AIM-HN/SEQ-HN: Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy

Sponsor

Kura Oncology, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03719690

Collaborator

(none)

284

Enrollment

132

Locations

Arms

41.8

Anticipated Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN). The first cohort will assess the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations. The second study cohort, SEQ-HN, is an observational sub-study and includes 2 types of patients: (1) the historical record of first line therapy in subjects with HRAS mutant HNSCC participating in Cohort 1 in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

Condition or Disease	Intervention/Treatment	Phase
HRAS Gene Mutation HNSCC	Drug: Tipifarnib Device: HRAS Detection Assay	Phase 2

Detailed Description

KO-TIP-007 is an international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on response to first line systemic therapies for HNSCC (SEQ-HN). KO-TIP-007 has 2 study cohorts. The first study cohort, named AIM-HN, includes HNSCC subjects with HRAS mutations. AIM-HN subjects will receive treatment with tipifarnib and the outcome of this cohort will be evaluated for ORR by an independent review facility.

The second study cohort, SEQ-HN, is an observational sub-study and includes 2 types of patients: (1) the historical record of first line therapy in AIM-HN (HRAS mutant HNSCC) subjects in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

HNSCC patients in whom HRAS mutations are identified and who meet eligibility criteria will be offered participation in AIM-HN. HNSCC patients in whom HRAS mutations are not identified may participate in SEQ-HN only. These patients will be followed and the comparison of outcomes of HRAS mutant and HRAS wild type HNSCC will address the exploratory objective to determine the effect of HRAS mutation on the ORR of first line systemic therapy in patients with recurrent/metastatic HNSCC. Outcome data from subsequent lines of therapy will be collected.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

284 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) With HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)

Actual Study Start Date :

Nov 5, 2018

Anticipated Primary Completion Date :

May 1, 2021

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AIM-HN Tipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles	Drug: Tipifarnib Tablet for oral administration Device: HRAS Detection Assay In Vitro Assay to detect HRAS mutations
No Intervention: SEQ-HN To obtain historical information of first line therapy in subjects enrolled in AIM-HN, in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

Arm

Intervention/Treatment

Experimental: AIM-HN

Tipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles

Drug: Tipifarnib

Tablet for oral administration

Device: HRAS Detection Assay

In Vitro Assay to detect HRAS mutations

No Intervention: SEQ-HN

To obtain historical information of first line therapy in subjects enrolled in AIM-HN, in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

Outcome Measures

Primary Outcome Measures

Objective Response Rate in High Variable Allele Frequency (VAF) population [2 years]
complete response and partial response

Secondary Outcome Measures

Objective Response Rate in any VAF population [2 years]
Determine anti-tumor activity of tipifarnib
Duration of Response in High VAF population [2 years]
Determine anti-tumor activity of tipifarnib
Duration of Response in any VAF population [2 years]
Determine anti-tumor activity of tipifarnib
Progression Free Survival in both high VAF and all VAF populations [6 and 9 months]
Determine anti-tumor activity of tipifarnib
Overall survival in both high VAF and all VAF populations [1 year]
Determine anti-tumor activity of tipifarnib
Overall survival in both high VAF and all VAF populations [2 years]
Determine anti-tumor activity of tipifarnib
Investigate safety and tolerability of tipifarnib according to NCI CTCAE v5.0 [30 days after treatment discontinuation]
Incidence of adverse events, incidence of abnormal laboratory test results, abnormal vital signs, and abnormal ECG results
Time to Response in both high VAF and all VAF populations [2 years]
Determine anti-tumor activity of tipifarnib
Time to Progression in both high VAF and all VAF populations [2 years]
Determine anti-tumor activity of tipifarnib
Investigate effects of tipifarnib treatment on quality of life using EORTC QLQ-H&N35 [2 years]
Measured by changes of quality of life using the EORTC QLQ-H&N35
Evaluate the concentration of tipifarnib [pharmacokinetics (PK)] in blood samples over time [6 months]
Measured by blood samples collected during the first 6 cycles of treatment
Investigate effects of tipifarnib treatment on quality of life using EQ-5D-5L [2 years]
Measured by changes of quality of life using the EQ-5D-5L.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

AIM-HN

At least 18 years of age.
Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
Documented treatment failure from most recent prior therapy (e.g. tumor progression, clinical deterioration, or recurrence), and from at least one prior platinum-containing regimen, in any treatment setting.
Known tumor missense HRAS mutation.
Measurable disease by RECIST v1.1.
ECOG performance status of 0-1.
Acceptable liver, renal and hematological function
Other protocol defined inclusion criteria may apply.

