Randomized Phase 2 Trial of Axitinib and TRC105 Versus Axitinib Alone in Patients Renal Cell Carcinoma
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|ClinicalTrials.gov Identifier: NCT01806064|
Recruitment Status : Terminated (The study did not meet endpoint.)
First Posted : March 7, 2013
Results First Posted : October 19, 2020
Last Update Posted : October 19, 2020
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Phase 1b: To evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose axitinib in patients with advanced renal cell carcinoma.
Phase 2: To estimate the PFS of patients with advanced or metastatic RCC by RECIST 1.1 criteria in patients treated with axitinib and TRC105 compared to those treated with axitinib alone, following failure of one prior VEGF TKI
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma||Drug: TRC105 and Axitinib Drug: Axitinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||173 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||March 8, 2013|
|Actual Primary Completion Date :||December 21, 2018|
|Actual Study Completion Date :||June 12, 2019|
Experimental: TRC105 and Axitinib
Patients randomized to receive TRC105 at 3 mg/kg on day 1, 7 mg/kg on day 4, and 10 mg/kg on day 8 and weekly thereafter in combination with axitinib 5 mg twice daily
Drug: TRC105 and Axitinib
Active Comparator: Axitinib
Patients randomized to receive axitinib 5 mg twice daily
Other Name: Inlyta
- Phase 1b: Number of Patients With DLT [ Time Frame: 12 Months ]Phase 1b: For dose limiting toxicity (DLT) evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0).
- Phase 2: Progression Free Survival (PFS) of Patients With RCC [ Time Frame: 15 Months ]Median progression free survival (PFS) of patients with advanced or metastatic RCC by RECIST 1.1. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Phase 1b & 2: Response Rate of Patients With RCC [ Time Frame: 15 Months ]Number of patients with partial response (PR) or complete response (CR) by RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Phase 2: Overall Response Rate of Patients With RCC by Choi [ Time Frame: 15 Months ]Overall response (OR) rate is the number of patients with partial response (PR) or complete response (CR) by Choi Criteria. Per Choi criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), A decrease in size ≥ 10% or a decrease in tumor attenuation (Houndsfield units) ≥ 15% on CT and no new lesions; Overall Response (OR) = CR + PR.
- Phase 1b & 2: Trough Concentrations of TRC105 by Dose Level in Phase 1b [ Time Frame: 2.5 months (cycle 2 day 15) ]Trough Serum TRC105 concentrations at steady state (cycle 2 day 15) were measured using validated ELISA methods.
- Phase 1b & 2: Number of Patients With Development of Immunogenicity Antibodies. [ Time Frame: 12 months ]Anti-product antibody concentration were measured using validated ELISA methods.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Histologically confirmed advanced or metastatic renal cell carcinoma with a clear cell component that has progressed by investigator assessment following 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). One prior immunotherapy (interleukin-2 or interferon-alpha or immune checkpoint inhibitor or tumor vaccine) and one prior mTOR inhibitor treatment are allowed.
- 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.
- Measurable disease by RECIST 1.1 criteria
- Age of 18 years or older
- ECOG performance status ≤ 1
- Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia)
- Adequate organ function as defined by the following criteria:
- 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
- Prior treatment with TRC105 or axitinib or any agent targeting the endoglin pathway (including a fusion protein that binds bone morphogenic protein)
- Grade 3 or 4 toxicity related to prior VEGFR TKI that did not resolve to grade 1
- 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 or receipt of a biologic anticancer agent (e.g., antibody) within 28 days of starting study treatment.
- 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
- 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, thorascopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures
- 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)
- 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, 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.
- Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia).
- Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
- 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 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
- 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
- Requirement for concomitant medications that strongly induce or inhibit CYP3A4/5
- 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. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate.
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01806064
|Study Director:||Charles Theuer, MD PhDfirstname.lastname@example.org|
Documents provided by Tracon Pharmaceuticals Inc.:
|Responsible Party:||Tracon Pharmaceuticals Inc.|
|Other Study ID Numbers:||
|First Posted:||March 7, 2013 Key Record Dates|
|Results First Posted:||October 19, 2020|
|Last Update Posted:||October 19, 2020|
|Last Verified:||October 2020|
Renal Cell Carcinoma
Advanced Renal Cell Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action