TRC105 Combined With Standard-dose Bevacizumab for Two Patients With Metastatic And Refractory Choriocarcinoma

• Sponsor: Tracon Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02396511
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 35
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether TRC105 in combination with Bevacizumab is effective in the treatment of two patients with metastatic and refractory choriocarcinoma.

Condition or Disease	Intervention/Treatment	Phase
Choriocarcinoma	Biological: TRC105; Biological: Bevacizumab	Phase 2

Detailed Description

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 is a monoclonal antibody to CD105, an angiogenic target highly expressed on the tumor vessels and the tumor cells in choriocarcinoma. Together, these antibodies may be efficacious in metastatic and refractory choriocarcinoma, a tumor type that is highly vascular and expresses endoglin. The purpose of this study is to determine whether TRC105 in combination with Bevacizumab is effective in the treatment of two patients with metastatic and refractory choriocarcinoma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Patient Treatment Protocol of TRC105 Combined With Standard-dose Bevacizumab for Two Patients With Metastatic And Refractory Choriocarcinoma
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TRC105 and Bevacizumab TRC105 weekly intravenous infusion bevacizumab every 2 weeks intravenous infusion	Biological: TRC105; weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops; Other Names: Chimeric Antibody (TRC105) to CD105 ; Biological: Bevacizumab; Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival of Two Patients With Metastatic and Refractory Choriocarcinoma [Assessed every 8 weeks for up to 35 Months]

   Progression Free Survival of Two Patients With Metastatic and Refractory Choriocarcinoma determined according to RECIST 1.1 including measurement of serum β- hCG. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. A 5 mm absolute increase is also required to guard against over calling PD when the total sum is very small.

2. Objective Response Rate of Two Patients With Metastatic and Refractory Choriocarcinoma by RECIST 1.1 Including Measurement of Serum β- hCG [Assessed every 8 weeks for up to 35 Months]

   To determine the Objective Response Rate of two patients with metastatic and refractory choriocarcinoma by RECIST 1.1 including measurement of serum β- hCG. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) categorizes response as: 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

Secondary Outcome Measures

1. Frequency and Severity of Adverse Events [Assessed weekly during and up to 28 days after completion of study protocol over a maximum period of 35 months.]

   Adverse event frequency and severity according to CTCAE version 4.0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Willingness and ability to consent for self to participate in study

2. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

3. Measurable disease by RECIST 1.1 and elevated serum β-hCG

4. Histologically proven choriocarcinoma that has progressed despite all described lines of chemotherapy for this condition

Exclusion Criteria:

1. Prior treatment with TRC105

2. Serious dose-limiting toxicity related to prior bevacizumab

3. Current treatment on another therapeutic clinical trial

4. Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry is allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)

5. Symptomatic pericardial or pleural effusions

6. Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks

7. Active bleeding or pathologic condition that carries a high risk of bleeding (i.e. hereditary hemorrhagic telangiectasia)

8. Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy

9. Cardiac dysrhythmias of NCI CTCAE grade ≥ 2 within the last 28 days

10. Known active viral or nonviral hepatitis

11. Open wounds or unhealed fractures within 28 days of starting study treatment

12. History of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment

13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Insititue	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Tracon Pharmaceuticals Inc.

Investigators

• Study Director: Charles Theuer, MD, Medical Monitor

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 17, 2015

More Information

Publications

None provided.

• Responsible Party: Tracon Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT02396511
• Other Study ID Numbers: 105CC201 & 105CC201B
• First Posted: Mar 24, 2015
• Last Update Posted: Jun 11, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Choriocarcinoma; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	TRC105 and Bevacizumab
Arm/Group Description	TRC105 weekly intravenous infusion bevacizumab every 2 weeks intravenous infusion TRC105: weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops Bevacizumab: Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	TRC105 and Bevacizumab
Arm/Group Description	TRC105 weekly intravenous infusion bevacizumab every 2 weeks intravenous infusion TRC105: weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops Bevacizumab: Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops
Overall Participants	2
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	39.5
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 50%
Not Hispanic or Latino	1 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 50%
More than one race	0 0%
Unknown or Not Reported	1 50%
Region of Enrollment (participants) [Number]
United States	2 100%
Number of Prior Regimens (prior regimens) [Median (Full Range) ]
Median (Full Range) [prior regimens]	7

