Verified June 2017 by Tracon Pharmaceuticals Inc.
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.
First received: June 1, 2017
Last updated: June 6, 2017
Last verified: June 2017
This is a multicenter, open-label, nonrandomized, Phase 1b, dose-escalation study of Carotuximab (also known as TRC105) in combination with standard dose Nivolumab in patients with metastatic NSCLC.
|Carcinoma, Non-Small-Cell Lung||Drug: Carotuximab
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1b Dose-Escalation Study of Carotuximab in Combination With Nivolumab in Patients With Metastatic Non-Small Cell Lung Cancer|
- Response rate [ Time Frame: Approximately 2-8 months ]
Preliminary evidence of antitumor activity of carotuximab plus nivolumab will be evaluated, by assessing response rate.
- Trough carotuximab concentrations [ Time Frame: Approximately 2-8 months ]
Trough (pre-dose) serum carotuximab concentrations will be measured using validated ELISA methods.
- Development of immunogenicity antibodies [ Time Frame: Approximately 2-8 months ]
The formation of carotuximab anti-product antibodies (APA) will be evaluated.
- Progression-free survival [ Time Frame: Approximately 2-8 months ]
Preliminary evidence of antitumor activity of carotuximab plus nivolumab will be evaluated, by assessing progression-free survival.
- Trough nivolumab concentrations [ Time Frame: Approximately 2-8 months ]
Trough (pre-dose) serum nivolumab concentrations will be measured using validated ELISA methods.
|Anticipated Study Start Date:||July 2017|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
|Experimental: TRC105 plus Nivolumab||Drug: Carotuximab
Anti Endoglin Antibody
Other Name: TRC105
Programmed Death Receptor-1
Other Name: Nivolumab
|Ages Eligible for Study:||18 Years and older (Adult, Senior)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Histologically confirmed metastatic non-small cell lung cancer (NSCLC) with disease recurrence or progression during or after prior platinum-containing doublet chemotherapy regimen
- Patients with an active oncogenic driver (e.g., epidermal growth factor [EGFR], activin-receptor-like kinase 1 [ALK1], or the proto-oncogene tyrosine-protein kinase ROS-1) must have progressed on or after a US Food and Drug Administration (FDA)- approved therapy for that aberration (Note: Previous treatment with a tyrosine kinase inhibitor and platinum-based doublets does not exclude the patient.).
- Patients who received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and developed recurrent or metastatic disease within 6 months of completing therapy are not excluded.
- Patients with recurrent disease > 6 months after adjuvant or neoadjuvant platinum- based chemotherapy, who also subsequently progressed during or after a platinum- doublet regimen given to treat the recurrence, are not excluded.
- Formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival) – Biopsy should be excisional, incisional, or core. Needle aspiration is insufficient.
- Programmed death ligand 1 (PD-L1) expression on ≥ 1% of tumor cells by validated immunohistochemistry assay
- Measurable disease by irRECIST
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Resolution of all acute adverse events resulting from prior cancer therapies to National Cancer Institute (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 glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 times upper limit of normal (ULN) or ≤ 5 times ULN in cases of liver metastases
- Total serum bilirubin ≤ 1.5 times the ULN
- Absolute neutrophil count (ANC) ≥ 1500/μL
- Platelets ≥ 100,000/μL without transfusion support within 28 days prior to study treatment
- Hemoglobin ≥ 9.0 g/dL without transfusion support within 14 days prior to study treatment (erythropoietin or darbepoetin permitted)
- Serum creatinine ≤ 1.5 times the ULN 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
- Autoimmune disease (Note: Vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, and conditions not expected to recur in the absence of an external trigger are permitted.)
- Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to study treatment (Note: Inhaled and topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.)
- History or active interstitial lung disease
- Immunosuppression, of any kind
- Prior therapy with T-cell therapy, including an immune checkpoint inhibitor
- Prior treatment with carotuximab
- Current treatment on another therapeutic clinical trial
- Receipt of systemic anticancer therapy, including investigational agents, within 28 days prior to study treatment (Note: If anticancer therapy was given within 28 days prior to starting study treatment, patients are not excluded if ≥ 5 times the elimination half-life of the drug has elapsed.)
- Major surgical procedure or significant traumatic injury within 4 weeks prior to study treatment, and must have fully recovered from any such procedure; and no date of surgery (if applicable) or anticipated need for a major surgical procedure planned within the next 6 months (Note: The following are not considered to be major procedures and are permitted up to 7 days prior to study treatment: 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.)
- Prior chest radiotherapy ≤ 3 months, 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 treatment – Such patients must have recovered adequately from any side effects of such therapy.
- Hypertension defined as blood pressure (BP) systolic > 150 or diastolic > 90 mm Hg (Note: Initiation or adjustment of antihypertensive medication prior to study entry is allowed provided that the average of 3 BP readings prior to study treatment is ≤150/90 mm Hg.)
- Ascites or pericardial effusion that required intervention within 3 months prior to study treatment
- History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease (Note: 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 over the 14 days prior to study treatment)
- Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment
- Deep venous thrombosis within 6 months prior to study treatment, unless the patient is anti-coagulated without the use of warfarin for ≥2 weeks prior to study treatment; 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)
- Thrombolytic use (except to maintain IV catheters) within 10 days prior study treatment
- Known active viral or nonviral hepatitis or cirrhosis
- Any active infection requiring systemic treatment
- History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months prior to study treatment
- History of peptic ulcer within the past 3 months prior to study treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days prior to study treatment
- History of gastrointestinal perforation or fistula in the 6 months prior to study treatment, 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., ≥6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of carotuximab. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to study treatment. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of carotuximab. The definition of effective contraception is provided in Section 2.6.1 of this protocol.
- 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
No Contacts or Locations Provided
|Responsible Party:||Tracon Pharmaceuticals Inc.|
|ClinicalTrials.gov Identifier:||NCT03181308 History of Changes|
|Other Study ID Numbers:||105LC102|
|Study First Received:||June 1, 2017|
|Last Updated:||June 6, 2017|
|Individual Participant Data|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Additional relevant MeSH terms:
|Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Physiological Effects of Drugs
ClinicalTrials.gov processed this record on June 08, 2017