Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01688973
• Collaborator: (none)
• Enrollment: 55
• Locations: 214
• Arms: 2
• Duration (Months): 56.3
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Renal Cell Carcinoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma	Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Tivantinib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the response rate (confirmed complete and partial response) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 (tivantinib) or ARQ 197 combined with erlotinib (erlotinib hydrochloride).

SECONDARY OBJECTIVES:

1. To assess the progression free survival (PFS) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 or ARQ 197 combined with erlotinib.

2. To assess the safety and tolerability of ARQ 197 therapy and ARQ 197 combined with erlotinib.

3. To descriptively assess the role of prior treatment on outcome.

TERTIARY OBJECTIVES:

1. To bank tissue specimens for future use and once funding is obtained to evaluate the expression of tissue correlative biomarkers such as hepatocyte growth factor receptor (c-MET) and epidermal growth factor receptor (EGFR), and to perform exploratory correlation with clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28.

ARM II: Patients receive tivantinib PO BID and erlotinib hydrochloride PO once daily (QD) on days 1-28.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Parallel (Randomized) Phase II Evaluation of ARQ 197 and ARQ 197 in Combination With Erlotinib in Papillary Renal Cell Carcinoma
• Study Start Date: Aug 20, 2012
• Actual Primary Completion Date: Apr 30, 2017
• Actual Study Completion Date: Apr 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (tivantinib) Patients receive tivantinib PO BID on days 1-28.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Tivantinib; 360 mg (3 tablets) by mouth, Twice daily (720 mg total daily dose) on days 1-28, until disease progression
Experimental: Arm II (tivantinib and erlotinib hydrochloride) Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28.	Drug: Erlotinib Hydrochloride; 150 mg (1 tablet) by mouth on days 1-28, once daily, until disease progression; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Tivantinib; 360 mg (3 tablets) by mouth, Twice daily (720 mg total daily dose) on days 1-28, until disease progression

Outcome Measures

Primary Outcome Measures

1. Response Rate (Confirmed Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors [Up to 3 years]

   Best Response is calculated from the sequence of objective statuses. CR: Two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. PR: Two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration, but not qualifying as CR. Stable/no response: At least one objective status of stable/no response documented at least 6 weeks after registration and before progression or symptomatic deterioration, but not qualifying as anything else above. Increasing disease: Objective status of progression within 12 weeks of registration, not qualifying as anything else above. Symptomatic deterioration: Objective status of symptomatic deterioration within 12 weeks of registration, not qualifying as anything else above.

Secondary Outcome Measures

1. Frequency and Severity of Toxicities, Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 3 years]

   This study utilized the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 for toxicity and Serious Adverse Event reporting. Patients were evaluated every two weeks for the first eight weeks and then once every four weeks. If all protocol treatment is delayed more than three weeks, patients were removed from protocol treatment

2. Progression-free Survival (PFS) [30 months]

   From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact.

Other Outcome Measures

1. Number of Participants With c-MET Amplification, Deletion and No Alteration [Baseline]

2. Number of Participants With EGFR Amplification, Deletion and No Alteration [Baseline]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic, or locally advanced and unresectable; mixed histologies will be allowed provided that they contain >= 50% of the papillary component

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; x-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; x-rays, scans or physical examinations for non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment form

• Patients with metastatic disease who have a resectable primary tumor and are deemed a surgical candidate may have undergone resection; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery

• Patients with a history of brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)

• Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma; patients must not have received a MET inhibitor or erlotinib as prior therapy; at least 21 days must have elapsed since completion of prior systemic therapy, 42 days for nitrosoureas or mitomycin C; patients must have recovered from all associated toxicities at the time of registration

• Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 21 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration

• Patients must not be receiving or planning to receive any other investigational agents

• Patients must have a complete physical examination and medical history within 28 days prior to registration

• Patients must have a Zubrod performance status of 0-2

• White blood cell (WBC) >= 2,000/mcL

• Absolute neutrophil count (ANC) >= 1,000/mcL

• Platelet count >= 75,000/mcL

• Serum bilirubin =< 1.5 x institutional upper limits of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) must be =< 1.5 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT/SGPT) must be =< 5 x the institutional ULN

• Serum creatinine must be =< 2 x the institutional ULN

• Sodium, potassium and calcium must be obtained within 14 days prior to registration

