A Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (CRPC)

NCT01090765 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 10006210-C-0062
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Currently, there is no curative therapy for metastatic castrate-resistant prostate cancer (CRPC), a leading cause of death in men. However, researchers are exploring new treatments that involve drugs that prevent angiogenesis (the process by which new blood vessels are formed) and can slow or prevent tumor growth.
• TRC105 is an experimental drug that blocks angiogenesis, and has been studied for possible use in treating different kinds of cancer. However, it has not been validated to treat prostate cancer in general or CRPC in particular. Objectives:
• To determine the effects of TRC105 as a treatment for CRPC
• To determine the safety and effectiveness of TRC105 in treating CRPC Eligibility: \- Men at least 18 years of age who have been diagnosed with castrate-resistant prostate cancer for which existing treatments have not been effective. Design:
• Eligible individuals will have a series of blood and other tests to determine their suitability for participating in the study.
• Participants will receive intravenous infusions of TRC105 in a 28-day treatment cycle. Participants will receive i.v. (intravenous) infusions of TRC105 every two weeks on days 1 and 15 of each 28-day cycle (cohorts 1, 2, 3, 5, and 6) and every week on days 1, 8, 15, and 22 of each 28 day cycle (cohort 4).
• Participants will receive different doses of TRC105 depending on when they enter the study, up to a maximum tolerated dose or optimum treatment dose.
• Frequent blood and urine tests will be performed during treatment, as well as other tests of cancer progression as directed by the study doctors. Participants will receive medicines to help prevent possible adverse side effects of TRC105, such as allergic reaction to the drug.
• Participants will continue treatment with TRC105 until they or the study team decides that the medication is not beneficial. No additional testing will be required unless participants discontinue the treatment because of side effects (which the study doctors will follow until the side effects are resolved).

Conditions

Prostate Cancer; Metastatic Castrate Resistant Prostate Cancer

Keywords

Prostate; Tumor; Cancer; Hormone; Androgen; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Phase I: Maximum Tolerated Dose (MTD) of TRC105 Given Every Two Weeks.

  The MTD, to be administered in the phase II portion, is defined as the highest dose studied for which the incidence of dose limiting toxicity (DLT) was less than 33%. TRC105 was administered at 20 mg/kg intravenous every two weeks until MTD was achieved.

  6 months

Secondary Outcomes (4)

• Number of Participants With Adverse Events

  Date treatment consent signed to date off study, approximately 43 months, 5 days

• Dose Limiting Toxicity (DLT)

  First 28 days on study

• Prostatic-Specific Antigen (PSA) Decline

  1- week intervals up to 6 months

• Clinical Response

  56 days (one cycle = 28 days, restaging post cycle 2)

Study Arms (6)

TRC105 1 mg/kg every 2 weeks

EXPERIMENTAL

Intravenous infusion at 1 mg/kg every 2 weeks

Drug: TRC105

TRC105 3 mg/kg every 2 weeks

EXPERIMENTAL

Intravenous infusion at 3 mg/kg every 2 weeks

Drug: TRC105

TRC105 10 mg/kg every 2 weeks

EXPERIMENTAL

Intravenous infusion at 10 mg/kg every 2 weeks

Drug: TRC105

TRC105 10 mg/kg weekly

EXPERIMENTAL

Intravenous infusion at 10 mg/kg weekly

Drug: TRC105

TRC105 15 mg/kg every 2 weeks

EXPERIMENTAL

Intravenous infusion at 15 mg/kg every 2 weeks

Drug: TRC105

TRC105 20 mg/kg every 2 weeks

EXPERIMENTAL

Intravenous infusion at 20 mg/kg every 2 weeks

Drug: TRC105

Interventions

TRC105 DRUG

TRC105 1 mg/kg every 2 weeks; TRC105 10 mg/kg every 2 weeks; TRC105 10 mg/kg weekly; TRC105 15 mg/kg every 2 weeks; TRC105 20 mg/kg every 2 weeks; TRC105 3 mg/kg every 2 weeks