Exclusion Criteria:

Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
Received treatment for unstable angina within prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy. Known history of infection with human immunodeficiency virus or an active infection with hepatitis B or hepatitis C.
Received treatment for non-cancer related liver disease within prior year.
Other protocol defined exclusion criteria may apply

Inclusion Criteria: SEQ-HN

At least 18 years of age.
Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.
Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC.
HRAS wildtype (i.e., have no identified tumor missense HRAS mutation).
Other protocol defined inclusion criteria may apply

Exclusion Criteria: SEQ-HN

Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
Other protocol defined exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	UCLA - Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
3	UCSF - Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94158
4	The Oncology Institute of Hope and Innovation - Anaheim	Whittier	California	United States	90603
5	Miami Cancer Institute	Miami	Florida	United States	33176
6	University of South Florida H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
7	Winship Cancer Institute	Atlanta	Georgia	United States	30322
8	University of Chicago	Chicago	Illinois	United States	60637
9	University Of Kansas Medical Center	Westwood	Kansas	United States	66205
10	University of Kentucky Markey Cancer Center	Lexington	Kentucky	United States	40536
11	Norton Cancer Institute	Louisville	Kentucky	United States	40202
12	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
13	Marlene and Stewart Greenebaum Cancer Center	Baltimore	Maryland	United States	21287
14	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
15	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
16	Mayo Clinic	Rochester	Minnesota	United States	55905
17	Siteman Cancer Center - Washington University Medical Campus	Saint Louis	Missouri	United States	63129
18	New York University Langone Medical Center	New York	New York	United States	10016
19	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
20	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
21	The Ohio State University	Columbus	Ohio	United States	43210
22	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
23	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
24	Vanderbilt University Medical Center-Vanderbilt Ingram Cancer Center	Nashville	Tennessee	United States	37232
25	San Antonio Military Medical Center	Fort Sam Houston	Texas	United States	78234
26	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
27	University of Texas Health San Antonio - Mays Cancer Center	San Antonio	Texas	United States	78229
28	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
29	University of Wisconsin	Madison	Wisconsin	United States	53705
30	Peter MacCallum Cancer Centre	Melbourne		Australia	3000
31	Royal North Shore Hospital	Saint Leonards		Australia	2065
32	Allgemeines Krankenhaus der Stadt Wien	Wien		Austria	1090
33	Hanusch Krankenhaus Wiener Gebietskrankenkasse	Wien		Austria	1140
34	Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne	Yvoir	Namur	Belgium	5530
35	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerpen		Belgium	2020
36	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
37	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
38	Universitair Ziekenhuis Leuven	Leuven		Belgium	3000
39	Rigshospitalet	Copenhagen		Denmark	2100
40	Herlev Hospital	Herlev		Denmark	2730
41	Charité Universitätsmedizin Berlin	Berlin		Germany	12203
42	Universitätsklinikum Leipzig	Leipzig		Germany	04103
43	Universitätsmedizin Mannheim	Mannheim		Germany	68167
44	Universitätsklinikum Würzburg	Würzburg		Germany	97080
45	University General Hospital of Athens Attikon	Chaidari		Greece	12462
46	University General Hospital of Larissa	Larissa		Greece	41110
47	Bioclinic - Thessaloniki	Thessaloniki		Greece	54622
48	Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi	Bologna		Italy	40138
49	Azienda Ospedaliera S. Croce e Carle Cuneo	Cuneo		Italy	12100
50	Ospedale Mater Salutis di Legnago	Legnago		Italy	37045
51	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola		Italy	47014
52	Fondazione IRCCS - Istituto Nazionale dei Tumori - Milano	Milano		Italy	20133
53	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli		Italy	80131
54	Azienda Ospedaliera Universitaria Senese-L'ospedale Santa Maria alle Scotte	Siena		Italy	53100
55	National Cancer Center	Goyang-si		Korea, Republic of	10408
56	Chonbuk National University Hospital	Jeonju		Korea, Republic of	54907
57	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
58	Yonsei University Health System Severance Hospital	Seoul		Korea, Republic of	03722
59	Asan Medical Center	Seoul		Korea, Republic of	05505
60	Samsung Medical Center	Seoul		Korea, Republic of	06351
61	The Catholic University of Korea - Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
62	The Catholic University of Korea St. Vincent's Hospital	Suwon		Korea, Republic of	16247
63	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
64	Institut Kanser Negara	Putrajaya		Malaysia	62250
65	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 GZ
66	Maastricht University Medical Centre	Maastricht		Netherlands	6229 HX
67	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3584 CX
68	Haukeland Universitetssjukehus	Bergen		Norway	1521
69	Radiumhospitalet	Oslo		Norway	0379
70	Oncology Center #2	Sochi	Krasnodar Region	Russian Federation
71	Clinical Hospital #1, Department of Maxillofacial Surgery	Sterlitamak	Republic Of Bashkortostan	Russian Federation	453120
