Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Trophoblastic Neoplasms

Choriocarcinoma

Trophoblastic Tumor, Placental Site

Gestational Trophoblastic Disease

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Pregnancy Complications

Pregnancy Complications, Neoplastic

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Gestational Trophoblastic Tumor

Antineoplastic Agents

All Drugs and Chemicals

Vasodilator Agents

Bevacizumab

Antibodies

Nitroglycerin

Angiogenesis Inhibitors

Immunoglobulins

Antineoplastic Agents, Immunological

Growth Inhibitors

All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks.

Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing.

TRC105

Bevacizumab will be dosed every two weeks.

Charles Theuer, MD, PhD

The purpose of the study is to determine the overall response rate of single agent TRC105 and the combination of TRC105 and bevacizumab in patients with refractory GTN (including choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)). Up to 30 patients will be treated.

TRC105 is a monoclonal antibody that binds to endoglin, an angiogenic target highly expressed on the tumor vessels and tumor cells in gestational trophoblastic neoplasia (GTN). Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105 has been well tolerated as a single agent and when combined with bevacizumab. These antibodies may be efficacious in refractory GTN, a tumor type that is highly vascular and has been shown to densely express endoglin.

Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)

A Phase 2A Study of TRC105 (With Option to Add Bevacizumab) in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)

Antitumor Activity of Single Agent TRC105 and the Combination of TRC105 and Bevacizumab will be assessed via RECIST 1.1 and by measuring circulating bHCG. Disease progression is defined as \>20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.

Median Progression-Free Survival (PFS) via Serum hCG levels and response evaluation according to RECIST version 1.1 as a preliminary measure of the antitumor activity of TRC105. Disease progression is defined as \>20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks. Patients must have screening (baseline) and at least one on study CT scan to be considered evaluable.

Overall Response Rate on bevacizumab alone according to RECIST 1.1 in combination with serum hCG levels. Disease progression is defined as \>20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.

Mean serum TRC105 concentrations were assessed at cycle 1 and cycle 2 on day 1, 8, 15, and 22 and on day 1 of every subsequent cycle using validated methods in order to determine the Cmax of TRC105

Anti-Product Antibody (APA) concentrations will be measured using validated ELISA methods at the time points specified in the protocol. APA concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles. Number of patients with positive APA titers on study will be reported.

Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.03)

Tracon Pharmaceuticals Inc.

All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks.

TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing.

Bevacizumab: Bevacizumab will be dosed every two weeks.

TRC105 and/or Bevacizumab

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Number of Prior Regimens

Medical Monitor

Number of patients with best response of PR

Number of patients with best response of SD

Number of patients with best response of PD

Number of patients with best response of CR

All patients who had a baseline scan and at least 1 on study assessment

Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab

Progression-Free Survival (PFS)

Overall Response Rate on Bevacizumab Alone

Maximum Plasma Concentration (Cmax) of TRC105.

TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).

Participants who experienced an SAE

Participants who experienced a TRC105 related SAE

Frequency and Severity of Adverse Events

Overall Study

Escalating doses of i.v. TRC105 will be administered weekly beginning with 3 mg/kg in combination with 15 mg/kg bevacizumab given every 3 weeks. Patients will receive TRC105 treatment on Days 1, 8, and 15 and bevacizumab treatment on Day 1 of each 21-day cycle.

TRC105 and Bevacizumab

Charles P Theuer, MD

The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.

Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105, a monoclonal antibody to CD105, is a novel angiogenesis inhibitor that complements bevacizumab in preclinical models. Together, these antibodies may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab alone. The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.

Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated

An Open Label Phase 1B Dose-Escalation Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors

Three patients will be initially enrolled and treated at each dose level. If none of these 3 patients experiences a dose-limiting toxicity (DLT) during the 28-day evaluation period, dose escalation will proceed following review of safety data with appropriate site staff including the principal investigators at all sites. If 1 of 3 patients experiences DLT, the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will have been exceeded if ≥ 33% of patients experience DLT in a given cohort. DLT will have occurred when a patient has 1 or more toxicity listed in the table below that is at least possibly related to the combination of bevacizumab and TRC105 during the first 28 days (cycle 1).

Plasma TRC105 concentrations will be measured at specified timepoints.

HAMA and HACA titers will be measured at specified time-points.

The best response according to RECIST 1.1 for each patient with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type

Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.

Prior VEGF inhibitor treatment

No prior VEGF inhibitor treatment

Dr Charles Theuer

Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab

TRC105 Pharmacokinetic Concentrations

HAMA POSITIVE

HAMA NEGATIVE

HACA POSITIVE

HACA NEGATIVE

Immune Response to TRC105

RECIST 1.1 defined response

Tumor burden decreases

Objective Response According to RECIST 1.1

Digestive System Diseases

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Antibodies, Monoclonal

Liver Extracts

Sorafenib

TRC105 is an experimental cancer drug designed to slow or stop the growth of tumors. It does this by preventing the growth of new blood vessels that feed these tumors. This drug is being used to test the safety and effectiveness to treat liver cancer that has not responded to standard therapy. TRC105 will be given as an intravenous infusion every two weeks.

