Study of TRC105 With Abiraterone and With Enzalutamide in Prostate Cancer Patients Progressing on Therapy

NCT03418324 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IIT2016-16-POSADAS-TRC105
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is being done to measure the clinical benefit of TRC105 in combination with abiraterone or enzalutamide in metastatic, castration-resistant prostate cancer patients who are taking either abiraterone or enzalutamide and showing signs of biochemical progression without radiographic progression. A patient who is progressing on AR-therapy will continue the same AR-therapy on study with the addition of TRC105. The two arms will accrue in parallel and independently.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Metastatic Prostate Cancer; Castration Resistant Prostate Cancer; Metastatic Castration Resistant

Outcome Measures

Primary Outcomes (1)

• Overall Clinical Benefit

  Number of participants with stabilization of disease for at least 2 months or disease improvement at any time from start of combination therapy by radiographic and/or biochemical criteria through treatment completion up to an estimated period of 24 months * radiographic improvement defined as a PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum. There can be no appearance of new lesions) or CR (Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions) by RECIST 1.1 or improvement by PCWG3 criteria * Biochemical response will be defined by PCWG3 criteria * Stabilization will be defined as the absence of progression by BOTH radiographic and biochemical criteria

  Through study completion, average 24 months

Secondary Outcomes (6)

• Adverse Events From TRC105 and Abiraterone or Enzalutamide

  4 months

• Progression Free Survival

  24 months

• Clinical Benefit at Two Months

  2 months

• Clinical Benefit at Four Months

  4 months

• Clinical Benefit From PSA Serum Concentration (2 Months)

  2 months

Study Arms (2)

Arm A: TRC105 + Abiraterone

EXPERIMENTAL

Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone

Drug: TRC105; Drug: Abiraterone

Arm E: TRC105 + Enzalutamide

EXPERIMENTAL

Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide

Drug: TRC105; Drug: Enzalutamide

Interventions

TRC105 DRUG

Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks

Also known as: Carotuximab

Arm A: TRC105 + Abiraterone; Arm E: TRC105 + Enzalutamide

Abiraterone DRUG

Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.

Also known as: Zytiga

Arm A: TRC105 + Abiraterone

Enzalutamide DRUG

Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.

Also known as: Xtandi

Arm E: TRC105 + Enzalutamide

Eligibility Criteria

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

You may qualify if:

• History of metastatic, castration-resistant prostate cancer with rising PSA on either abiraterone or enzalutamide
• PSA rise will be defined as an increase in PSA of 0.2 ng/mL or higher on at least 2 separate occasions greater than 1 week apart while on either abiraterone or enzalutamide
• If there is a drop in serum PSA after the first rise, and the patient has another PSA rise which is greater than the first, the patient will still be considered eligible.
• ECOG 0-2
• Resolution of adverse events results as described below.
• Laboratory abnormalities must meet values specified below in criteria #4
• If the patient's most recent line of therapy is treatment with abiraterone or enzalutamide, then all adverse events must be resolved to Grade 2 or better
• If the most recent line of therapy is any other treatment for mCRPC then all Adverse events must be resolved to grade 1 or better, with the exception of fatigue, alopecia and neuropathy (which must resolve to CTCAE grade 2)
• Adequate organ function defined by:
• AST and ALT \< 2.5 x ULN
• Total serum bilirubin \< 1.5 x ULN
• Platelets \> 60,000
• Hgb \> 8.5 g/dL
• Serum Cr \<1.5 x ULN or a creatinine clearance \> 30.
• INR ≤ 1.2 unless the patient is receiving a direct Factor Xa inhibitor or a direct thrombin inhibitor

You may not qualify if:

• Non-PSA producing prostate cancers- such as small cell prostate cancers or those prostate cancers which exhibit radiographic progression without PSA rise
• Inability to tolerate standard doses of abiraterone (1000 mg daily) or enzalutamide (160 mg daily).
• Other prior malignancy requiring active anticancer therapy
• Prior exposure to TRC105 or any CD105 targeted antibody
• Any major surgical procedure within 2 weeks of starting therapy
• Uncontrolled chronic hypertension defined as sustained by systolic pressure (SBP) \>150 mmHg or diastolic pressure (DBP) \>90 despite optimal therapy.
• Active bleeding or pathologic conditions that carries a high bleeding risk
• Use of thrombolytics within 10 days prior to the first day of TRC105
• Known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies
• A known diagnosis of Osler-Weber-Rendu syndrome
• Ascites or pericardial or pleural effusion requiring external drainage procedures
• History of untreated brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 28 days. Imaging for CNS disease will not be required for screening unless there is a history of a neurological finding such as new onset weakness or numbness that cannot be explained by other medical history.
• Acute cardiovascular event within the past 6 months. An acute cardiovascular event will be defined as a myocardial infraction, NYHA Class II or worse congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or CABG. Deep venous thrombosis within 6 months, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

carotuximab; abiraterone; Abiraterone Acetate; enzalutamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Early accrual closure due to manufacturer's limited drug supply.

Results Point of Contact

• Title: Edwin Posadas, MD
• Organization: Cedars-Sinai Medical Center

Edwin.Posadas@cshs.org

310-423-7600

Study Officials

• Edwin Posadas, MD FACP

  Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Urologic Oncology Program

Model Details: Bayesian design

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: February 1, 2018
• Study Start: March 5, 2018
• Primary Completion: November 6, 2019
• Study Completion: November 6, 2019
• Last Updated: December 30, 2020
• Results First Posted: December 30, 2020

Record last verified: 2020-12

Locations

US (1)