Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02219711

Collaborator

(none)

260

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles.

During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations.

Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer	Drug: MGCD516	Phase 1

Detailed Description

During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.

During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon the following cancer diagnosis:

Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL.

Head and neck squamous cell carcinoma with genetic alterations in MET.

Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.

Metastatic prostate cancer with bone metastases.

Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies

Study Start Date :

Aug 1, 2014

Anticipated Primary Completion Date :

Aug 1, 2020

Anticipated Study Completion Date :

Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MGCD516 MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles	Drug: MGCD516 MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water. Other Names: Sitravatinib

Arm

Intervention/Treatment

Experimental: MGCD516

MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles

Drug: MGCD516

MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.

Other Names:

Sitravatinib

Outcome Measures

Primary Outcome Measures

Type of dose limiting adverse event [Up to 3 weeks on treatment]
Area under the plasma concentration versus time curve (AUC) of MGCD516 [Up to 72 hours]
Peak Plasma Concentration (Cmax) of MGCD516 [Up to 72 hours]

Secondary Outcome Measures

Kind of metabolites of MGCD516 in blood plasma [Up to 9 weeks on treatment]
Concentration of selected marker proteins in blood plasma [Up to 9 weeks on treatment]
Proteins include VEGF A, soluble VEGF-R2 and soluble MET
Percent of patients having objective disease response to treatment [Up to 1 year on treatment]
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Metastatic or unresectable solid tumor malignancy
Standard treatment is not available
Adequate bone marrow and organ function

Exclusion Criteria:

History of a significant cardiovascular illness
Prolonged corrected QT (QTc) interval
Left ventricular ejection fraction < 40%
Symptomatic or uncontrolled brain metastases
Other active cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	University of California, San Diego	San Diego	California	United States	92093
3	University of California, San Francisco	San Francisco	California	United States	94143
4	Sarcoma Oncology Research Center	Santa Monica	California	United States	90403
5	Innovative Clinical Research Institute	Whittier	California	United States	90602
6	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
7	Holy Cross Michael & Dianne Bienes Comprehensive Cancer Center	Fort Lauderdale	Florida	United States	33308
8	Florida Cancer Affiliates	Ocala	Florida	United States	34471
9	Florida Cancer Specialists	Sarasota	Florida	United States	34232
10	Northwestern University	Chicago	Illinois	United States	60611
11	Rush University Medical Center	Chicago	Illinois	United States	60612
12	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
13	Maryland Oncology Hematology,	Rockville	Maryland	United States	20850
14	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
15	University of Michigan	Ann Arbor	Michigan	United States	48109
16	Henry Ford Health System	Detroit	Michigan	United States	48202
17	Washington University Center for Advanced Medicine	Saint Louis	Missouri	United States	63110
18	CHI Health St Francis, Saint Francis Cancer Treatment Center	Grand Island	Nebraska	United States	68803
19	Oncology Hematology West PC, Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
20	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87102
21	Montefiore Medical Center	Bronx	New York	United States	10467
22	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
23	Columbia University	New York	New York	United States	10032
24	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45242
25	Guthrie Clinical Research	Sayre	Pennsylvania	United States	18840
26	St. Francis Cancer Center	Greenville	South Carolina	United States	29607
27	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
28	Texas Oncology-Austin Midtown	Austin	Texas	United States	78705
29	Mary Crowley Cancer Research Center	Dallas	Texas	United States	75251
30	University of Texas, MD Anderson Cancer Center	Houston	Texas	United States	77030
31	Texas Oncology-Tyler	Tyler	Texas	United States	75702
32	The Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
33	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
34	Oncology and Hematology Associates of Southwest Virginia, Inc., Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
35	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
36	Northwest Cancer Specialists, P.C.	Vancouver	Washington	United States	98684
37	University of Wisconsin	Madison	Wisconsin	United States	53792
38	Chungbuk National University Hospital	Cheongju-si		Korea, Republic of
39	Keimyung University Dongsan Hospital	Daegu		Korea, Republic of
40	National Cancer Center	Goyang-si		Korea, Republic of
41	Korea Veterans Health Service	Seoul		Korea, Republic of
42	Seoul National University Hospital	Seoul		Korea, Republic of
43	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of