72	Republican Clinical Oncology Center, Chemotherapy Department #3	Kazan	Republic Of Tatarstan	Russian Federation	420029
73	Arkhangelsk Clinical Oncology Center, Department of Chemotherapy	Arkhangelsk		Russian Federation	163045
74	Chelyabinsk Regional Clinical Oncology and Nuclear Medicine Center	Chelyabinsk		Russian Federation	454087
75	Ivanovo Regional Oncology Center	Ivanovo		Russian Federation	153040
76	Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center, Chemotherapy Department	Krasnoyarsk		Russian Federation	660133
77	National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Department of Chemotherapy	Moscow		Russian Federation	125284
78	Hadassah Medical LTD	Moscow		Russian Federation
79	Clinical Oncology Center, Chemotherapy Department for Children and Adults	Omsk		Russian Federation	644046
80	Pyatigorsk Interdistrict Oncology Center	Pyatigorsk		Russian Federation	357502
81	National Medical Research Center for Oncology, Department of General Oncology and Chemotherapy	Rostov-on-Don		Russian Federation	344037
82	Railway Clinical Hospital under OAO Russian Railways	St. Petersburg		Russian Federation	195271
83	Oncology Center of Moskovskiy District, Oncology Department	St. Petersburg		Russian Federation	196247
84	Private Medical Institution "EVROMEDSERVIS"	St. Petersburg		Russian Federation	196603
85	N.N. Petrov National Medical Research Center of Oncology, Head and Neck Surgery Department	St. Petersburg		Russian Federation	197758
86	Republican Clinical Oncology Center, Chemotherapy Department, Head and Neck Oncosurgery Department	Ufa		Russian Federation	450054
87	Regional Clinical Oncology Hospital, Department of Chemotherapy	Yaroslavl		Russian Federation	150040
88	Hospital del Mar - Parc de Salut Mar	Barcelona		Spain	08003
89	Hospital de la Santa Creu i de Sant Pau	Barcelona		Spain	08025
90	Hospital Universitari Vall d'Hebrón	Barcelona		Spain	08035
91	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
92	Hospital Duran i Reynals	Barcelona		Spain	08908
93	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
94	Hospital Universitario La Paz	Madrid		Spain	28046
95	HM Centro Integral Oncológico Clara Campal	Madrid		Spain	28050
96	Hospital Costa Del Sol	Marbella		Spain	29603
97	Hospital Universitario Virgen de la Victoria	Málaga		Spain	29010
98	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
99	Hospital Clínico Universitario de Santiago de Compostela	Santiago De Compostela		Spain	15707
100	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
101	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
102	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
103	Changhua Christian Hospital	Changhua		Taiwan	500
104	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	83301
105	Chang Gung Medical Foundation Keelung Chang Gung Memorial Hospital	Keelung		Taiwan	20442
106	China Medical University Hospital	Taichung		Taiwan	40447
107	Taichung Veterans General Hospital	Taichung		Taiwan	407
108	National Cheng Kung University Hospital	Tainan		Taiwan	70403
109	Mackay Memorial Hospital	Taipei		Taiwan	10099
110	National Taiwan University Hospital	Taipei		Taiwan	100
111	Chang Gung Memorial Hospital	Taoyuan		Taiwan	33305
112	King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
113	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai		Thailand	50200
114	Songklanagarind Hospital	Hat Yai		Thailand	90110
115	Chernihiv Medical Center of Modern Oncology, Department of Head and Neck Tumors and Reconstructive Surgery	Chernihiv		Ukraine	14029
116	Regional Public Non-Profit Enterprise "Bukovyna Clinical Oncology Center", Day Care Unit	Chernivtsi		Ukraine	58013
117	Medical Center "MEDICAL PLAZA" of "ECODNIPRO" LLC	Dnipro		Ukraine	49000
118	Public Enterprise "Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital" under Dnipropetrovsk Regional Council, Department of Otolaryngology #2 (oncologic)	Dnipro		Ukraine	49005
119	Prykarpattia Clinical Oncology Center under Ivano-Frankivsk Regional Council, Surgery Department #2	Ivano-Frankivsk		Ukraine	76018
120	State Organization "Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine", Department of Clinical Oncology and Hematology	Kharkiv		Ukraine	61024
121	Communal Non-Profit Enterprise "Regional Center of Oncology", Head and Neck Oncosurgery Department	Kharkiv		Ukraine	61070
122	Medical Center VERUM, LLC	Kyiv		Ukraine	03039
123	Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital", Surgery Department #1	Lviv		Ukraine	79010
124	Sumy Regional Clinical Oncology Center, Oncothoracic Department	Sumy		Ukraine	40022
125	Public Non-Profit Enterprise Ternopil Regional Clinical Oncology Center, Department of Chemotherapy	Ternopil		Ukraine	46023
126	Medical Center ONCOLIFE, LLC	Zaporizhzhia		Ukraine	69059
127	Guy's and Saint Thomas' NHS Foundation Trust	London	England	United Kingdom	SE1 9RT
128	NHS Greater Glasgow and Clyde	Glasgow		United Kingdom	G12 0XH
129	University College London Hospitals NHS Foundation Trust	London		United Kingdom	NW1 2BU
130	The Royal Marsden NHS Foundation Trust	London		United Kingdom	SW3 6JJ
131	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
132	The Royal Marsden NHS Foundation Trust	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

Kura Oncology, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Kura Oncology, Inc.

ClinicalTrials.gov Identifier:

NCT03719690

Other Study ID Numbers:

KO-TIP-007

First Posted:

Oct 25, 2018

Last Update Posted:

Feb 25, 2021

Last Verified:

Feb 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Kura Oncology, Inc.

TIPIFARNIB

HEAD AND NECK CANCER

Additional relevant MeSH terms:

Squamous Cell Carcinoma of Head and Neck

Tipifarnib

Study Results

No Results Posted as of Feb 25, 2021