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival of Two Patients With Metastatic and Refractory Choriocarcinoma
Description	Progression Free Survival of Two Patients With Metastatic and Refractory Choriocarcinoma determined according to RECIST 1.1 including measurement of serum β- hCG. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. A 5 mm absolute increase is also required to guard against over calling PD when the total sum is very small.
Time Frame	Assessed every 8 weeks for up to 35 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TRC105 and Bevacizumab
Arm/Group Description	TRC105 weekly intravenous infusion bevacizumab every 2 weeks intravenous infusion TRC105: weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops Bevacizumab: Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops
Measure Participants	2
Mean (Full Range) [Months]	18

2. Primary Outcome

Title	Objective Response Rate of Two Patients With Metastatic and Refractory Choriocarcinoma by RECIST 1.1 Including Measurement of Serum β- hCG
Description	To determine the Objective Response Rate of two patients with metastatic and refractory choriocarcinoma by RECIST 1.1 including measurement of serum β- hCG. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) categorizes response as: 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
Time Frame	Assessed every 8 weeks for up to 35 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TRC105 and Bevacizumab
Arm/Group Description	TRC105 weekly intravenous infusion bevacizumab every 2 weeks intravenous infusion TRC105: weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops Bevacizumab: Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops
Measure Participants	2
Response	1 50%
Progression	1 50%

3. Secondary Outcome

Title	Frequency and Severity of Adverse Events
Description	Adverse event frequency and severity according to CTCAE version 4.0.
Time Frame	Assessed weekly during and up to 28 days after completion of study protocol over a maximum period of 35 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TRC105 and Bevacizumab
Arm/Group Description	TRC105 weekly intravenous infusion bevacizumab every 2 weeks intravenous infusion TRC105: weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops Bevacizumab: Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops
Measure Participants	2
Total SAE's	4
TRC105 Related SAEs	3

Adverse Events

Time Frame	Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to a maximum period of 35 months.
Arm/Group Title	TRC105 and Bevacizumab
Arm/Group Description	TRC105 weekly intravenous infusion bevacizumab every 2 weeks intravenous infusion TRC105: weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops Bevacizumab: Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops
All Cause Mortality
	TRC105 and Bevacizumab
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	TRC105 and Bevacizumab
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
General disorders
Malaise	1/2 (50%)	1
Injury, poisoning and procedural complications
Infusion Related Reaction	1/2 (50%)	1
Nervous system disorders
Headache	1/2 (50%)	1
Migraine	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	TRC105 and Bevacizumab
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Blood and lymphatic system disorders
Anaemia	1/2 (50%)	1
Eye disorders
Periorbital oedema	1/2 (50%)	1
Gastrointestinal disorders
Gingival Bleeding	1/2 (50%)	1
Glossodynia	1/2 (50%)	1
Gingival Pain	1/2 (50%)	4
Abdominal pain upper	1/2 (50%)	1
Vomiting	1/2 (50%)	1
General disorders
Pyrexia	1/2 (50%)	1
Fatigue	2/2 (100%)	4
Mucosal Inflammation	1/2 (50%)	1
Chest discomfort	1/2 (50%)	1
Malaise	1/2 (50%)	1
Infections and infestations
Urinary tract infection	1/2 (50%)	1
Oral Viral Infection	1/2 (50%)	1
Gingival Infection	1/2 (50%)	4
Injury, poisoning and procedural complications
Infusion related reaction	1/2 (50%)	2
Investigations
Blood alkaline phosphatase increased	1/2 (50%)	1
Metabolism and nutrition disorders
Hypomagnesaemia	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/2 (50%)	1
Muscular Weakness	1/2 (50%)	1
Pain In Extremity	1/2 (50%)	1
Nervous system disorders
Headache	1/2 (50%)	1
Migraine	1/2 (50%)	4
Dizziness	1/2 (50%)	2
Psychiatric disorders
Anxiety	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/2 (50%)	1
Epistaxis	1/2 (50%)	1
Dysphonia	1/2 (50%)	1
Cough	1/2 (50%)	1
Oropharyngeal Pain	1/2 (50%)	1
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	1/2 (50%)	1
Rash	1/2 (50%)	2
Vascular disorders
Hypertension	1/2 (50%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.