A RANDOMIZED PHASE 2 TRIAL OF AXITINIB AND TRC105 VERSUS AXITINIB ALONE (INCLUDING A LEAD-IN PHASE 1B DOSE-ESCALATION PORTION) IN PATIENTS WITH ADVANCED OR METASTATIC RENAL CELL CARCINOMA
- Conditions
- ADVANCED OR METASTATIC RENAL CELL CARCINOMAMedDRA version: 20.0Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003436-13-HU
- Lead Sponsor
- TRACON Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 173
1.PHASE 2 ONLY: Histologically confirmed advanced or metastatic renal cell carcinoma with a clear cell component that has progressed by investigator assessment on treatment with one and only one multi-targeted tyrosine kinase inhibitor (TKI) other than axitinib that targets the VEGF receptor (VEGFR) (e.g., sunitinib, pazopanib, sorafenib, tivozanib, cabozantinib) OR bevacizumab. Patients who received VEGF inhibitor treatment for = one month due to documented intolerance in the absence of progression, and were started on a second VEGF inhibitor within one month of discontinuing the initial VEGF inhibitor are eligible. One prior immunotherapy (interleukin-2 or interferon-alpha or immune checkpoint inhibitor or tumor vaccine) and one prior mTOR inhibitor treatment are allowed. Prior adjuvant therapy is permitted in the absence of disease progression during treatment, but no further VEGF treatment is allowed if progression occurred on adjuvant VEGF inhibitor treatment.
2. PHASE 1B COHORT 3 AND 4 ONLY: Histologically confirmed advanced or metastatic renal cell carcinoma that has progressed by investigator assessment on treatment with at least TWO VEGF inhibitors (e.g., sunitinib, pazopanib, sorafenib, tivozanib, cabozantinib, bevacizumab). Prior immunotherapy (interleukin-2 or interferon-alpha or immune checkpoint inhibitor or tumor vaccine), or mTOR inhibitor treatment is allowed.
3.No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission per investigators' clinical judgment.
4.Measurable disease by RECIST 1.1 criteria
5.Age of 18 years or older
6.ECOG performance status = 1
8.Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade = 1 or baseline (except alopecia)
9.Adequate organ function as defined by the following criteria:
•AST and ALT = 2.5 x 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 14 days (erythropoietin or darbepoetin permitted)
•Serum creatinine = 1.5 times the upper limit of normal or creatinine clearance > 30 mL/min by Cockcroft-Gault formula
•INR between 0.8 – 1.2
9.Willingness and ability to consent for self to participate in study
10.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
11.Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use condom with spermecid and to not donate sperm and for at least 180 days following last dose of TRC105 or axitinib.
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 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 two acceptable methods of birth control,one of which must be highly effective during the study and for at least 180 days after stopping TRC
1.PHASE 2: Prior treatment with TRC105 or axitinib or any agent targeting the endoglin pathway (including a fusion protein that binds bone morphogenic protein)
2.PHASE 1B COHORT 3 & 4 ONLY: Prior treatment with TRC105
3.Grade 3 or 4 toxicity related to prior VEGF inhibitor that did not resolve to grade 1
4.Current treatment on another therapeutic clinical trial
5.Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment. If anticancer therapy was given within 28 days of starting study treatment, patients may be included if 5 times the elimination half-life of the drug passed.
6.Prior radiation therapy within 28 days of starting the study treatment, except radiation therapy for bone metastases or radiosurgery is permitted up to 14 days of starting treatment
7.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). Note: the following are not considered to be major procedures and are permitted up to 7 days before therapy initiation: Thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures
8.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 < 150/90 mm Hg)
9.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.
10.Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or 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.
11.Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia).
12.Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
13.Known active viral or nonviral hepatitis or cirrhosis
14.History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment
15.History of peptic ulcer disease within 3 months of treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
16.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)
17.Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
18.Receipt of a strong CYP3A4/5 inducer within 12 days prior to cycle 1 day 1 or a strong CYP3A4/5 inhibitor within 7 days pri
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