Tim F Greten, M.D.

Background:

- TRC105 is an experimental cancer drug. It is designed to slow or stop the growth of tumors. It does this by preventing the growth of new blood vessels that feed these tumors. People with hepatocellular carcinoma (or liver cancer) sometimes do not respond to standard treatments. This includes the cancer drug sorafenib.

Objectives:

- To test the safety and effectiveness of TRC105 to treat liver cancer that has not responded to standard therapy.

Eligibility:

* People at least 18 years of age who have hepatocellular carcinoma (or liver cancer) that has not responded to standard therapy. Participants also will not be eligible for a liver transplant.
* No anticoagulation therapy is allowed with the exception of low-dose aspirin.
* No history of bleeding disorders, peptic ulcer disease or gastritis.

Design:

* Participants will have a physical exam and medical history. They will also have blood and urine tests, and imaging studies.
* Participants will receive TRC105 once a week. They will also have two daily doses of a steroid the day before each treatment. This will help prevent known side effects.
* Participants will be monitored with blood and urine tests. They will also have imaging studies every two months to study the effect of the drug on tumor growth.
* Participants will continue to have TRC105 as long as they do not have severe side effects and their liver cancer stops growing or shrinks. After stopping TRC105, they will have yearly visits with physical exams and blood tests.

Background:

* Worldwide, hepatocellular carcinoma (HCC) is the fifth most common malignancy with a median survival of 6-9 months. The Study of Heart and Renal Protection (SHARP) study established Sorafenib as a standard consideration in this disease and set the bar for future studies of systemic therapy. There is no standard therapy for patients whose disease has progressed despite Sorafenib therapy.
* TRC105 is a chimeric, anti-angiogenic monoclonal antibody that binds CD105, a transmembrane receptor overexpressed by proliferating endothelial cells. TRC105 binds to CD105-expressing endothelial cells and mediates growth inhibition, apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC).

Objectives:

Primary:

-To evaluate time to tumor progression (TTP) for TRC105 in HCC.

Secondary:

* To evaluate safety of TRC105 in HCC.
* To evaluate the immunogenicity of TRC105 as measured by human antichimeric antibody (HACA) and human antimouse antibody formation.
* To evaluate anti-tumor response as determined by standard and European Association for the Study of the Liver (EASL) -modified Response Evaluation Criteria in Solid Tumors (RECIST) response criteria.
* To perform correlative studies assessing potential biomarkers of response to TRC105.

Eligibility:

* Histologically or cytologically confirmed diagnosis of HCC.
* Childs-Pugh A or B (7 points) cirrhosis only is allowed.
* Patients must have disease that is not amenable to potentially curative resection.
* Patients must have progressed on or been intolerant of prior sorafenib therapy.
* No history of bleeding varices (unless subsequent liver transplant). All patients must have had endoscopic evaluation within 6 months of starting study.
* No history of bleeding varices in previous 1 year (unless subsequent liver transplant). No anti-coagulation (except low-dose aspirin).

Design:

* This is a single-arm phase II study of TRC105 in patients with HCC.
* TRC105 will be administered as an intravenous infusion every two weeks. Patients will be re-staged every 8 weeks.
* The primary endpoint of the study will be Time to Tumor Progression (TTP). The primary purpose of this study is to evaluate the ability of TRC105 as a second line treatment to improve upon the time to progression (TTP) of patients with refractory HCC.

TRC105 for Liver Cancer That Has Not Responded to Sorafenib

A Phase II Study of TRC105 in Patients With Hepatocellular Carcinoma (HCC) Who Have Progressed on Sorafenib

Time to tumor progression is defined as the proportion of participants who are progression free after 4 months on study. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progressions).

here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

National Cancer Institute (NCI)

Principal Investigator

TRC105 in Liver Cancer

Age, Categorical

Dr. Tim Greten

Time to Tumor Progression (TTP) for TRC105 in Hepatocellular Carcinoma (HCC).

Count of Participants With Adverse Events

Amino Acids

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Carotuximab (TRC105) in combination with standard dose Sorafenib.

Bi-weekly iv TRC105 (15 mg/kg) will be given with 400mg sorafenib twice daily in the phase 1B portion of the study. Weekly iv TRC105 (10 mg/kg) will be given with 400mg sorafenib twice daily in the phase 2 portion of the study.

Carotuximab (TRC105)

400 mg of sorafenib will be given twice daily.

The purpose of the phase 1b portion is to evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose sorafenib in patients with hepatocellular carcinoma. Up to 18 patients will be treated.

The purpose of the phase 2 portion is to estimate the ORR of patients with hepatocellular carcinoma by RECIST 1.1. Up to 21 patients will be treated in phase 2.

