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

Sponsor

NewLink Genetics Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT02187302

Collaborator

(none)

115

Enrollment

Locations

Arms

30.1

Duration (Months)

2.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: CRLX101 Drug: Bevacizumab Drug: Standard of Care (Investigator Choice)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

115 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CRLX101 + bevacizumab 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 Other Names: NLG207 Drug: Bevacizumab Other Names: Avastin
Active Comparator: Standard of Care 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) Other Names: sorafenib (Nexavar), sunitinib (Sutent), axitinib (Inlyta), pazopanib (Votrient), bevacizumab (Avastin), everolimus (Afinitor), Other

Arm

Intervention/Treatment

Experimental: CRLX101 + bevacizumab

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

Other Names:

NLG207

Drug: Bevacizumab

Other Names:

Avastin

Active Comparator: Standard of Care

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)

Other Names:

sorafenib (Nexavar), sunitinib (Sutent), axitinib (Inlyta), pazopanib (Votrient), bevacizumab (Avastin),

everolimus (Afinitor), Other

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [at least 6 months]
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) [at least 30 days post last dose of study drug]
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 [on average 12 months after discontinuation of study treatment]
To compare time to death between treatment groups of CRLX101 in combination with bevacizumab compared to SOC.
Objective response rate [at least 6 months]
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 [at least 6 months]
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 [at least 6 months]
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 [at least 6 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego	La Jolla	California	United States	92093
2	David Geffen School of Medicine UCLA	Los Angeles	California	United States	90024
3	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
4	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
5	Emory University	Atlanta	Georgia	United States	30322
6	Kaiser Permanente	Honolulu	Hawaii	United States	96819
7	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
8	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
9	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
10	June E. Nylen Cancer Center	Sioux City	Iowa	United States	51101
11	The University of Kansas Cancer Center	Fairway	Kansas	United States	66205
12	Cancer Center of Kansas	Wichita	Kansas	United States	67214
13	Our Lady of the Lake Physician Group	Baton Rouge	Louisiana	United States	70808
14	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
15	Ann Arbor Hematoloty-Oncology	Ann Arbor	Michigan	United States	48106
16	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
17	North Mississippi Hematology and Oncology Associates	Tupelo	Mississippi	United States	38801
18	University of Nebraska Medical Center	Omaha	Nebraska	United States	68130
19	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
20	MD Anderson Cooper Cancer Institute	Voorhees	New Jersey	United States	08043
21	New York Oncology Hematology	Albany	New York	United States	12208
22	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
23	SUNY Upstate Medical University	Syracuse	New York	United States	13210
24	UNC Chapel Hill	Chapel Hill	North Carolina	United States	27599
25	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
26	University of Pittsburgh Medical Center Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
27	Cancer Centers of the Carolinas	Greenville	South Carolina	United States	29615
28	Texas Oncology, Amarillo	Amarillo	Texas	United States	79106
29	Texas Oncology P.A.	Austin	Texas	United States	78745
30	Texas Oncology, Dallas	Dallas	Texas	United States	75246
31	Texas Oncology, El Paso	El Paso	Texas	United States	79902
32	Texas Oncology, Flower Mound	Flower Mound	Texas	United States	75028
33	Texas Oncology, Fort Worth	Fort Worth	Texas	United States	76104
34	Texas Oncology, P.A.	Houston	Texas	United States	77024
35	Cancer Center Network of South Texas	San Antonio	Texas	United States	78217
36	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
37	CAMC Health Education and Research Institute	Charleston	West Virginia	United States	25304
38	St. Vincent Regional Cancer Center CCOP	Green Bay	Wisconsin	United States	54301
39	National Cancer Center	Goyang-si Gyeonggi-do		Korea, Republic of	410-769
40	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
41	Severence Hospital	Seoul		Korea, Republic of	120-752
42	Samsung Medical Center	Seoul		Korea, Republic of	135-710
43	Asan Medical Center	Seoul		Korea, Republic of	138-736