Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
NCT-Nummer:
NCT02568267
Studienbeginn:
November 2015
Letztes Update:
22.03.2021
Wirkstoff:
Entrectinib
Indikation (Clinical Trials):
Neoplasms, Carcinoma, Non-Small-Cell Lung, Melanoma, Colorectal Neoplasms, Pancreatic Neoplasms, Sarcoma, Ovarian Neoplasms, Brain Neoplasms, Thyroid Neoplasms, Neuroendocrine Tumors, Cholangiocarcinoma, Salivary Gland Neoplasms, Head and Neck Neoplasms, Lymphoma, Large-Cell, Anaplastic, Thyroid Cancer, Papillary
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 2
Sponsor:
Hoffmann-La Roche
Collaborator:
-
Studienleiter
Study Director
Hoffmann-La Roche
Kontakt
Kontakt:
Phone: 888-662-6728 (U.S. and Canada)
E-Mail: global-roche-genentech-trials@gene.com» Kontaktdaten anzeigen
Studienlocations
(3 von 150)
10117 Berlin
(Berlin)
GermanyZurückgezogen» Google-Maps
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
82131 Gauting
(Bayern)
GermanyZurückgezogen» Google-Maps
37075 Göttingen
(Niedersachsen)
GermanyRekrutierend» Google-Maps
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
50937 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
85338 Goodyear
United StatesZurückgezogen» Google-Maps
85013 Phoenix
United StatesRekrutierend» Google-Maps
85259 Scottsdale
United StatesAktiv, nicht rekrutierend» Google-Maps
91010 Duarte
United StatesRekrutierend» Google-Maps
92037 La Jolla
United StatesAktiv, nicht rekrutierend» Google-Maps
92093 La Jolla
United StatesRekrutierend» Google-Maps
90033 Los Angeles
United StatesRekrutierend» Google-Maps
92868 Orange
United StatesAktiv, nicht rekrutierend» Google-Maps
92108 San Diego
United StatesRekrutierend» Google-Maps
94115 San Francisco
United StatesAktiv, nicht rekrutierend» Google-Maps
90403 Santa Monica
United StatesRekrutierend» Google-Maps
80045 Aurora
United StatesRekrutierend» Google-Maps
06510 New Haven
United StatesAktiv, nicht rekrutierend» Google-Maps
20007 Washington
United StatesAktiv, nicht rekrutierend» Google-Maps
34232 Sarasota
United StatesAktiv, nicht rekrutierend» Google-Maps
33612 Tampa
United StatesRekrutierend» Google-Maps
33331 Weston
United StatesZurückgezogen» Google-Maps
30607 Athens
United StatesAktiv, nicht rekrutierend» Google-Maps
30322 Atlanta
United StatesAktiv, nicht rekrutierend» Google-Maps
30265 Newnan
United StatesAbgeschlossen» Google-Maps
96813 Honolulu
United StatesZurückgezogen» Google-Maps
60611 Chicago
United StatesAktiv, nicht rekrutierend» Google-Maps
60068 Park Ridge
United StatesAbgeschlossen» Google-Maps
60099 Zion
United StatesRekrutierend» Google-Maps
21237 Baltimore
United StatesRekrutierend» Google-Maps
02114 Boston
United StatesRekrutierend» Google-Maps
02215 Boston
United StatesAktiv, nicht rekrutierend» Google-Maps
02215 Boston
United StatesRekrutierend» Google-Maps
48109 Ann Arbor
United StatesAktiv, nicht rekrutierend» Google-Maps
48201 Detroit
United StatesAktiv, nicht rekrutierend» Google-Maps
48202 Detroit
United StatesAktiv, nicht rekrutierend» Google-Maps
55455 Minneapolis
United StatesRekrutierend» Google-Maps
63128 Saint Louis
United StatesAktiv, nicht rekrutierend» Google-Maps
89169 Las Vegas
United StatesRekrutierend» Google-Maps
03756 Lebanon
United StatesZurückgezogen» Google-Maps
11733 East Setauket
United StatesAktiv, nicht rekrutierend» Google-Maps
