Lung CancerPhase 1NCT02429843
A Study of TRC105 in Combination With Paclitaxel/Carboplatin and Bevacizumab in Non-Squamous Cell Lung Cancer
A Phase 1 study testing TRC105 in people with Lung Cancer, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- TRC105
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2015to Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
- History of peptic ulcer disease or erosive gastritis within the past 3 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment.
- History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair).
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
- Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.: hysterectomy) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to first dose. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35233
About this study
Official title: A Phase 1B Dose-Escalation Study of TRC105 in Combination With Paclitaxel/Carboplatin and Bevacizumab in Patients With Stage 4 Non-Squamous Cell Lung Cancer
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.
Read the detailed description
Advanced non-small cell lung cancer has been historically difficult to treat, and novel agents are in dire need.TRC105 has been shown to enhance the anti-angiogenic effect of bevacizumab and may result in more effective angiogenesis inhibition and improved clinical efficacy when combined with bevacizumab and paclitaxel/carboplatin. Participants will be treated with the combination drugs for 6 cycles of therapy (3 weeks per cycle) and may or may not be placed on maintenance therapy depending upon the induction response. Maintenance therapy will continue until there is disease progression, unacceptable toxicity, or patient withdrawal. Blood collections and tumor assessments will be performed throughout the study.
- Conditions
- Lung Cancer
- Being tested
- TRC105
- Keywords
- Non-squamous cell lung cancer, Non-squamous non-small cell lung cancer, vascular endothelial growth factor (VEGF), TRC105
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRC105Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: TRC105 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to 28 days after the last cycle
Secondary outcomes (7)
Measurement of tumor response
Radiological tumor assessments from CT or MRI scans will be used to determine an objective response rate.
Measured: Baseline to 3 years
Progression-free survival
Time to progressive disease
Measured: Baseline to 3 years
Number of patients with progression-free survival at 6 months
The percentage of patients with progression-free survival in the study
Measured: 6 months after the last cycle of treatment completed
Overall survival
Length of patient survival after starting study treatment
Measured: Baseline to 3 years
Measurement of TRC105 concentrations
Serum TRC105 concentrations will be measured using validated enzyme-linked immunoassay testing that will assist in analyzing the pharmacokinetics of the drug.
Measured: Collected approximately every 63 days (3 cycles)
Measurement of TRC105 anti-product antibodies
Anti-product antibody concentrations will be measured using validated enzyme-linked immunoassay testing that will assist in analyzing immunogenicity.
Measured: Collected approximately every 63 days (3 cycles)
Identify angiogenic protein biomarkers
A central reference lab will conduct biomarker testing that will assist in the analysis of the pharmacodynamics effects on circulating angiogenic biomarkers.
Measured: Collected approximately every 63 days (3 cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study start2 Nov 2015
- Primary completionDec 2018
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Tracon Pharmaceuticals Inc.
- Responsible party
- Principal investigator, Francisco Robert,MD, University of Alabama at Birmingham
- Investigators
- Francisco Robert, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02429843
- Sponsor's protocol ID
- F150128005 (UAB 1504)
- Status last verified
- Jun 2021
- First submitted
- 18 Mar 2015
- Last updated
- 28 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B Dose-Escalation Study of TRC105 in Combination With Paclitaxel/Carboplatin and Bevacizumab in Patients With Stage 4 Non-Squamous Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02429843
- Acronym / sponsor ID
- F150128005 (UAB 1504)
- Conditions
- Lung Cancer
- Keywords
- Non-squamous cell lung cancer, Non-squamous non-small cell lung cancer, vascular endothelial growth factor (VEGF), TRC105
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Tracon Pharmaceuticals Inc.
- Study start
- 2 Nov 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 29 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Advanced non-small cell lung cancer has been historically difficult to treat, and novel agents are in dire need.TRC105 has been shown to enhance the anti-angiogenic effect of bevacizumab and may result in more effective angiogenesis inhibition and improved clinical efficacy when combined with bevacizumab and paclitaxel/carboplatin. Participants will be treated with the combination drugs for 6 cycles of therapy (3 weeks per cycle) and may or may not be placed on maintenance therapy depending upon the induction response. Maintenance therapy will continue until there is disease progression, unacceptable toxicity, or patient withdrawal. Blood collections and tumor assessments will be performed throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Standard treatment + TRC105 | Experimental | Drug: TRC105In 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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).
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TRC105Each 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. | Drug | Standard treatment + TRC105 |
Primary outcome
Number of patients with a change in medical management
Time frame: Baseline up to 28 days after the last cycle
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.
7 secondary outcomes
Measurement of tumor response
Time frame: Baseline to 3 years
Progression-free survival
Time frame: Baseline to 3 years
Number of patients with progression-free survival at 6 months
Time frame: 6 months after the last cycle of treatment completed
Overall survival
Time frame: Baseline to 3 years
Measurement of TRC105 concentrations
Time frame: Collected approximately every 63 days (3 cycles)
Measurement of TRC105 anti-product antibodies
Time frame: Collected approximately every 63 days (3 cycles)
Identify angiogenic protein biomarkers
Time frame: Collected approximately every 63 days (3 cycles)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco Robert, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TRC105 in people with Lung Cancer, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with a change in medical management (time frame: Baseline up to 28 days after the last cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2021.