Eligibility Criteria

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

You may qualify if:

• Patients must have histopathological confirmation of prostate cancer by the Laboratory of Pathology of the National Cancer Institute (NCI), Pathology Department of the National Naval Medical Center or Pathology Department of Walter Reed Army Medical Center prior to entering this study. Patients whose pathology specimens are no longer available may be enrolled in the trial if the patient has a clinical course consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis. In cases where original tissue blocks or archival biopsy material is available, efforts will be made to contact referring physicians and outside pathology departments to have the material forwarded to the research team for use in correlative studies.
• Patients must have metastatic progressive castrate-resistant prostate cancer defined as progressive disease (see below) despite surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone.
• Criteria of progression for trial eligibility are defined from the Prostate Cancer Clinical Trials Working Group-2. Clinically progressive prostate cancer must be evidenced and documented by any of the following parameters:
• Two consecutively rising prostate specific antigen (PSA) values at a minimum of 1-week intervals (2.0 ng/mL is the minimum starting value for PSA)
• Appearance of one or more new lesion on bone scans
• Progressive measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients on flutamide for at least 6 months must have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide for at least 6 months must have progression at least 6 weeks after withdrawal.
• All patients enrolled will be required to have measurable or non-measurable disease on imaging studies.
• \. Age greater than or equal to 18 years.
• \. Life expectancy of greater than 3 months.
• \. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• \. Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count greater than or equal to 1,500/mcL
• Platelets greater than or equal to 100,000/mcL
• Total bilirubin less than or equal to 1.5 times upper normal limits or less than 3 mg/dl in subjects with Gilbert's Syndrome

You may not qualify if:

• Patients who have had chemotherapy, large field radiotherapy, or major surgery must wait 3 weeks prior to entering the study.
• Patients may not be receiving any agents not approved by the Food and Drug Administration (FDA) within the past 4 weeks.
• Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Proteinuria, as demonstrated by a 24 hour protein of (Bullet) 2000 mg. Urine protein will be screened by urine protein-creatinine ratio (UPC). For UPC ratio \> 1.0, a 24-hour urine protein will need to be obtained and the level should be \< 2000 mg for patient enrollment.
• Uncontrolled intercurrent illness including, but not limited to, hypertension (systolic blood pressure (BP) \> 160, diastolic BP \> 100), ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
• Thrombolytic or treatment-dose anticoagulant use within 10 days prior to first dose with TRC105.
• Hemorrhage within 30 days of dosing.
• History of peptic ulcer disease or gastritis within 6 months of TRC105 administration, unless patient has received adequate treatment for peptic ulcer disease and has evidence of complete resolution documented by esophagogastroduodenoscopy (EGD).
• Corrected QT interval (QTc) \> 500 msec.
• Known human immunodeficiency virus (HIV)-positive patients are excluded.
• History of hypersensitivity reaction to human or mouse antibody products.
• Patients with a history of familial bleeding disorders.
• Patients with a history of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).
• Use of non-steroidal anti-inflammatory drugs (NSAIDs) beginning 14 days prior to the first TRC105 dose, with the exception of aspirin when clinically indicated.

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 (3)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Grossfeld GD, Stier DM, Flanders SC, Henning JM, Schonfeld W, Warolin K, Carroll PR. Use of second treatment following definitive local therapy for prostate cancer: data from the caPSURE database. J Urol. 1998 Oct;160(4):1398-404.

  PMID: 9751363 BACKGROUND

• Figg WD, Feuer JA, Bauer KS. Management of hormone-sensitive metastatic prostate cancer. Update on hormonal therapy. Cancer Pract. 1997 Jul-Aug;5(4):258-63. No abstract available.

  PMID: 9250085 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

carotuximab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. William Dahut
• Organization: National Cancer Institute

dahutw@mail.nih.gov

301-496-4251

Study Officials

• William L Dahut, 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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 19, 2010
• First Posted: March 22, 2010
• Study Start: February 23, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 17, 2015
• Last Updated: May 22, 2018
• Results First Posted: February 13, 2015

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)