• Patients with a known history of the following corneal diseases are not eligible: dry eye syndrome, Sjogren's syndrome, keratoconjunctivitis sicca, exposure keratopathy, Fuchs' dystrophy or other active disorders of cornea

• Patients known to be human immunodeficiency virus (HIV)-positive and receiving combination anti-retroviral therapy are not eligible

• Patients must be able to take oral medications; patients must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease; patients with intractable nausea or vomiting are not eligible

• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

• Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies

• All patients must be informed of the investigational nature of this study and must sign and give written informed consent

• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
2	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
3	The University of Arizona Medical Center-University Campus	Tucson	Arizona	United States	85724
4	Kaiser Permanente-Anaheim	Anaheim	California	United States	92807
5	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
6	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
7	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
8	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
9	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
10	Kaiser Permanente Hospital	Fontana	California	United States	92335
11	Kaiser Permanente - Harbor City	Harbor City	California	United States	90710
12	Kaiser Permanente-Irvine	Irvine	California	United States	92618
13	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
14	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
15	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
16	Kaiser Permanente-Cadillac	Los Angeles	California	United States	90034
17	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
18	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
19	Sutter Cancer Research Consortium	Novato	California	United States	94945
20	Stanford Cancer Institute	Palo Alto	California	United States	94304
21	Kaiser Permanente - Panorama City	Panorama City	California	United States	91402
22	Kaiser Permanente-Riverside	Riverside	California	United States	92505
23	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
24	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
25	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
26	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
27	Kaiser Permanente-San Marcos	San Marcos	California	United States	92069
28	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
29	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California	United States	96161
30	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
31	Kaiser Permanente	Woodland Hills	California	United States	91367
32	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
33	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
34	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
35	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
36	George Washington University Medical Center	Washington	District of Columbia	United States	20037
37	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
38	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
39	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
40	Northwestern University	Chicago	Illinois	United States	60611
41	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois	United States	60035
42	Hines Veterans Administration Hospital	Hines	Illinois	United States	60141
43	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
44	NorthShore Hematology Oncology-Libertyville	Libertyville	Illinois	United States	60048
45	Loyola University Medical Center	Maywood	Illinois	United States	60153
46	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
47	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
48	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
49	Franciscan Health Indianapolis	Indianapolis	Indiana	United States	46237
50	Reid Health	Richmond	Indiana	United States	47374
51	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
52	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
53	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
54	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
55	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
56	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
57	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
58	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
59	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas	United States	67530
60	Hays Medical Center	Hays	Kansas	United States	67601
61	Hutchinson Regional Medical Center	Hutchinson	Kansas	United States	67502
62	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
63	Providence Medical Center	Kansas City	Kansas	United States	66112
64	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
65	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
66	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
67	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
68	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
69	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
70	Menorah Medical Center	Overland Park	Kansas	United States	66209
71	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
72	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
73	Via Christi Hospital-Pittsburg	Pittsburg	Kansas	United States	66762
74	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
75	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
76	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
77	Salina Regional Health Center	Salina	Kansas	United States	67401
78	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas	United States	66606
79	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
80	Associates In Womens Health	Wichita	Kansas	United States	67208
81	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
82	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
83	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
84	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
85	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
86	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
87	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
88	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
89	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
90	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
91	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
92	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
93	Hurley Medical Center	Flint	Michigan	United States	48502
94	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
95	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
96	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
97	Allegiance Health	Jackson	Michigan	United States	49201
98	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
99	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
100	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
101	Sparrow Hospital	Lansing	Michigan	United States	48912
102	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
103	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
104	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
105	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
106	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
107	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
108	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
109	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
110	Unity Hospital	Fridley	Minnesota	United States	55432
111	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
112	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
113	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
114	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
115	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
116	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
117	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
118	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
119	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
120	Regions Hospital	Saint Paul	Minnesota	United States	55101
121	United Hospital	Saint Paul	Minnesota	United States	55102
122	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
123	Lakeview Hospital	Stillwater	Minnesota	United States	55082
124	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
125	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
126	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
127	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
128	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
129	Truman Medical Center	Kansas City	Missouri	United States	64108
130	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
131	North Kansas City Hospital	Kansas City	Missouri	United States	64116
132	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
133	Research Medical Center	Kansas City	Missouri	United States	64132
134	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
135	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
136	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
137	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
138	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
139	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
140	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
141	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
142	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
143	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
144	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey	United States	07018-1095
145	Glens Falls Hospital	Glens Falls	New York	United States	12801
146	Orange Regional Medical Center	Middletown	New York	United States	10940
147	Columbia University/Herbert Irving Cancer Center	New York	New York	United States	10032
148	University of Rochester	Rochester	New York	United States	14642
149	Kinston Medical Specialists PA	Kinston	North Carolina	United States	28501
150	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
151	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
152	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
153	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
154	Grant Medical Center	Columbus	Ohio	United States	43215
155	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
156	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
157	Doctors Hospital	Columbus	Ohio	United States	43228
158	Grandview Hospital	Dayton	Ohio	United States	45405
159	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
160	Miami Valley Hospital	Dayton	Ohio	United States	45409
161	Samaritan North Health Center	Dayton	Ohio	United States	45415
162	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45420
163	Grady Memorial Hospital	Delaware	Ohio	United States	43015
164	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
165	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
166	Wayne Hospital	Greenville	Ohio	United States	45331
167	Kettering Medical Center	Kettering	Ohio	United States	45429
168	Fairfield Medical Center	Lancaster	Ohio	United States	43130
169	Saint Rita's Medical Center	Lima	Ohio	United States	45801
170	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
171	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
172	Licking Memorial Hospital	Newark	Ohio	United States	43055
173	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
174	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
175	Upper Valley Medical Center	Troy	Ohio	United States	45373
176	Saint Ann's Hospital	Westerville	Ohio	United States	43081
177	Greene Memorial Hospital	Xenia	Ohio	United States	45385
178	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
179	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
180	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
181	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
182	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
183	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
184	Geisinger Medical Group	State College	Pennsylvania	United States	16801
185	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
186	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
187	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
188	Baylor University Medical Center	Dallas	Texas	United States	75246
189	Audie L Murphy Veterans Affairs Hospital	San Antonio	Texas	United States	78209
190	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas	United States	78229
191	University Hospital	San Antonio	Texas	United States	78229
192	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
193	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
194	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
195	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
196	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
197	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
198	Swedish Medical Center-Edmonds	Edmonds	Washington	United States	98026
199	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
200	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
201	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
202	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
203	Harborview Medical Center	Seattle	Washington	United States	98104
204	Minor and James Medical PLLC	Seattle	Washington	United States	98104
205	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
206	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
207	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
208	University of Washington Medical Center	Seattle	Washington	United States	98195
209	United General Hospital	Sedro-Woolley	Washington	United States	98284
210	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
211	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
212	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
213	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
214	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Przemyslaw Twardowski, Southwest Oncology Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 10, 2016