Sorafenib is an oral multikinase inhibitor targeting several receptor tyrosine kinases, including the VEGF receptor (VEGFR), implicated in pathologic angiogenesis, tumor growth, and cancer progression. Sorafenib is approved for the treatment of unresectable hepatocellular carcinoma (HCC). TRC105 is an antibody to endoglin, an important angiogenic target on proliferating endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR in preclinical models. Together, the use of TRC105 with sorafenib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with sorafenib alone.

Trial of TRC105 and Sorafenib in Patients With HCC

An Open Label Phase 1B/2 Trial of TRC105 and Sorafenib in Patients With Hepatocellular Carcinoma (HCC)

If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC105 during the first 4 months of participation in the trial. The number of DLTs by dose cohort have been presented.

Number of patients with a response (PR or CR) are included by dose level. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients must have had a screening scan and at least 1 on study scan to be eligible for RECIST 1.1 evaluation.

Steady state mean trough serum concentrations by dose level of TRC105 after 5 weeks of dosing were measured using validated methods after 5 weeks of dosing.

Number of patients who tested positive for antibodies to TRC105 by dose level. Anti-Product Antibody (APA) concentrations were measured using validated ELISA methods.

Only patients who received at least a portion of a dose of TRC105 or sorafenib were included in the safety population. Both dose groups received 10 mg/kg TRC105 for the first month. Patients assigned to the 10 mg/kg weekly (cycle 1) then 15 mg/kg every two weeks (cycle 2+) dose group who discontinued the study prior to initiating cycle 2 dosing were counted in the 10 mg/kg weekly adverse event group.

Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily

Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib

Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily

Carotuximab (10 mg/kg Weekly) Plus Sorafenib

Total

Asian

White

Black or African American

Unknown

Race/Ethnicity, Customized

Patients who received at least a portion of a dose of Carotuximab

TRC105 development has been discontinued due to lack of efficacy. Secondary endpoints including PFS, OS, duration of response, sorafenib PK, circulating angiogenic biomarkers and assessment of IGF-1-modified Child-Pugh score were not performed.

Charles Theuer

Patients must have received at least a portion of a dose of TRC105 or sorafenib to be evaluable for assessment of DLT.

Number of Patients Who Experience Dose Limiting Toxicities by Dose Level

Patients must have had a screening scan and at least 1 on study scan to be eligible for RECIST 1.1 evaluation.

Overall Response Rate (ORR)

Steady state mean trough serum concentration by dose level after 5 weeks of dosing. Patients must have received all protocol required TRC105 doses to be included in the analysis. Additional analysis were not performed as TRC105 development overall was canceled due to lack of efficacy.

Pharmacokinetic Profile of TRC105 When Given With Sorafenib

Number of patients who tested positive for antibodies to TRC105. Patients must have tested negative for TRC105 antibodies at baseline and have had an on study test performed to be included in the analysis.

TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA)

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

Anti-Infective Agents

Carbamide Peroxide

Immunologic Factors

TRC105 is a human/murine chimeric IgG1 antibody administered i.v. every two weeks (on days 1 and 15) or weekly (on days 1, 8, 15 and 22) of each 28 day cycle; until progression or unacceptable toxicity develops.

TRC105 chimeric anti-CD105 antibody

Bryan R Leigh, MD

This study is being performed to evaluate the safety and tolerability of the TRC105 monoclonal antibody.

In addition to safety, this study will also evaluate pharmacokinetics, tumor response and anti-TRC105 antibody formation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)	NCT02664961	Gestational Tro... Choriocarcinoma Placental Site ... Epithelioid Tro...	TRC105 Bevacizumab	16 Years - 99 Years	Tracon Pharmaceuticals Inc.
Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated	NCT01332721	Adult Solid Tum...	TRC105 and Beva...	18 Years -	Tracon Pharmaceuticals Inc.
Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated	NCT01332721	Adult Solid Tum...	TRC105 and Beva...	18 Years -	Tracon Pharmaceuticals Inc.
TRC105 for Liver Cancer That Has Not Responded to Sorafenib	NCT01375569	Hepatocellular ... Hepatocellular ... Carcinoma, Hepa...	TRC105	18 Years - 80 Years	National Institutes of Health Clinical Center (CC)
Trial of TRC105 and Sorafenib in Patients With HCC	NCT02560779	Hepatocellular ...	Carotuximab (TR... Sorafenib	18 Years -	Tracon Pharmaceuticals Inc.
Open Label Phase 1 Dose Finding Study of TRC105 in Patients With Solid Cancer	NCT00582985	Cancer Neoplasm Metast...	TRC105 chimeric...	18 Years -	Tracon Pharmaceuticals Inc.
TRC105 for Liver Cancer That Has Not Responded to Sorafenib	NCT01375569	Hepatocellular ... Hepatocellular ... Carcinoma, Hepa...	TRC105	18 Years - 80 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for cd105

Every month we try and update this database with for cd105 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cd105

Every month we try and update this database with for cd105 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cd105 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.