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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: TRC105 + Abiraterone | Experimental | Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone |
|
| Arm E: TRC105 + Enzalutamide | Experimental | Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TRC105 | Drug | Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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
| Through study completion, average 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 months |
| Progression Free Survival |
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Inclusion Criteria:
History of metastatic, castration-resistant prostate cancer with rising PSA on either abiraterone or enzalutamide
ECOG 0-2
Resolution of adverse events results as described below.
Adequate organ function defined by:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Edwin Posadas, MD FACP | Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars Sinai Medical Center | Los Angeles | California | 90048 | United States |
Early accrual closure due to manufacturer's limited drug supply.
Study opened to accrual February 5, 2018 and the first patient on study March 5, 2018. As of November 6, 2019, 12 patients have been consented, 11 were enrolled, and 11 were off-treatment and off-study. Study closed to accrual on May 1, 2019, as drug manufacturer has limited drug supply without plans to increase production.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: TRC105 + Abiraterone | Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105. |
| FG001 | Arm E: TRC105 + Enzalutamide | Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: TRC105 + Abiraterone | Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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
| Posted | Count of Participants | Participants | Through study completion, average 24 months |
|
2 years
3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: TRC105 + Abiraterone | Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary retention | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic reaction | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
Early accrual closure due to manufacturer's limited drug supply.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Edwin Posadas, MD | Cedars-Sinai Medical Center | 310-423-7600 | Edwin.Posadas@cshs.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 24, 2017 | Jan 23, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C579557 | carotuximab |
| C089740 | abiraterone |
| D000069501 | Abiraterone Acetate |
| C540278 | enzalutamide |
| ID | Term |
|---|---|
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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Bayesian design
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| Abiraterone | Drug | Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105. |
|
|
| Enzalutamide | Drug | Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105. |
|
|
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] |
| 24 months |
| 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
| 2 months |
| 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
| 4 months |
| 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. | 2 months |
| 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. | 4 months |
| BG001 | Arm E: TRC105 + Enzalutamide | Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone
TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks
Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.
| OG001 | Arm E: TRC105 + Enzalutamide | Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105. |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 4 months |
|
|
|
| Secondary | 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] | Median progression free survival (months) (95% confidence interval). Not enough data (insufficient number of participants with events) to establish upper limit. | Posted | Median | 95% Confidence Interval | months | 24 months |
|
|
|
| Secondary | 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
| Posted | Count of Participants | Participants | 2 months |
|
|
|
|
| Secondary | 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
| Posted | Count of Participants | Participants | 4 months |
|
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 2 months |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 4 months |
|
|
|
| 0 |
| 3 |
| 1 |
| 2 |
| 2 |
| 2 |
| EG001 | Arm E: TRC105 + Enzalutamide | Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105. | 1 | 8 | 0 | 6 | 6 | 6 |
| Cellulitis (peri-mandibular) | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anemia Hemoglobin (Hgb) | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysphasia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Generalized weakness | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Guaiac + Stool | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Petechiae | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Cauda equina | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cellulitis (peri-mandibular) | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Right leg sciatica | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Bruising | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Cataract | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Geographic Tongue | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Glaucoma | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Infusion related reaction | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Laryngitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Lip pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Localized edema | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| MRSA | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Recurrent laryngeal nerve palsy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Redness sclera left eye | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rhinitis infective | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Vision decrease (binocular) | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D011083 |
| Polycyclic Compounds |
| Biochemical Response |
|
| Stabilization |
|
| Binomial proportion |
| 66.7 |
| 2-Sided |
| 95 |
| 22.3 |
| 95.7 |
| Other |
Binomial proportion (Clopper-Pearson exact confidence interval) for each arm. |
| Biochemical Response |
|
| Stabilization |
|
| Binomial proportion |
| 50 |
| 2-Sided |
| 95 |
| 11.8 |
| 88.2 |
| Other |
Binomial proportion (Clopper-Pearson exact confidence interval) for each arm. |