at Mount Sinai:
Bladder Cancer
Urothelial Cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents processed this record on April 28, 2017