Choriocarcinoma
Conditions
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.
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.
Interventions
BIOLOGICALTRC105
weekly i.v. TRC105 in combination with every 2 weeks i.v.bevacizumab, until progression or unacceptable toxicity develops
BIOLOGICALBevacizumab
Every 2 weeks i.v.bevacizumab in combination with weekly i.v. TRC105, until progression or unacceptable toxicity develops
Sponsors
Tracon Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TRC105 and Bevacizumab 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 | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | TRC105 and Bevacizumab |
|---|---|
| Age, Continuous | 39.5 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of Prior Regimens | 7 prior regimens |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 |
Outcome results
Primary
Objective Response Rate of Two Patients With Metastatic and Refractory Choriocarcinoma by RECIST 1.1 Including Measurement of Serum β- hCG
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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TRC105 and Bevacizumab | Objective Response Rate of Two Patients With Metastatic and Refractory Choriocarcinoma by RECIST 1.1 Including Measurement of Serum β- hCG | Response | 1 Participants |
| TRC105 and Bevacizumab | Objective Response Rate of Two Patients With Metastatic and Refractory Choriocarcinoma by RECIST 1.1 Including Measurement of Serum β- hCG | Progression | 1 Participants |
Primary
Progression Free Survival of Two Patients With Metastatic and Refractory Choriocarcinoma
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TRC105 and Bevacizumab | Progression Free Survival of Two Patients With Metastatic and Refractory Choriocarcinoma | 18 Months |
Secondary
Frequency and Severity of Adverse Events
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TRC105 and Bevacizumab | Frequency and Severity of Adverse Events | Total SAE's | 4 Events |
| TRC105 and Bevacizumab | Frequency and Severity of Adverse Events | TRC105 Related SAEs | 3 Events |