A Study of TRC105 in Combination With Paclitaxel/Carboplatin and Bevacizumab in Non-Squamous Cell Lung Cancer

NCT02429843 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: F150128005 (UAB 1504)
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open-label, nonrandomized, phase 1b study of TRC105 in combination with standard dose treatment in patients with stage IV non-squamous non-small cell lung cancer.

Conditions

Lung Cancer

Keywords

Non-squamous cell lung cancer; Non-squamous non-small cell lung cancer; vascular endothelial growth factor (VEGF); TRC105

Outcome Measures

Primary Outcomes (1)

• Number of patients with a change in medical management

  Adverse events will be graded using the NCI Common Terminology for Criteria for Adverse Events(CTCAE). Incidence, timing, and relatedness of adverse events will be considered as factors in the change of a patient's medical management.

  Baseline up to 28 days after the last cycle

Secondary Outcomes (7)

• Measurement of tumor response

  Baseline to 3 years

• Progression-free survival

  Baseline to 3 years

• Number of patients with progression-free survival at 6 months

  6 months after the last cycle of treatment completed

• Overall survival

  Baseline to 3 years

• Measurement of TRC105 concentrations

  Collected approximately every 63 days (3 cycles)

Study Arms (1)

Standard treatment + TRC105

EXPERIMENTAL

In addition to standard treatment of paclitaxel, carboplatin, and bevacizumab, dosing of TRC105 will begin at 8 mg/kg. However a lower dose level has also been included (6 mg/kg) and will be enrolled if 8 mg/kg is found to exceed the maximum tolerated dose. Following the appropriate pre-medication regimen, the first weekly TRC105 dose (cycle 1 day 8) will be split into two doses whereby 3 mg/kg is administered on cycle 1 day 8 and the balance (e.g., 5 mg/kg for Dose Level 1) is administered on cycle 1 day 11. Beginning with cycle 1 day 15 and thereafter, the full TRC105 dose will be administered intravenously each week during the 21-day cycle. Intra-patient dose reductions are allowed beginning in cycle 2.

Drug: TRC105

Interventions

TRC105 DRUG

Each patient will be dosed with 6, 8, or 10 mg/kg of TRC105 up to a maximum dose of 850 mg for women and 1,000 mg for men based upon overall body weight.

Standard treatment + TRC105

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment-naïve, stage 4 Non-Squamous Cell Lung Cancer
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST).
• Age of 19 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Resolution of all acute adverse events resulting from prior cancer therapies to NCI Common Terminology Criteria for Adverse Events (CTCAE) grade ≤1 or baseline (except alopecia or neuropathy).
• Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST; serum glutamate oxaloacetate transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamate pyruvate transaminase \[SGPT\]) ≤2.5 x upper limit of normal (ULN) or ≤5 x ULN in cases of liver metastases.
• Total serum bilirubin ≤1.5 times the upper limit of normal.
• Absolute neutrophil count (ANC) ≥1500/μL.
• Platelets ≥100,000/μL without transfusion support within the past 28 days.
• Hemoglobin ≥9.0 g/dL without transfusion support within the past 28 days (erythropoietin or darbepoietin 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) from 0.8 to 1.2.
• Willingness and ability to consent for self to participate in study.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Non-small cell lung cancer of squamous histology.
• Prior treatment with TRC105.
• Current treatment on another therapeutic clinical trial.
• Receipt of a small molecule anticancer agent, including an investigational anticancer small molecule, within 14 days of starting study treatment.
• Receipt of a large molecule anticancer agent (e.g., antibody), including an investigational anticancer antibody, within 28 days of starting study treatment.
• No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months. The following are not considered to be major procedures and are permitted up to 7 days before therapy initiation: thoracentesis, paracentesis, port placement, laparoscopy, thorascopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures.
• 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 study registration or those patients who have not recovered adequately from side effects of such therapy.
• Uncontrolled chronic hypertension defined as systolic \>150 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).
• 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.
• Angina, myocardial ischemia (MI), 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 the past 6 months. Deep venous thrombosis within 6 months, unless the patient is anticoagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.
• Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia). Patients who have been uneventfully anticoagulated with low molecular weight heparin are eligible.
• Thrombolytic use (except to maintain i.v. catheters) or anticoagulant use 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 or cirrhosis.
• History of hemorrhage or hemoptysis (\>½ teaspoon bright red blood) within 3 months of starting study treatment.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Tracon Pharmaceuticals Inc.: collaborator

Study Sites (1)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

carotuximab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Francisco Robert, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: April 29, 2015
• Study Start: November 2, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: June 28, 2021

Record last verified: 2021-06

Locations

US (1)