CRLX101(NLG207) in Combination With Bevacizumab for Metastatic Renal Cell Carcinoma (mRCC) Versus Standard of Care (SOC)

Study Overview
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Brief Summary
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This study to evaluate treatment in patients with metastatic renal cell carcinoma (RCC) which has progressed through 2 to 3 prior lines of therapy, with the investigational drug CRLX101 in combination with bevacizumab compared to treatment with a standard of care therapy. The study will compare which treatment resulted in longer time before progression of the RCC. Patients will be treated and followed for progression of their disease on average for up to 6 months.

Official Title
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A Randomized, Phase 2 Study to Assess the Safety and Efficacy of CRLX101 in Combination With Bevacizumab in Patients With Metastatic Renal Cell Carcinoma (RCC) Versus Standard of Care (SOC) (Investigator's Choice)

Conditions
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Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Drug: CRLX101
* Drug: Bevacizumab
* Drug: Standard of Care (Investigator Choice)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have histologically confirmed renal cell carcinoma of any pathologic subtype. Must have unresectable metastatic disease, and have tumor(s) present that is (are) evaluable by the RECIST, v1.1; may have spinal-associated metastases but must have concluded dexamethasone therapy and be evaluated by the Investigator to have stable CNS disease. Must have received 2 or 3 prior lines of conventional molecularly targeted therapy Must have full recovery from any toxicities from prior therapy CTCAE Grade 1 or less with the exception of Grade 2 alopecia) prior to randomization. ECOG performance status 0 or 1. Age 18 years and older. Life expectancy of at least 3 months. Must have normal organ and marrow function reported within 14 days prior to randomization Ability to understand and willingness to sign a written informed consent document. Able to comply with study visit schedule and assessments. Exclusion Criteria: Any conventional molecularly targeted therapy within 2 weeks or, chemotherapy or radiotherapy within 2 weeks (local) or 4 weeks (systemic) prior to entering the study. Failure to recover to grade 1 or less all prior adverse events. Any major surgery within 4 weeks of study randomization. Any prior treatment with topoisomerase I therapy. Prior treatment with any drugs or therapies that will be administered during the course of this trial including CRLX101, any topoisomerase 1 inhibitor, bevacizumab or the conventional molecularly targeted agent intended for use as standard of care treatment. Patients receiving any other current investigational therapeutic agent. Other active malignancies Patients with brain metastasis treated or untreated, or other CNS disease Any clinically significant cardiac disease defined as NYHA class III or IV. Uncontrolled hypertension Uncontrolled concurrent illness History of non-healing wounds or ulcers. Pregnancy, or inadequate contraception for men or women of childbearing age, or lactating / breast-feeding Patients with known HIV or with solid organ transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRLX101 + bevacizumab<br>CRLX101 in combination with bevacizumab: CRLX101 15 mg/m^2 IV on days 1 and 15 of a 28-day cycle; bevacizumab 10 mg/kg IV on days 1 and 15 of a 28-day cycle. | Drug: CRLX101<br> <br> * Other names: NLG207;Drug: Bevacizumab<br> <br> * Other names: Avastin;|
| Active Comparator: Standard of Care<br>Standard of care treatment include one of the following agents to which the patient can have no prior exposure: sorafenib; everolimus; pazopanib; axitinib; bevacizumab; sunitinib, or other approved drug considered by the Medical Monitor to represent an acceptable standard of care therapy | Drug: Standard of Care (Investigator Choice)<br> <br> * Other names: everolimus (Afinitor), Other;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | To assess progression free survival (PFS) in patients with clear cell metastatic renal cell carcinoma (RCC) treated with CRLX101 in combination with bevacizumab (CRLX101+bevacizumab) vs. standard of care (SOC) per investigator's choice, as assessed by blinded independent radiological review (IRR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | at least 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Safety and tolerability (AEs, SAEs, Clinical Laboratory Parameters, Vital Signs, Concomitant Medications) | AEs will be coded using MedDRA and graded according to CTCAE (v 4.03). The number and percentage of patients with any treatment-emergent AE (TEAE) will be summarized for each treatment group. The number of patients with TEAEs assessed by the Investigator as at least possibly related to treatment will be tabulated. The number of patients with any CTCAE grade ≥ 3 treatment-emergent AE will be tabulated. Serious AEs (SAEs) will also be tabulated. For Clinical Laboratory Parameters - Shift tables that present changes from baseline to worst on-study values relative to CTCAE grading will be produced. For Vital Signs - By-patient data listings of vital sign measurements will be presented. For Concomitant Medications - The use of concomitant medications will be included in by-patient data listings. A summary table of concomitant medications by WHO drug class will also be provided. | at least 30 days post last dose of study drug | 
| Overall survival | To compare time to death between treatment groups of CRLX101 in combination with bevacizumab compared to SOC. | on average 12 months after discontinuation of study treatment | 
| Objective response rate | Evaluate response rates comparing the investigational treatment of CRLX101 in combination with bevacizumab compared to SOC as assessed by blinded IRR as well as by the Investigator | at least 6 months | 
| Duration of Response | Evaluate time to response comparing the investigational treatment of CRLX101 in combination with bevacizumab compared to SOC as assessed by blinded IRR as well as by the Investigator | at least 6 months | 
| PFS | To assess PFS in patients with clear cell metastatic RCC treated with CRLX101+bevacizumab vs. SOC per investigator's choice, as assessed at the site level by the Investigator according to RECIST version 1.1 | at least 6 months | 
| PFS | To assess PFS (as assessed at the site level by the Investigator and separately by blinded IRR) in clear cell RCC patients treated with CRLX101+bevacizumab compared to bevacizumab treatment alone | at least 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nanopharmaceutical,