10065 New York
United StatesRekrutierend» Google-Maps
28204 Charlotte
United StatesRekrutierend» Google-Maps
27710 Durham
United StatesAktiv, nicht rekrutierend» Google-Maps
44195 Cleveland
United StatesZurückgezogen» Google-Maps
43210 Columbus
United StatesRekrutierend» Google-Maps
74133 Tulsa
United StatesAktiv, nicht rekrutierend» Google-Maps
97213 Portland
United StatesZurückgezogen» Google-Maps
97239 Portland
United StatesAktiv, nicht rekrutierend» Google-Maps
19124 Philadelphia
United StatesAbgeschlossen» Google-Maps
75230 Dallas
United StatesRekrutierend» Google-Maps
75390 Dallas
United StatesZurückgezogen» Google-Maps
77030 Houston
United StatesRekrutierend» Google-Maps
76502 Temple
United StatesRekrutierend» Google-Maps
84132 Salt Lake City
United StatesRekrutierend» Google-Maps
22031 Fairfax
United StatesRekrutierend» Google-Maps
23666 Hampton
United StatesRekrutierend» Google-Maps
98195 Seattle
United StatesRekrutierend» Google-Maps
53132 Franklin
United StatesZurückgezogen» Google-Maps
2640 Albury
AustraliaZurückgezogen» Google-Maps
2170 Liverpool
AustraliaRekrutierend» Google-Maps
2305 New Lambton Heights
AustraliaAktiv, nicht rekrutierend» Google-Maps
5042 Bedford Park
AustraliaRekrutierend» Google-Maps
3084 Heidelberg
AustraliaRekrutierend» Google-Maps
2650 Edegem
BelgiumRekrutierend» Google-Maps
100142 Beijing
ChinaNoch nicht rekrutierend» Google-Maps
100730 Beijing
ChinaNoch nicht rekrutierend» Google-Maps
410013 Changsha City
ChinaNoch nicht rekrutierend» Google-Maps
610041 Chengdu
ChinaRekrutierend» Google-Maps
350014 Fuzhou City
ChinaNoch nicht rekrutierend» Google-Maps
510000 Guangzhou
ChinaNoch nicht rekrutierend» Google-Maps
150081 Harbin
ChinaRekrutierend» Google-Maps
200120 Shanghai City
ChinaRekrutierend» Google-Maps
200030 Shanghai
ChinaRekrutierend» Google-Maps
510852 Shenzhen
ChinaNoch nicht rekrutierend» Google-Maps
300060 Tianjin
ChinaNoch nicht rekrutierend» Google-Maps
430023 Wuhan City
ChinaRekrutierend» Google-Maps
310022 Zhejiang
ChinaRekrutierend» Google-Maps
49055 Angers
FranceRekrutierend» Google-Maps
33076 Bordeaux
FranceRekrutierend» Google-Maps
59000 Lille
FranceZurückgezogen» Google-Maps
69373 Lyon
FranceRekrutierend» Google-Maps
13385 Marseille cedex 5
FranceRekrutierend» Google-Maps
13015 Marseille
FranceRekrutierend» Google-Maps
34298 Montpellier cedex 5
FranceRekrutierend» Google-Maps
75908 Paris cedex 15
FranceZurückgezogen» Google-Maps
75231 Paris
FranceRekrutierend» Google-Maps
44805 Saint Herblain
FranceRekrutierend» Google-Maps
31059 Toulouse
FranceRekrutierend» Google-Maps
94805 Villejuif cedex
FranceRekrutierend» Google-Maps
Hong Kong
Hong KongZurückgezogen» Google-Maps
Hong Kong
Hong KongRekrutierend» Google-Maps
Hong Kong
Hong KongRekrutierend» Google-Maps
Kowloon
Hong KongRekrutierend» Google-Maps
123456 Shatin
Hong KongRekrutierend» Google-Maps
80131 Napoli
ItalyRekrutierend» Google-Maps
128 Roma
ItalyRekrutierend» Google-Maps
16132 Genova
ItalyZurückgezogen» Google-Maps
20133 Milano
ItalyRekrutierend» Google-Maps
20162 Milano
ItalyRekrutierend» Google-Maps
10060 Candiolo
ItalyAktiv, nicht rekrutierend» Google-Maps
10043 Orbassano
ItalyZurückgezogen» Google-Maps
10126 Torino
ItalyZurückgezogen» Google-Maps
56126 Pisa
ItalyRekrutierend» Google-Maps
6132 Perugia