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01688973
• Other Study ID Numbers: NCI-2012-01641; NCI-2012-01641; S1107; SWOG-S1107; S1107; S1107; U10CA180888; U10CA032102
• First Posted: Sep 20, 2012
• Last Update Posted: Jan 3, 2019
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Arm I (Tivantinib)	Arm II (Tivantinib and Erlotinib Hydrochloride)
Arm/Group Description	Patients receive tivantinib PO BID on days 1-28. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO	Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Period Title: Overall Study
STARTED	27	28
Eligible/Evaluable Patients	25	25
COMPLETED	25	25
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Arm I (Tivantinib)	Arm II (Tivantinib and Erlotinib Hydrochloride)	Total
Arm/Group Description	Patients receive tivantinib PO BID on days 1-28. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO	Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO	Total of all reporting groups
Overall Participants	25	25	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.1	63.6	63.6
Sex: Female, Male (Count of Participants)
Female	6 24%	10 40%	16 32%
Male	19 76%	15 60%	34 68%
Race/Ethnicity, Customized (Count of Participants)
White	19 76%	19 76%	38 76%
Black	6 24%	5 20%	11 22%
Unknown	0 0%	1 4%	1 2%
Histologic Grade (Count of Participants)
Unknown	11 44%	11 44%	22 44%
1	0 0%	0 0%	0 0%
2	3 12%	5 20%	8 16%
3	7 28%	6 24%	13 26%
4	4 16%	3 12%	7 14%
Histologic Subset (Count of Participants)
Pure Papillary	20 80%	23 92%	43 86%
Mixed Histology	5 20%	2 8%	7 14%
Histologic Type (Count of Participants)
Not Assigned	12 48%	14 56%	26 52%
Type I	2 8%	1 4%	3 6%
Type II	11 44%	10 40%	21 42%
Prior Nephrectomy (Count of Participants)
No	4 16%	7 28%	11 22%
Yes	21 84%	18 72%	39 78%
Prior Systemic Therapy (Count of Participants)
None	16 64%	17 68%	33 66%
One	9 36%	8 32%	17 34%
Performance Status (Count of Participants)
0	12 48%	9 36%	21 42%
1	11 44%	13 52%	24 48%
2	2 8%	3 12%	5 10%
3	0 0%	0 0%	0 0%
4	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Response Rate (Confirmed Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors
Description	Best Response is calculated from the sequence of objective statuses. CR: Two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. PR: Two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration, but not qualifying as CR. Stable/no response: At least one objective status of stable/no response documented at least 6 weeks after registration and before progression or symptomatic deterioration, but not qualifying as anything else above. Increasing disease: Objective status of progression within 12 weeks of registration, not qualifying as anything else above. Symptomatic deterioration: Objective status of symptomatic deterioration within 12 weeks of registration, not qualifying as anything else above.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Tivantinib)	Arm II (Tivantinib and Erlotinib Hydrochloride)
Arm/Group Description	Patients receive tivantinib PO BID on days 1-28. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO	Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Measure Participants	25	25
Complete Response	0 0%	0 0%
Partial Response	0 0%	0 0%
Stable/no response	11 44%	13 52%
Increasing disease	14 56%	7 28%
Symptomatic deterioration	0 0%	1 4%
Not Assessable	0 0%	4 16%

