TRC105 in Adults With Advanced/Metastatic Urothelial Carcinoma

NCT01328574 | Completed Phase 2 Results

• 2 other identifiers: 11013011-C-0130
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Urothelial cancer (tumors of the bladder, urethra, ureter, or renal pelvis) often responds initially to standard chemotherapy treatments, but frequently recurs and can often spread to other parts of the body. TRC105, an experimental drug that blocks the development of the new blood vessels needed for tumor growth, may be able to shrink or stabilize urothelial cancer tumors. TRC105 has been given previously to individuals with other types of cancer, and researchers are interested in determining its safety and effectiveness in treating urothelial cancer. Objectives: \- To determine the safety and effectiveness of TRC105 as a treatment for metastatic urothelial cancer that has not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with urothelial cancer that has spread to other parts of the body and has not responded to standard chemotherapy. Design:

• Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies.
• Participants will receive TRC105 intravenously once every 2 weeks on days 1 and 15 of a 28-day treatment cycle. The first dose of TRC105 will be given over a 4-hour period; participants who do not have side effects may receive the next dose over 2 hours. If the second dose is tolerated, subsequent doses can be given over at least 1 hour.
• To help prevent known side effects of TRC105, participants will take two doses (one in the morning and one in the evening) of the steroid dexamethasone on the day before each infusion is scheduled. Participants may have additional dexamethasone 30 minutes before infusion, and may have the infusion slowed or stopped to adjust for side effects.
• Participants will be monitored with blood samples, physical examinations, and tumor imaging studies through the cycles of treatment.
• Participants will continue to take TRC105 for as long as the treatment is effective against the cancer and as long as the side effects are not severe enough to stop treatment.

Conditions

Urothelial Carcinoma; Ureteral Neoplasms; Ureter Cancer; Neoplasm, Ureteral; Cancer of the Ureter

Keywords

Progression-Free Survival; Carcinoma of the Bladder; Cancer of the Renal Pelvis; Ureter Cancer; Survival; Bladder Cancer; Renal Pelvis Cancer; Urothelial Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Time interval from start of treatment to documented evidence of disease progression. Progressive disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression).-

  after 6 months on study

Secondary Outcomes (4)

• Number of Participants With Adverse Events

  24 months

• Objective Response

  up to 25 months

• Median Overall Survival

  up to 25 months

• Incidence of TRC-105-Related Adverse Events

  24 months

Study Arms (1)

Single Arm - TRC105 in Urothelial Carcinoma

EXPERIMENTAL

TRC105 15 mg/kg/dose every two weeks

Drug: TRC105

Interventions

TRC105 DRUG

15 mg/kg intravenously

Single Arm - TRC105 in Urothelial Carcinoma

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis, with histological confirmation at the Laboratory of Pathology of the NCI (National Cancer Institute), NIH (National Institutes of Health).
• Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging. Patients must have at least:
• One measurable site of disease (according to RECIST criteria) that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Or, appearance of one new bone lesion.
• Patients must have been previously treated, as defined by the following:
• Treatment with at least one prior cytotoxic agent (which must have included at least one of the following: cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine), administered in the perioperative or metastatic setting and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or as part of a single regimen.
• years of age or older
• ECOG (Eastern Cooperative Oncology Group) performance status of \< 2 or Karnofsky Performance Status greater than or equal to 60%
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedure to NCI CTCAE (Common Terminology Criteria in Adverse Events) grade less than or equal to 1 or baseline
• Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST (Aspartate transaminase); serum glutamic oxaloacetic transaminase \[SGOT (serum glutamic oxaloacetic)\]) and serum alanine transaminase (ALT (alanine transaminase); serum glutamic pyruvic transaminase \[SGPT (serum glutamic pyruvic transaminase)\]) less than or equal to 2.5 times the upper limit of normal (ULN); 5.0 times the ULN in cases of liver metastases
• Total serum bilirubin less than or equal to 1.5 mg/dL (unless elevation from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin)
• Absolute neutrophil count (ANC) greater than or equal to 1000/microL
• Platelets greater than or equal to 100,000/microL
• Serum creatinine less than or equal to 2.0 mg/dl or calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min

You may not qualify if:

• Receipt of an investigational agent within 4 weeks prior to first dose with TRC105
• Major surgery including open biopsy or systemic therapy \< 4 weeks prior to first dose with TRC105
• Radiation therapy (except small field) \< 3 weeks prior to first dose with TRC105
• Small field radiation therapy \< 2 weeks prior to first dose with TRC105
• Minor surgical procedures within 2 weeks
• Uncontrolled chronic hypertension (systolic \> 140 or diastolic \> 90mm Hg despite optimal therapy)
• Brain metastasis, or leptomeningeal disease because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Unstable angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT (deep vein thrombosis), PTCA (percutaneous transluminal coronary angioplasty) or CABG (coronary artery bypass graft) within the past 6 months
• Cardiac arrhythmias of NCI CTCAE grade greater than or equal to 2 within the last month
• Serious, non-healing wound, ulcer, or bone fracture
• Known active hepatitis
• Hemorrhage within 30 days of dosing or history of persistent gross hematuria
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
• History of hypersensitivity reaction to human or mouse antibody products
• Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.: hysterectomy) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. All female patients of reproductive potential must have a negative pregnancy test (serum) within 7 days prior to first dose. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Apolo AB, Karzai FH, Trepel JB, Alarcon S, Lee S, Lee MJ, Tomita Y, Cao L, Yu Y, Merino MJ, Madan RA, Parnes HL, Steinberg SM, Rodriguez BW, Seon BK, Gulley JL, Arlen PM, Dawson NA, Figg WD, Dahut WL. A Phase II Clinical Trial of TRC105 (Anti-Endoglin Antibody) in Adults With Advanced/Metastatic Urothelial Carcinoma. Clin Genitourin Cancer. 2017 Feb;15(1):77-85. doi: 10.1016/j.clgc.2016.05.010. Epub 2016 May 27.

  PMID: 27328856 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Ureteral Neoplasms; Urinary Bladder Neoplasms

Interventions

carotuximab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ureteral Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases

Results Point of Contact

• Title: Dr. Andrea Apolo
• Organization: National Cancer Institute

apoloab@mail.nih.gov

301-451-1984

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 1, 2011
• First Posted: April 4, 2011
• Study Start: March 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 13, 2017
• Results First Posted: March 2, 2015

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)