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

NCT01331824 | Terminated Phase 2 Results DMC

• 1 other identifier: GCO 10-1341
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Bladder Cancer; Urothelial Cancer; Chemotherapy; Second-line; Metastatic

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  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.

  6 weeks

Secondary Outcomes (3)

• Progression-free Survival

  Every 3 months post Amrubicin administration

• Overall Survival

  1 year

• Safety as Measured by the Frequency and Type of Adverse Events as Per the Common Terminology for Adverse Events (CTCAE) Version 4.0.

  Day 1 of each treatment cycle; and 21 days after the last dose of amrubicin

Study Arms (1)

Amrubicin

EXPERIMENTAL

35 mg/m2/day intravenously

Drug: Amrubicin

Interventions

Amrubicin DRUG

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

Amrubicin

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Age \> 18 years
• Karnofsky performance status of ≥ 80%
• Histological or cytological proof of transitional cell carcinoma of the urothelial tract. The primary site may include: urethra, bladder, ureters, and renal pelvis.
• 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.
• Measurable disease according to RECIST 1.1
• 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.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
• 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);

You may not qualify if:

• Has had major surgery within 30 days of starting study treatment.
• Has active CNS metastases. Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
• 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.
• Has had treatment with another anticancer agent or investigational agent within 30 days prior to being registered for protocol therapy.
• 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.
• Has a clinically significant infection as judged by the treating investigator.
• Pregnant or nursing females.
• 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.
• History of congestive heart failure
• History of recent myocardial infarction
• History of interstitial lung disease, pulmonary fibrosis or symptomatic pulmonary disease

Sponsors & Collaborators

• Matthew Galsky: lead
• Celgene: collaborator

Study Sites (3)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplasm Metastasis

Interventions

amrubicin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The trial was terminated prematurely due to the results of a phase 3 study seeking registration for amrubicin in small cell lung cancer in the United States, leading the industry funder to discontinue further clinical development of amrubicin.

Results Point of Contact

• Title: Dr. Matthew D. Galsky
• Organization: Icahn School of Medicine at Mount Sinai

matthew.galsky@mssm.edu

212-241-6756

Study Officials

• Matthew D Galsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 6, 2011
• First Posted: April 8, 2011
• Study Start: February 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2015
• Last Updated: April 23, 2018
• Results First Posted: December 24, 2015

Record last verified: 2018-03

Locations

US (3)