ItalyRekrutierend» Google-Maps
35128 Padova
ItalyRekrutierend» Google-Maps
464-8681 Aichi
JapanRekrutierend» Google-Maps
791-0280 Ehime
JapanRekrutierend» Google-Maps
811-1395 Fukuoka
JapanRekrutierend» Google-Maps
673-8558 Hyogo
JapanRekrutierend» Google-Maps
277-8577 Kashiwa-shi
JapanRekrutierend» Google-Maps
981-1293 Miyagi
JapanRekrutierend» Google-Maps
951-8566 Niigata
JapanRekrutierend» Google-Maps
534-0021 Osaka
JapanRekrutierend» Google-Maps
589-8511 Osaka
JapanRekrutierend» Google-Maps
411-8777 Shizuoka
JapanRekrutierend» Google-Maps
28644 Cheongju-si
Korea, Republic ofZurückgezogen» Google-Maps
(0)6351 Seoul
Korea, Republic ofRekrutierend» Google-Maps
03080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
03722 Seoul
Korea, Republic ofRekrutierend» Google-Maps
138-736 Seoul
Korea, Republic ofRekrutierend» Google-Maps
1066 CX Amsterdam
NetherlandsRekrutierend» Google-Maps
2333 ZA Leiden
NetherlandsRekrutierend» Google-Maps
80-214 Gdańsk
PolandRekrutierend» Google-Maps
44-101 Gliwice
PolandRekrutierend» Google-Maps
05-400 Otwock
PolandZurückgezogen» Google-Maps
60-569 Poznań
PolandRekrutierend» Google-Maps
02-781 Warszawa
PolandRekrutierend» Google-Maps
119074 Singapore
SingaporeRekrutierend» Google-Maps
169610 Singapore
SingaporeRekrutierend» Google-Maps
28942 Fuenlabrada
SpainZurückgezogen» Google-Maps
08035 Barcelona
SpainRekrutierend» Google-Maps
28006 Madrid
SpainZurückgezogen» Google-Maps
28034 Madrid
SpainRekrutierend» Google-Maps
28040 Madrid
SpainRekrutierend» Google-Maps
28041 Madrid
SpainRekrutierend» Google-Maps
28046 Madrid
SpainRekrutierend» Google-Maps
28050 Madrid
SpainRekrutierend» Google-Maps
29010 Malaga
SpainRekrutierend» Google-Maps
41013 Sevilla
SpainRekrutierend» Google-Maps
500 Chang Hua
TaiwanZurückgezogen» Google-Maps
407 Taichung
TaiwanZurückgezogen» Google-Maps
70457 Tainan
TaiwanRekrutierend» Google-Maps
11217 Taipei City
TaiwanRekrutierend» Google-Maps
10002 Taipei
TaiwanRekrutierend» Google-Maps
CB2 0QQ Cambridge
United KingdomRekrutierend» Google-Maps
W1G 6AD London
United KingdomRekrutierend» Google-Maps
M2O 4BX Manchester
United KingdomRekrutierend» Google-Maps
Studien-Informationen
Brief Summary:This is an open-label, multicenter, global Phase 2 basket study of entrectinib (RXDX-101) for
the treatment of patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene
fusion. Patients will be assigned to different baskets according to tumor type and gene
fusion.
Ein-/Ausschlusskriterien
Inclusion Criteria:- Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic
solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement
- For patients enrolled via local molecular testing, an archival or fresh tumor tissue
(unless medically contraindicated) is required to be submitted for independent central
molecular testing at Ignyta's CLIA laboratory post-enrollment
- Measurable or evaluable disease
- Patients with CNS involvement, including leptomeningeal carcinomatosis, which is
either asymptomatic or previously-treated and controlled, are allowed
- Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1,
or ALK inhibitors in patients who have tumors that harbor those respective gene
rearrangements)
- Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged
NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are
prohibited.
