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Prostate CancerPhase 2NCT03418324

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

A Phase 2 study testing TRC105, Abiraterone and Enzalutamide in people with Prostate Cancer, run by Cedars-Sinai Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
TRC105, Abiraterone and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
5 Mar 2018to 6 Nov 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • 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. Abstinence from intercourse is an acceptable form of contraception.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

Other trials in United States

About this study

Official title: A Phase 2 Study of TRC105 (Anti-endoglin Antibody) With Abiraterone and With Enzalutamide in Metastatic, Castration Resistant Prostate Cancer Patients Progressing on Therapy

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.

Read the detailed description

This is a Phase II, open-label study of TRC105 (anti-endoglin antibody) 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.

There will be a 2-week washout of the active AR-targeted therapy prior to initiation of combination therapy. Tumor response should be assessed at a frequency of 8 weeks by CT/MRI chest, abdomen and pelvis as well as bone scan. Patients may continue on therapy until radiographic progression by RECIST 1.1 or PCWG3 criteria.

Conditions
Prostate Cancer
Being tested
TRC105, Abiraterone, Enzalutamide
Keywords
Prostate Cancer, Metastatic Prostate Cancer, Castration Resistant Prostate Cancer, Metastatic Castration Resistant
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TRC105Drug

    Also called Carotuximab

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

  • AbirateroneDrug

    Also called Zytiga

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

  • EnzalutamideDrug

    Also called Xtandi

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

Study groups in NCT03418324
Study groupRoleWhat they receive
Arm A: TRC105 + AbirateroneExperimentalPatients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone
Receives: Drug: TRC105; Drug: Abiraterone
Arm E: TRC105 + EnzalutamideExperimentalPatients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide
Receives: Drug: TRC105; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Through study completion, average 24 months

Secondary outcomes (6)

  1. Adverse Events From TRC105 and Abiraterone or Enzalutamide

    Number of participants with grade 3/4 Adverse Events Related to investigational therapy as assessed Using CTCAE (v.4) up to 4 months from treatment initiation.

    Measured: 4 months

  2. Progression Free Survival

    Time (in Months) from treatment initiation to radiographic and clinical progression over study duration (estimated 24 months)

    • radiographic criteria measured by RECIST 1.1 [Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions plus an absolute increase of at least 5 mm, taking as reference the smallest sum recorded since the start of study]

    Measured: 24 months

  3. Clinical Benefit at Two Months

    Proportion of participants with stabilization of disease for two months or disease improvement at anytime from start of combination therapy to two months by radiographic and/or biochemical criteria

    • 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

    Measured: 2 months

  4. Clinical Benefit at Four Months

    Proportion of participants with stabilization of disease for at least 4 months or disease improvement at anytime from start of combination therapy to four months by radiographic and/or biochemical criteria

    • 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

    Measured: 4 months

  5. Clinical Benefit From PSA Serum Concentration (2 Months)

    Proportion of participants with stabilization of disease based on PSA serum concentration levels. Stabilization of disease refers to PSA values that do not meet criteria for progression where progression will be defined as a rise in serum PSA that is ≥ 25% and 2 ng/mL above nadir which is confirmed by a second value ≥ 3 weeks later.

    Measured: 2 months

  6. Clinical Benefit From PSA Serum Concentration (4 Months)

    Proportion of participants with stabilization of disease based on PSA serum concentration levels. Stabilization of disease refers to PSA values that do not meet criteria for progression where progression will be defined as a rise in serum PSA that is ≥ 25% and 2 ng/mL above nadir which is confirmed by a second value ≥ 3 weeks later.

    Measured: 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2018
  2. Study start5 Mar 2018
  3. Primary completion6 Nov 2019
  4. Study completion6 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Bayesian design
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03418324
Sponsor's protocol ID
IIT2016-16-POSADAS-TRC105
Status last verified
Dec 2020
First submitted
23 Jan 2018
Last updated
30 Dec 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TRC105, Abiraterone and Enzalutamide in people with Prostate Cancer, run by Cedars-Sinai Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Clinical Benefit (time frame: Through study completion, average 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03418324.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2020.

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