2. Secondary Outcome

Title	Frequency and Severity of Toxicities, Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description	This study utilized the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 for toxicity and Serious Adverse Event reporting. Patients were evaluated every two weeks for the first eight weeks and then once every four weeks. If all protocol treatment is delayed more than three weeks, patients were removed from protocol treatment
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All eligible patients who reported adverse events

Arm/Group Title	Arm I (Tivantinib)	Arm II (Tivantinib and Erlotinib Hydrochloride)
Arm/Group Description	Patients receive tivantinib PO BID on days 1-28. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO	Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Measure Participants	25	25
Alanine aminotransferase increased	0 0%	1 4%
Anemia	2 8%	1 4%
Aspartate aminotransferase increased	0 0%	1 4%
Dyspnea	1 4%	1 4%
Erythema multiforme	0 0%	1 4%
Fatigue	0 0%	1 4%
Febrile neutropenia	0 0%	1 4%
Hypertension	1 4%	0 0%
Hypoxia	0 0%	1 4%
Infections and infestations - Other, specify	0 0%	1 4%
Lung infection	0 0%	1 4%
Lymphocyte count decreased	1 4%	0 0%
Myocardial infarction	0 0%	1 4%
Nausea	1 4%	0 0%
Neutrophil count decreased	1 4%	0 0%
Pain in extremity	1 4%	0 0%
Pneumonitis	0 0%	1 4%
Rash acneiform	0 0%	2 8%
Rash maculo-papular	0 0%	1 4%
Stroke	1 4%	0 0%
Weight loss	1 4%	0 0%
White blood cell decreased	1 4%	1 4%

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact.
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Tivantinib)	Arm II (Tivantinib and Erlotinib Hydrochloride)
Arm/Group Description	Patients receive tivantinib PO BID on days 1-28. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO	Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
Measure Participants	25	25
Median (95% Confidence Interval) [months]	2.0	3.9

4. Other Pre-specified Outcome

Title	Number of Participants With c-MET Amplification, Deletion and No Alteration
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Tissue was only obtained from 35 patients. Exome of 16 patients were successfully sequenced using Agilent SureSelect probes. Arms were pooled due to no difference in response rate between the two arms

Arm/Group Title	Pooled Arms
Arm/Group Description	Pooled treatment arms for translational medicine objectives. Arms were pooled due to no difference in response rate between the two arms.
Measure Participants	16
Amplification	6 24%
Deletion	0 0%
No Alteration	10 40%

5. Other Pre-specified Outcome

Title	Number of Participants With EGFR Amplification, Deletion and No Alteration
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Tissue was only obtained from 35 patients. Exome of 16 patients were successfully sequenced using Agilent SureSelect probes.

