A trial in people with advanced angisarcoma to compare the effects of treatment with an investigational medicine, TRC105, and pazopanib against the effects of pazopanib used by itself.
- Conditions
- Advanced angiosarcomaMedDRA version: 20.0 Level: PT Classification code 10002476 Term: Angiosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000485-34-FR
- Lead Sponsor
- TRACON Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 200
1. Histologically-confirmed angiosarcoma that is not amenable to curative intent surgery (e.g., metastatic or bulky disease and disease for which surgical resection would carry an unacceptable risk to the patient). Pathology report will be reviewed by sponsor prior to randomization.
2. Documented progression on or following most recent systemic chemotherapy regimen (not required for chemotherapy-naïve patients), within 4 months prior to screening
3. Measurable disease by RECIST v1.1
4. Age of 18 years or older; in addition, patients age 12 to 17 years may enroll beginning in Cohort 2 if weight = 40 kg
5. Eastern Cooperative Oncology Group (ECOG) performance status = 1
6. Resolution of all acute AEs resulting from prior cancer therapies to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) grade = 1 or to that patient’s pre-study baseline (except alopecia or neuropathy)
7. Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT])
and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) = 2.5 x upper limit of normal (ULN) or = 5 x ULN in cases of liver metastases
• Total serum bilirubin = 1.5 x ULN
• Absolute neutrophil count (ANC) = 1500/µL
• Platelets = 100,000/µL (without transfusion support within 28 days prior to randomization)
• Hemoglobin = 9.0 g/dL (without transfusion support within 14 days prior to randomization; erythropoietin or darbepoetin permitted)
• Serum creatinine = 1.5 times the upper limit of normal or creatinine clearance > 30 mL/min by Cockcroft-Gault formula
• International normalized ratio (INR) = 1.2
8. Willingness and ability to consent (and assent if under age 18) for self to participate in study
9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
10. Angiosarcoma tumor specimen, if available
11. Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use a condom with spermicide and to not donate sperm during the study and for at least 180 days following last dose of TRC105 or pazopanib
12. Woman of non-child bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause (i.e., no menstrual bleeding for more than 12 months in a 1 or to that patient’s pre-study baseline (except alopecia or neuropathy) women aged 45 years or more), OR woman of child bearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test and agree to use at least 2 acceptable methods of birth control, one of which must be highly effective, during the study and for at least 180 days after stopping TRC105 or pazopanib
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
1. Prior treatment with TRC105
2. Prior treatment with any VEGF inhibitor
3. More than two prior lines (may be combination regimens) of chemotherapy for angiosarcoma (neoadjuvant/adjuvant treatment does not count as a line of treatment)
4. Current treatment or participation on another therapeutic clinical trial
5. Women who are pregnant or breastfeeding
6. Receipt of systemic anticancer therapy, including investigational agents, within 5 times the agent’s elimination half-life of starting study treatment
7. Major surgical procedure or significant traumatic injury within 4 weeks prior to randomization and must have fully recovered from any such procedure or injury; planned surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months. Note: the following are not considered to be major procedures and are permitted up to 7 days before randomization: Thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, and imaging-guided biopsy for diagnostic purposes
8. Patients who have received wide field radiotherapy = 28 days (defined as > 50% of volume of pelvic bones or equivalent) or limited field radiation for palliation < 14 days prior to randomization
9. Uncontrolled hypertension defined as systolic > 150 or diastolic > 100 mm Hg on the average of the 3 most recent BP readings. Anti-hypertensives may be started prior to randomization.
10. Ascites or pleural effusion requiring intervention or that required intervention or recurred within three months prior to randomization
11. Pericardial effusion (except trace effusion identified by echocardiogram) within three months prior to randomization
12. History of 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 prior to randomization
13. Angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism , pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within 6 months prior to randomization. Deep venous thrombosis within 3 months prior to randomization unrelated to a central venous catheter, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks prior to randomization. In this situation, low molecular weight heparin is preferred
14. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia). Patients with bleeding cutaneous lesions not actively requiring transfusions are eligible. Patients who have been uneventfully anti-coagulated with low
molecular weight heparin are eligible
15. Hemoptysis (> ½ teaspoon [2.5 mL] of bright red blood) within 6 months prior to randomization
16. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to randomiz
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method