Back to resultsCRLX101(NLG207) in Combination With Bevacizumab for Metastatic Renal Cell Carcinoma (mRCC) Versus Standard of Care (SOC)
Primary Purpose
Metastatic Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CRLX101
Bevacizumab
Standard of Care (Investigator Choice)
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Renal Cell Carcinoma focused on measuring nanopharmaceutical,
Eligibility Criteria
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
Sites / Locations
- University of California San Diego
- David Geffen School of Medicine UCLA
- Cedars Sinai Medical Center
- Rocky Mountain Cancer Centers
- Emory University
- Kaiser Permanente
- Decatur Memorial Hospital
- Indiana University School of Medicine
- Franciscan St. Francis Health
- June E. Nylen Cancer Center
- The University of Kansas Cancer Center
- Cancer Center of Kansas
- Our Lady of the Lake Physician Group
- University of Maryland, Greenebaum Cancer Center
- Ann Arbor Hematoloty-Oncology
- Karmanos Cancer Institute
- North Mississippi Hematology and Oncology Associates
- University of Nebraska Medical Center
- Comprehensive Cancer Centers of Nevada
- MD Anderson Cooper Cancer Institute
- New York Oncology Hematology
- Memorial Sloan Kettering Cancer Center
- SUNY Upstate Medical University
- UNC Chapel Hill
- University of Pennsylvania
- University of Pittsburgh Medical Center Cancer Institute
- Cancer Centers of the Carolinas
- Texas Oncology, Amarillo
- Texas Oncology P.A.
- Texas Oncology, Dallas
- Texas Oncology, El Paso
- Texas Oncology, Flower Mound
- Texas Oncology, Fort Worth
- Texas Oncology, P.A.
- Cancer Center Network of South Texas
- Utah Cancer Specialists
- CAMC Health Education and Research Institute
- St. Vincent Regional Cancer Center CCOP
- National Cancer Center
- Seoul National University Hospital
- Severence Hospital
- Samsung Medical Center
- Asan Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
CRLX101 + bevacizumab
Standard of Care
Arm Description
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.
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
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
Overall survival
To compare time to death between treatment groups of CRLX101 in combination with bevacizumab compared to SOC.
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
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
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
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
Full Information
NCT ID
NCT02187302
First Posted
June 30, 2014
Last Updated
May 26, 2020
Sponsor
NewLink Genetics Corporation
1. Study Identification
Unique Protocol Identification Number
NCT02187302
Brief Title
CRLX101(NLG207) in Combination With Bevacizumab for Metastatic Renal Cell Carcinoma (mRCC) Versus Standard of Care (SOC)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NewLink Genetics Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
Keywords
nanopharmaceutical,
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
115 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CRLX101 + bevacizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
CRLX101
Other Intervention Name(s)
NLG207
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Type
Drug
Intervention Name(s)
Standard of Care (Investigator Choice)
Other Intervention Name(s)
sorafenib (Nexavar), sunitinib (Sutent), axitinib (Inlyta), pazopanib (Votrient), bevacizumab (Avastin),, everolimus (Afinitor), Other
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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
Time Frame
at least 6 months
Secondary Outcome Measure Information:
Title
Overall Safety and tolerability (AEs, SAEs, Clinical Laboratory Parameters, Vital Signs, Concomitant Medications)
Description
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.
Time Frame
at least 30 days post last dose of study drug
Title
Overall survival
Description
To compare time to death between treatment groups of CRLX101 in combination with bevacizumab compared to SOC.
Time Frame
on average 12 months after discontinuation of study treatment
Title
Objective response rate
Description
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
Time Frame
at least 6 months
Title
Duration of Response
Description
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
Time Frame
at least 6 months
Title
PFS
Description
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
Time Frame
at least 6 months
Title
PFS
Description
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
Time Frame
at least 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
NewLink Genetics
Organizational Affiliation
NewLink Genetics Inc
Official's Role
Study Chair
Facility Information:
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
David Geffen School of Medicine UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
Cedars Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Kaiser Permanente
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96819
Country
United States
Facility Name
Decatur Memorial Hospital
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Franciscan St. Francis Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
June E. Nylen Cancer Center
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101
Country
United States
Facility Name
The University of Kansas Cancer Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Our Lady of the Lake Physician Group
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
University of Maryland, Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Ann Arbor Hematoloty-Oncology
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
North Mississippi Hematology and Oncology Associates
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
MD Anderson Cooper Cancer Institute
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
Facility Name
New York Oncology Hematology
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
UNC Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Medical Center Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Cancer Centers of the Carolinas
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Texas Oncology, Amarillo
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79106
Country
United States
Facility Name
Texas Oncology P.A.
City
Austin
State/Province
Texas
ZIP/Postal Code
78745
Country
United States
Facility Name
Texas Oncology, Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Texas Oncology, El Paso
City
El Paso
State/Province
Texas
ZIP/Postal Code
79902
Country
United States
Facility Name
Texas Oncology, Flower Mound
City
Flower Mound
State/Province
Texas
ZIP/Postal Code
75028
Country
United States
Facility Name
Texas Oncology, Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Oncology, P.A.
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
Cancer Center Network of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
CAMC Health Education and Research Institute
City
Charleston
State/Province
West Virginia
ZIP/Postal Code
25304
Country
United States
Facility Name
St. Vincent Regional Cancer Center CCOP
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
Facility Name
National Cancer Center
City
Goyang-si Gyeonggi-do
ZIP/Postal Code
410-769
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Severence Hospital
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
28950297
Citation
Voss MH, Hussain A, Vogelzang N, Lee JL, Keam B, Rha SY, Vaishampayan U, Harris WB, Richey S, Randall JM, Shaffer D, Cohn A, Crowell T, Li J, Senderowicz A, Stone E, Figlin R, Motzer RJ, Haas NB, Hutson T. A randomized phase II trial of CRLX101 in combination with bevacizumab versus standard of care in patients with advanced renal cell carcinoma. Ann Oncol. 2017 Nov 1;28(11):2754-2760. doi: 10.1093/annonc/mdx493.
Results Reference
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CRLX101(NLG207) in Combination With Bevacizumab for Metastatic Renal Cell Carcinoma (mRCC) Versus Standard of Care (SOC)
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