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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Mount Sinai School of Medicine
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Matthew Galsky, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01331824
First received: April 6, 2011
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

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: Endpoint Classification: Safety/Efficacy Study
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 Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Objective Response Rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Tumor measurements via CT chest, abdomen, and pelvis for restaging after every 2 cycles


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Every 3 months post Amrubicin administration ] [ Designated as safety issue: No ]
    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.

  • Survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 35
Study Start Date: February 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01331824

Contacts
Contact: Matthew D. Galsky, MD 212-659-5426 matthew.galsky@mssm.edu

Locations
United States, Arizona
Banner MD Anderson Cancer Center Not yet recruiting
Gilbert, Arizona, United States, 85234
Contact: Bryan Wong, MD, PhD    480-256-3657      
Principal Investigator: Bryan Wong, MD, PhD         
United States, Indiana
Indiana University Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Marietta Moore    317-274-7477      
Principal Investigator: Noah Hahn, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Matthew D. Galsky, MD    212-659-5426    matthew.galsky@mssm.edu   
Principal Investigator: Matthew D Galsky, MD         
Sub-Investigator: William Oh, MD         
Sponsors and Collaborators
Matthew Galsky
Celgene Corporation
Investigators
Principal Investigator: Matthew D Galsky, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Matthew Galsky, MD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01331824     History of Changes
Other Study ID Numbers: GCO 10-1341
Study First Received: April 6, 2011
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Bladder Cancer
Urothelial Cancer
Chemotherapy
Second-line
Metastatic

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Amrubicin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014