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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Prostate Cancer, Metastatic Castrate Resistant Prostate Cancer

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Trial Information

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


- Inhibition of angiogenesis has demonstrable antitumor efficacy against castrate-resistant
prostate cancer (CRPC). TRC105 is a human/murine chimeric IgG1 kappa monoclonal antibody
that binds to human CD105 (endoglin), thus inhibiting angiogenesis and tumor growth. Data
from an ongoing phase I clinical trial suggest that TRC105 is well tolerated with evidence
of clinical efficacy in patients with metastatic CRPC.

Primary Objectives:

- Define the maximum tolerable dose (MTD) of TRC105 given every one to two weeks.

- Determine if single-agent TRC105, when administered at 20 mg/kg IV every two weeks (the
phase I MTD) to patients with CRPC, is associated with a 6-month progression-free
survival probability of 30%

Secondary Objectives:

- Define the dose-limiting toxicities and toxicity profile of TRC105 given every one to
two weeks

- Evaluate time to disease progression, overall response rate and overall survival.

- Describe the prostate specific antigen (PSA) response rate to therapy with TRC105

- Characterize the pharmacokinetics of TRC105

- Demonstrate a biologic effect of TRC105 in the patient and, when possible, on the tumor
via laboratory evaluation of the molecular markers of angiogenesis before and after
drug administration respectively


- Progressive, castrate-resistant, metastatic adenocarcinoma of the prostate

- ECOG less than or equal to 2


- An initial single-arm, phase I dose escalation study open to all patients with
progressive metastatic CRPC. The study will evaluate patients in five cohorts of
escalating dose levels. A maximum of 30 patients will be needed to complete the phase I

- Following completion of the phase I study will be a two-stage, phase II study that will
be conducted separately in the following two arms:

1. Chemotherapy-na ve for metastatic disease (no prior antiangiogenic therapy)

2. Post-docetaxel disease progression

- In each arm, the primary objective will be to determine if a 6 month progression free
survival probability of 30.0% can be identified.

- Initially, 12 patients will be enrolled in each stratum and evaluated for progression.
If 2 or more are progression-free at 6 months, then enrollment will continue until a
full 35 patients have been enrolled in that stratum. Enrollment may continue to the
other stratum if one stratum has ended accrual.

Inclusion Criteria


1. Patients must have histopathological confirmation of prostate cancer by the
Laboratory of Pathology of the 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.

2. 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

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:

1. Two consecutively rising PSA values at a minimum of 1-week intervals (2.0 ng/mL
is the minimum starting value for PSA)

2. Appearance of one or more new lesion on bone scans

3. Progressive measurable disease by 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.

3. Phase II study patients enrolled onto Arm 1 (chemotherapy-na ve) may not have
received any prior chemotherapy or antiangiogenic therapy for metastatic prostate
cancer. Those patients enrolled onto Arm 2 must have evidence of disease progression
(per criteria stated above) despite prior docetaxel. Any number of prior treatment
lines is acceptable.

4. Age greater than or equal to 18 years.

5. Life expectancy of greater than 3 months.

6. ECOG performance status 0-2.

7. 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

- AST/ALT less than or equal to 2.5 times upper limit of normal

- Creatinine less than or equal to 1.5 times upper normal limits OR creatinine
clearance greater than or equal to 40 mL/min/1.73 m(2) for patients with
creatinine levels above institutional normal, as calculated by the Cockcroft
Gault formula.

8. Patients must have recovered from any acute toxicity related to prior therapy,
including surgery. Toxicity should be less than or equal to grade 1 or returned to

9. All patients who have not undergone bilateral surgical castration must continue
suppression of testosterone production by appropriate usage of GnRH agonists or

10. Patients must not have other invasive malignancies (within the past 2 years with the
exception of non-melanoma skin cancers or non-invasive bladder cancer).

11. Enrolled patients must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry, the duration of study
participation and 3 months after the end of the treatment.

12. Patient must be able to understand and willing to sign a written informed consent

13. Patients on a stable dose of steroids of 10 mg/day or less can continue on steroids
if they are on peptic ulcer disease prophylaxis with an H2-blocker or proton pump


1. Patients who have had chemotherapy, large field radiotherapy, or major surgery must
wait 3 weeks prior to entering the study.

2. Patients may not be receiving any agents not approved by the FDA within the past 4

3. 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

4. Proteinuria, as demonstrated by a 24 hour protein of >= 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

5. Uncontrolled intercurrent illness including, but not limited to, hypertension
(systolic 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

6. Thrombolytic or treatment-dose anticoagulant use within 10 days prior to first dose
with TRC105.

7. Hemorrhage within 30 days of dosing.

8. 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 EGD.

9. QTc > 500 msec.

10. Known HIV-positive patients are excluded.

11. History of hypersensitivity reaction to human or mouse antibody products.

12. Patients with a history of familial bleeding disorders.

13. Patients with a history of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu

14. 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Define the maximum tolerable dose (MTD) of TRC105 given every two weeks. Determine if single-agent TRC105, when administered at MTD to patients with CRPC, is associated with a 6-month progression-free survival probability of 30%.

Outcome Time Frame:

6 month progression - free survival

Safety Issue:


Principal Investigator

William L Dahut, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

February 2010

Completion Date:

March 2014

Related Keywords:

  • Prostate Cancer
  • Metastatic Castrate Resistant Prostate Cancer
  • Prostate
  • Tumor
  • Cancer
  • Hormone
  • Androgen
  • Prostate Cancer
  • Prostatic Neoplasms



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892