Arm/Group Title	Pooled Arms
Arm/Group Description	Pooled treatment arms for translational medicine objectives. Arms were pooled due to no difference in response rate between the two arms.
Measure Participants	16
Amplification	3 12%
Deletion	1 4%
No Alteration	12 48%

Adverse Events

Time Frame	Up to 3 years
Adverse Event Reporting Description	This study utilized the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 for toxicity and Serious Adverse Event reporting. Patients were evaluated every two weeks for the first eight weeks and then once every four weeks. If all protocol treatment is delayed more than three weeks, patients were removed from protocol treatment. Adverse events and all-cause mortality is reported for all eligible patients.
Arm/Group Title	Arm I (Tivantinib)		Arm II (Tivantinib and Erlotinib Hydrochloride)
Arm/Group Description	Patients receive tivantinib PO BID on days 1-28. Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO		Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies Tivantinib: Given PO
All Cause Mortality
	Arm I (Tivantinib)		Arm II (Tivantinib and Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/25 (80%)		21/25 (84%)
Serious Adverse Events
	Arm I (Tivantinib)		Arm II (Tivantinib and Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/25 (36%)		16/25 (64%)
Blood and lymphatic system disorders
Anemia	1/25 (4%)		2/25 (8%)
Blood and lymphatic system disorders - Other	0/25 (0%)		1/25 (4%)
Febrile neutropenia	0/25 (0%)		1/25 (4%)
Cardiac disorders
Atrial flutter	0/25 (0%)		1/25 (4%)
Cardiac arrest	1/25 (4%)		0/25 (0%)
Cardiac disorders-Other	0/25 (0%)		1/25 (4%)
Myocardial infarction	0/25 (0%)		1/25 (4%)
Sinus bradycardia	0/25 (0%)		1/25 (4%)
Gastrointestinal disorders
Abdominal distension	0/25 (0%)		1/25 (4%)
Abdominal pain	0/25 (0%)		2/25 (8%)
Constipation	0/25 (0%)		1/25 (4%)
Nausea	0/25 (0%)		1/25 (4%)
Small intestinal obstruction	0/25 (0%)		2/25 (8%)
General disorders
Fatigue	1/25 (4%)		2/25 (8%)
Infections and infestations
Device related infection	0/25 (0%)		1/25 (4%)
Lung infection	0/25 (0%)		1/25 (4%)
Sepsis	0/25 (0%)		1/25 (4%)
Investigations
Alanine aminotransferase increased	0/25 (0%)		2/25 (8%)
Alkaline phosphatase increased	0/25 (0%)		1/25 (4%)
Aspartate aminotransferase increased	0/25 (0%)		1/25 (4%)
Blood bilirubin increased	1/25 (4%)		0/25 (0%)
Platelet count decreased	0/25 (0%)		1/25 (4%)
Weight loss	1/25 (4%)		0/25 (0%)
White blood cell decreased	0/25 (0%)		1/25 (4%)
Metabolism and nutrition disorders
Acidosis	0/25 (0%)		2/25 (8%)
Dehydration	0/25 (0%)		1/25 (4%)
Hyperkalemia	0/25 (0%)		1/25 (4%)
Hypoalbuminemia	0/25 (0%)		1/25 (4%)
Hypokalemia	0/25 (0%)		1/25 (4%)
Hyponatremia	0/25 (0%)		2/25 (8%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/25 (4%)		0/25 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	2/25 (8%)		2/25 (8%)
Nervous system disorders
Dizziness	0/25 (0%)		1/25 (4%)
Intracranial hemorrhage	0/25 (0%)		1/25 (4%)
Stroke	1/25 (4%)		0/25 (0%)
Renal and urinary disorders
Acute kidney injury	0/25 (0%)		1/25 (4%)
Hematuria	1/25 (4%)		1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/25 (16%)		1/25 (4%)