- At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior
chemotherapy or small molecule targeted therapy
- At least 4 weeks must have elapsed since completion of antibody-directed therapy
- Prior radiotherapy is allowed if more than 14 days have elapsed since the end of
treatment
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and minimum life
expectancy of 4 weeks
- Adequate organ function as defined per protocol
- Ability to swallow entrectinib intact
- Other protocol specified criteria
Exclusion Criteria:
- Current participation in another therapeutic clinical trial
- Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in
patients who have tumors that harbor those respective gene rearrangements
- Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged
NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are
prohibited.
- History of other previous cancer that would interfere with the determination of safety
or efficacy
- Familial or personal history of congenital bone disorders, bone metabolism alterations
or osteopenia
- Incomplete recovery from any surgery
- History of recent (within the past 3 months) symptomatic congestive heart failure or
ejection fraction ≤50% observed during screening for the study
- History of non-pharmacologically induced prolonged QTc interval
- History of additional risk factors for torsades de pointes
- Peripheral neuropathy Grade ≥ 2
- Known active infections
- Active gastrointestinal disease or other malabsorption syndromes
- Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase
inhibitor-induced pneumonitis
- Other protocol specified criteria
Studien-Rationale
Primary outcome:1. Objective Response Rate (Time Frame - Approximately 24 months):
Assessed by blinded independent central review (BICR) using RECIST v1.1
Secondary outcome:
1. Duration of Response (Time Frame - Approximately 24 months):
Assessed by blinded independent central review (BICR) using RECIST v1.1
2. Time to Response (Time Frame - Approximately 24 months):
Assessed by blinded independent central review (BICR) using RECIST v1.1
3. Clinical Benefit Rate (Time Frame - Approximately 24 months):
Assessed by blinded independent central review (BICR) using RECIST v1.1
4. Intracranial Tumor Response (Time Frame - Approximately 24 months):
Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
5. CNS Progression-free Survival (Time Frame - Approximately 24 months):
Assessed by blinded independent central review (BICR) using RANO or RANO-BM, as applicable
6. Progression-free Survival (Time Frame - Approximately 30 months):
Assessed by Kaplan-Meier method
7. Overall Survival (Time Frame - Approximately 36 months):
Assessed by Kaplan-Meier method
8. Population PK (Time Frame - Approximately 24 months):
Assessed by Kaplan-Meier method
9. Adverse Events (Time Frame - Approximately 36 months):
Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE
10. Quality of Life (Time Frame - Approximately 24 months):
Assessed with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the Euro-QoL Group EQ-5D. NSCLC and mCRC patients will complete the lung cancer and colorectal cancer specific modules, QLQ-LC13 and QLQ-CR29, respectively
11. Bone Growth and Bone Mineral Density (Time Frame - Approximately 30 months):
Assessed with DHA scans
12. Bone Biomarkers (Time Frame - Approximately 30 months):
Measured by blood
Studien-Arme
- Experimental: NTRK1/2/3-rearranged NSCLC
Oral entrectinib (RXDX-101) - Experimental: ROS1-rearranged NSCLC
Oral entrectinib (RXDX-101) - Experimental: ALK- or ROS1-rearranged NSCLC
with CNS-only progression previously treated with crizotinib (NOTE: The ALK-rearranged portion of this arm is now closed to enrollment.) Oral entrectinib (RXDX-101) - Experimental: NTRK/1/2/3-rearranged mCRC
Oral entrectinib (RXDX-101) - Experimental: ROS1-rearranged mCRC
Oral entrectinib (RXDX-101) - Experimental: ALK-rearranged mCRC
Oral entrectinib (RXDX-101) - Experimental: NTRK1/2/3-rearranged other solid tumor
Oral entrectinib (RXDX-101) - Experimental: ROS1-rearranged other solid tumor
Oral entrectinib (RXDX-101) - Experimental: ALK-rearranged other solid tumor
Oral entrectinib (RXDX-101)
Geprüfte Regime
- Entrectinib (RXDX-101):
TrkA/B/C, ROS1, and ALK inhibitor
Quelle: ClinicalTrials.gov