Overview

This trial is active, not recruiting.

Condition metastatic renal cell carcinoma
Treatments crlx101 + bevacizumab, sorafenib / everolimus / pazopanib / axitinib / bevacizumab / sunitinib / other approved drug
Phase phase 2
Targets VEGF, RAF, PDGF, mTOR, FLT-3, KIT, FKBP-12
Sponsor Cerulean Pharma Inc.
Start date July 2014
End date January 2016
Trial size 110 participants
Trial identifier NCT02187302, CRLX101-208

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
crlx101 + bevacizumab
(Active Comparator)
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
sorafenib / everolimus / pazopanib / axitinib / bevacizumab / sunitinib / other approved drug sorafenib (Nexavar), sunitinib (Sutent), axitinib (Inlyta), pazopanib (Votrient), bevacizumab (Avastin),

Primary Outcomes

Measure
Progression free survival
time frame: at least 6 months

Secondary Outcomes

Measure
Number of serious and non-serious adverse events
time frame: at least 30 days post last dose of study drug
Overall survival
time frame: on average 12 months after discontinuation of study treatment
Objective response rate
time frame: at least 6 months
Pharmacokinetic measures of CRLX101 in plasma
time frame: on days 1 (pre-infusion, end of infusion, 1,2,4 and 6 hrs post infusion), 2, 3, 8 and 15 of cycle 1 (month 1) and repeat in cycle 3 (month 3)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title 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)
Description Open-label, randomized, controlled study in patients with metastatic RCC (mRCC) who have completed 2 or 3 prior conventional molecularly targeted therapy regimens (i.e. lines) including ≥ 1 VEGF-inhibiting therapies. A total of 110 patients with 55 per treatment arm will be recruited from up to 40 clinical sites. Subjects will be randomized to either CRLX101 in combination with bevacizumab (CRLX101 15 mg/m^2 IV on days 1 and 15 of a 28-day cycle; in combination with bevacizumab 10 mg/kg IV on days 1 and 15 of 28-day cycle) or standard of care (SOC). Options for SOC treatment include 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. Measurable disease will be assessed every 8 weeks (i.e. every 2 cycles). Study treatment, for both investigational and reference therapy, will continue until confirmed disease progression. Duration of study treatment on average is expected to be up to 6 months. Other reasons for discontinuation of treatment may include Investigator determination of clinical progression without CT-Scan confirmation, patient withdrawal, unresolved adverse event, unacceptable toxicity, Investigator decision in consultation with the patient, death, Sponsor determination due to protocol violation, or Sponsor decision to close the study. Cross-over treatment will not be permitted on-study for either assigned treatment arm. Bevacizumab has been chosen as a combination partner with CRLX101 for a number of reasons. - Bevacizumab has proven activity in the treatment of patients with renal cell carcinoma. - Bevacizumab has been successfully combined with many chemotherapy partners including the topoisomerase-1 inhibitor irinotecan. - It has been hypothesized that the combination of bevacizumab with CRLX101 may have unique clinical activity in combination in the treatment of this disease due to the simultaneous inhibition of distinct steps along the ~vHL ┐ HIF → (CAIX) → VEGF → VEGFR2 pathway Primary Objective: To assess progression free survival (PFS) in patients with metastatic renal cell carcinoma (mRCC) treated with CRLX101 in combination with bevacizumab (CRLX101+bevacizumab) vs. standard of care (SOC) per investigator's choice. This primary endpoint will be evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Secondary Objectives - To assess overall safety and tolerability of CRLX101+ bevacizumab compared to SOC. - To assess overall survival (OS) of CRLX101+bevacizumab compared to SOC. - To assess overall response rate (ORR) of CRLX101+bevacizumab compared to SOC. - To assess overall PFS, OS, and ORR among patients with clear cell RCC treated with CRLX101+bevacizumab compared to SOC. - To assess overall PFS, OS, and ORR among patients with non-clear cell RCC treated with CRLX101+bevacizumab compared to SOC. - To describe the pharmacokinetics (PK) of CRLX101 when administered in combination with bevacizumab. Exploratory Objectives - To analyze tumor tissue samples for biomarkers of efficacy in the CRLX101+bevacizumab treatment group. - To analyze plasma samples for biomarkers of efficacy before and during treatment and correlate with efficacy outcomes for CRLX101+bevacizumab compared to SOC treatment groups. - To evaluate the pharmacokinetics (PK) of CRLX101 in urine over time when administered in combination with bevacizumab in patients with and without non-infective cystitis.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Cerulean Pharma Inc..
Location data was received from the National Cancer Institute and was last updated in March 2016.