Hypoxia	0/25 (0%)		1/25 (4%)
Pneumonitis	0/25 (0%)		1/25 (4%)
Respiratory failure	0/25 (0%)		2/25 (8%)
Skin and subcutaneous tissue disorders
Rash acneiform	0/25 (0%)		1/25 (4%)
Vascular disorders
Thromboembolic event	1/25 (4%)		1/25 (4%)
Other (Not Including Serious) Adverse Events
	Arm I (Tivantinib)		Arm II (Tivantinib and Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/25 (88%)		23/25 (92%)
Blood and lymphatic system disorders
Anemia	10/25 (40%)		7/25 (28%)
Cardiac disorders
Sinus bradycardia	2/25 (8%)		4/25 (16%)
Gastrointestinal disorders
Abdominal pain	4/25 (16%)		4/25 (16%)
Bloating	3/25 (12%)		0/25 (0%)
Constipation	5/25 (20%)		4/25 (16%)
Diarrhea	4/25 (16%)		9/25 (36%)
Flatulence	1/25 (4%)		3/25 (12%)
Gastroesophageal reflux disease	2/25 (8%)		1/25 (4%)
Gastrointestinal disorders-Other	2/25 (8%)		0/25 (0%)
Mucositis oral	1/25 (4%)		2/25 (8%)
Nausea	11/25 (44%)		14/25 (56%)
Vomiting	3/25 (12%)		6/25 (24%)
General disorders
Chills	2/25 (8%)		0/25 (0%)
Edema limbs	5/25 (20%)		1/25 (4%)
Fatigue	13/25 (52%)		13/25 (52%)
Fever	4/25 (16%)		4/25 (16%)
Flu like symptoms	0/25 (0%)		2/25 (8%)
Localized edema	1/25 (4%)		2/25 (8%)
Non-cardiac chest pain	2/25 (8%)		1/25 (4%)
Pain	4/25 (16%)		2/25 (8%)
Infections and infestations
Upper respiratory infection	2/25 (8%)		1/25 (4%)
Investigations
Alanine aminotransferase increased	2/25 (8%)		5/25 (20%)
Alkaline phosphatase increased	3/25 (12%)		4/25 (16%)
Aspartate aminotransferase increased	3/25 (12%)		5/25 (20%)
Blood bilirubin increased	0/25 (0%)		3/25 (12%)
Creatinine increased	6/25 (24%)		6/25 (24%)
Lymphocyte count decreased	4/25 (16%)		8/25 (32%)
Neutrophil count decreased	2/25 (8%)		0/25 (0%)
Weight gain	3/25 (12%)		2/25 (8%)
Weight loss	2/25 (8%)		5/25 (20%)
White blood cell decreased	3/25 (12%)		2/25 (8%)
Metabolism and nutrition disorders
Anorexia	4/25 (16%)		8/25 (32%)
Hyperglycemia	7/25 (28%)		8/25 (32%)
Hyperkalemia	2/25 (8%)		3/25 (12%)
Hypoalbuminemia	4/25 (16%)		4/25 (16%)
Hypocalcemia	1/25 (4%)		3/25 (12%)
Hypokalemia	2/25 (8%)		2/25 (8%)
Hyponatremia	3/25 (12%)		4/25 (16%)
Musculoskeletal and connective tissue disorders
Back pain	4/25 (16%)		1/25 (4%)
Chest wall pain	2/25 (8%)		0/25 (0%)
Flank pain	2/25 (8%)		0/25 (0%)
Myalgia	2/25 (8%)		0/25 (0%)
Pain in extremity	5/25 (20%)		1/25 (4%)
Nervous system disorders
Dizziness	2/25 (8%)		1/25 (4%)
Dysgeusia	2/25 (8%)		4/25 (16%)
Headache	2/25 (8%)		2/25 (8%)
Peripheral sensory neuropathy	3/25 (12%)		1/25 (4%)
Psychiatric disorders
Anxiety	2/25 (8%)		0/25 (0%)
Depression	2/25 (8%)		1/25 (4%)
Insomnia	3/25 (12%)		0/25 (0%)
Renal and urinary disorders
Hematuria	0/25 (0%)		2/25 (8%)
Proteinuria	0/25 (0%)		2/25 (8%)
Respiratory, thoracic and mediastinal disorders
Cough	5/25 (20%)		5/25 (20%)
Dyspnea	3/25 (12%)		5/25 (20%)
Skin and subcutaneous tissue disorders
Alopecia	5/25 (20%)		2/25 (8%)
Dry skin	1/25 (4%)		3/25 (12%)
Erythema multiforme	0/25 (0%)		2/25 (8%)
Pruritus	0/25 (0%)		2/25 (8%)
Rash acneiform	0/25 (0%)		13/25 (52%)
Rash maculo-papular	3/25 (12%)		3/25 (12%)
Vascular disorders
Hypertension	4/25 (16%)		6/25 (24%)
Hypotension	2/25 (8%)		0/25 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.