Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Adult Solid Tumor |
Drug: TRC105 and Bevacizumab |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | An Open Label Phase 1B Dose-Escalation Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors |
- Determine Maximum Tolerated Dose of TRC105 in Combination with Bevacizumab [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]Safety and dose limiting toxicity will be assessed by dose cohort.
- TRC105 Pharmacokinetic Concentrations [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]Plasma TRC105 concentrations will be measured at specified timepoints.
- Immune Response to TRC105 [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]HAMA and HACA titers will be measured at specified time-points.
- Objective response according to RECIST 1.1 [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]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
| Estimated Enrollment: | 24 |
| Study Start Date: | April 2011 |
| Estimated Study Completion Date: | March 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: TRC105 and Bevacizumab
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.
|
Drug: TRC105 and Bevacizumab
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.
Other Names:
|
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, 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically proven advanced or metastatic solid cancer
- Measurable disease, evaluable disease or elevation of a relevant soluble tumor marker (e.g., CEA, PSA, CA125)
- Age of 18 years or older
- ECOG performance status of 0 or 1
- Resolution of all acute AEs resulting from prior cancer therapies to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
- Adequate organ function
- Willing and able to consent for self to participate in study
Exclusion Criteria:
- Prior treatment with TRC105
- Serious dose-limiting toxicity related to prior bevacizumab
- Current treatment on another therapeutic clinical trial
- Receipt of an investigational agent within 28 days of starting study treatment
- Prior surgery (including open biopsy) within 28 days of starting the study treatment
- Prior radiation therapy or systemic therapy within 21 days of starting the study treatment
- Minor surgical procedures such as fine needle aspirations, Mediport placement or core biopsies within 7 days of study treatment
- Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)
- Symptomatic pericardial or pleural effusions
- Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks
- History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease (except in the expansion cohort at the MTD where brain metastases or primary brain tumors are eligible)
- Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
- Active bleeding or pathologic condition that carries a high risk of bleeding
- Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
- Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last 28 days
- Known active viral or nonviral hepatitis
- Centrally located non-small cell lung cancer (regardless of histologic sub-type), or non-small cell lung cancer of squamous histology.
- History of hemorrhage or hemoptysis (>½ teaspoon bright red blood) within 6 months of starting study treatment
- Open wounds or unhealed fractures within 28 days of starting study treatment
- 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
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Pregnancy or breastfeeding
Contacts and Locations| Contact: Bonne Adams, MBA | 858 550 0780 ext 228 | badams@traconpharma.com |
| Contact: Delia Alvarez | 858 550 0780 ext 232 | dalvarez@traconpharma.com |
| United States, Alabama | |
| University of Alabama at Birmingham | Recruiting |
| Birmingham, Alabama, United States, 35249 | |
| Principal Investigator: Francisco Robert, MD | |
| United States, Arizona | |
| Pinnacle Oncology Hematology | Recruiting |
| Scottsdale, Arizona, United States, 85258 | |
| Principal Investigator: Michael S Gordon, MD | |
| United States, California | |
| Premiere Oncology | Recruiting |
| Santa Monica, California, United States, 90404 | |
| Principal Investigator: Lee Rosen, MD | |
| United States, Indiana | |
| Indiana University Simon Cancer Center | Recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Principal Investigator: E. Gabriela Chiorean, MD | |
| Study Director: | Bryan R Leigh, MD | Tracon Pharmaceuticals Inc. |
More Information
No publications provided
| Responsible Party: | Tracon Pharmaceuticals Inc. |
| ClinicalTrials.gov Identifier: | NCT01332721 History of Changes |
| Other Study ID Numbers: | 105ST102 |
| Study First Received: | April 7, 2011 |
| Last Updated: | December 10, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Tracon Pharmaceuticals Inc.:
|
TRC105 CD105 Endoglin |
Solid Tumors Avastin Bevacizumab |
Additional relevant MeSH terms:
|
Neoplasms Bevacizumab Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances |
Physiological Effects of Drugs Pharmacologic Actions Growth Inhibitors Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 19, 2013