Clinical Trials List
Protocol NumberRXDX-101-02
NCT Number(ClinicalTrials.gov Identfier)NCT02568267
2017-03-14 - 2025-05-13
Phase II
Recruiting3
Terminated2
ICD-9199.0
Disseminated malignant neoplasm
An Open-Label, Multicenter, Global Phase 2 Basket Study of for the Treatment of Patients with Locally Advanced or Metastatic Solid Tumors that Entrectinib Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
F. Hoffmann-La Roche Ltd
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 張毓帆 無
- 趙恒勝 無
- Ming-Huang Chen 無
- Yi-Ping Hung 無
- Hsu-ching Huang 無
- Chueh-Chuan Yen 無
- Chi-Lu Chiang 無
- 郭懿萱 無
- 蔡俊明 無
- Chao-Hua Chiu 無
- Chia-I Shen 無
- Yi-Jen Chen 無
- 蕭慈慧 無
The Actual Total Number of Participants Enrolled
10 Recruiting
Audit
CRO
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Sin-Syue Li 無
- Chia-Jui Yen 無
- Shang-Yin Wu 無
- Wei-Pang Chung 無
- Yu-Min Yeh 無
- Wen-Pin Su 無
- Wu-Chou Su 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Chong-Jen Yu 無
- 許嘉林 無
- Kun-Huei Yeh 無
- CHAO-CHI HO CHAO-CHI HO 無
- 徐偉勛 無
- James Chih-Hsin Yang 無
- Jih-Hsiang Lee 無
- Wei-Wu Chen 無
- 廖唯昱 無
- JIN-YUAN SHIH 無
- 陳國興 無
- 廖斌志 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Locally Advanced or Metastatic Solid Tumors that Entrectinib Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements
Objectives
Primary Objective
To determine the objective response rate (ORR) of entrectinib, as assessed by BICR,
in each patient population basket of solid tumors that harbor an NTRK1/2/3, ROS1, or
ALK gene rearrangement.
Secondary Objectives
To determine the duration of response (DOR), time to response (TTR), and clinical
benefit rate (CBR) of entrectinib, as assessed by BICR, in each patient population
basket of solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene rearrangement
To determine the intracranial tumor response of entrectinib and CNS progression-free
survival (CNS-PFS) in patients presenting with measurable brain metastases at
baseline, as assessed by BICR using RANO-BM
To estimate the progression-free survival (PFS) and overall survival (OS) of patients
with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene rearrangement
treated with entrectinib
To evaluate the safety and tolerability of entrectinib when administered at the RP2D
in patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene
rearrangement
To assess the population pharmacokinetics (PK) of entrectinib and to explore
correlations between PK, response, and/or safety findings in patients with
NTRK1/2/3, ROS1, or ALK gene rearrangements
To evaluate the effect of entrectinib on ventricular repolarization
To assess treatment-related symptoms and general health status using validated
instruments of patient reported outcomes
Test Drug
Entrectinib
Active Ingredient
Entrectinib
Dosage Form
capsule
Dosage
200mg
Endpoints
Primary Endpoint:
Objective Response Rate (ORR), defined as the proportion of
patients with complete response (CR) or partial response (PR); a
confirmed response is a response that persists on repeat-imaging
(≥ 4 weeks after initial documentation of response)
Secondary Endpoints:
Duration of Response (DOR), defined from the first date of
objective response (either CR or PR) to first documentation of
radiographic disease progression
Time to Response (TTR), defined as the time from the first dose
of entrectinib to the first documentation of objective response
(either CR or PR)
Clinical Benefit Rate (CBR), defined as the proportion of patients
with CR, PR, or stable disease (SD) at 6 months after the first
dose of entrectinib
Intracranial tumor response in patients with measurable brain
metastases, as determined by BICR using RANO-BM
CNS Progression-Free Survival (CNS-PFS) in patients with
measurable brain metastases, defined as the time from the first
dose of entrectinib to first documentation of radiographic CNS
progression (as determined by BICR using RANO-BM) or death
due to any cause, whichever occurs first
Progression-Free Survival (PFS), defined as the time from the
first dose of entrectinib to first documentation of radiographic
disease progression or death due to any cause, whichever occurs
first
Overall Survival (OS), defined as the time from the first dose of
entrectinib to the date of death due to any cause
Type, incidence, severity, timing, seriousness, and relatedness of
adverse events and laboratory abnormalities
Population PK
Ventricular repolarization
Quality-of-life and health status
Exploratory Endpoints
Analysis of potential differences in clinicopathologic
presentation and response to entrectinib among the various tumor
types harboring NTRK1/2/3, ROS1, or ALK gene rearrangements
Analysis of potential differences in clinicopathologic
presentation and response to entrectinib among the various fusion
partner variants of NTRK1/2/3, ROS1, or ALK gene
rearrangements
Potential mechanisms of resistance to entrectinib
Objective Response Rate (ORR), defined as the proportion of
patients with complete response (CR) or partial response (PR); a
confirmed response is a response that persists on repeat-imaging
(≥ 4 weeks after initial documentation of response)
Secondary Endpoints:
Duration of Response (DOR), defined from the first date of
objective response (either CR or PR) to first documentation of
radiographic disease progression
Time to Response (TTR), defined as the time from the first dose
of entrectinib to the first documentation of objective response
(either CR or PR)
Clinical Benefit Rate (CBR), defined as the proportion of patients
with CR, PR, or stable disease (SD) at 6 months after the first
dose of entrectinib
Intracranial tumor response in patients with measurable brain
metastases, as determined by BICR using RANO-BM
CNS Progression-Free Survival (CNS-PFS) in patients with
measurable brain metastases, defined as the time from the first
dose of entrectinib to first documentation of radiographic CNS
progression (as determined by BICR using RANO-BM) or death
due to any cause, whichever occurs first
Progression-Free Survival (PFS), defined as the time from the
first dose of entrectinib to first documentation of radiographic
disease progression or death due to any cause, whichever occurs
first
Overall Survival (OS), defined as the time from the first dose of
entrectinib to the date of death due to any cause
Type, incidence, severity, timing, seriousness, and relatedness of
adverse events and laboratory abnormalities
Population PK
Ventricular repolarization
Quality-of-life and health status
Exploratory Endpoints
Analysis of potential differences in clinicopathologic
presentation and response to entrectinib among the various tumor
types harboring NTRK1/2/3, ROS1, or ALK gene rearrangements
Analysis of potential differences in clinicopathologic
presentation and response to entrectinib among the various fusion
partner variants of NTRK1/2/3, ROS1, or ALK gene
rearrangements
Potential mechanisms of resistance to entrectinib
Inclution Criteria
Inclusion Criteria
1. Histologically- or cytologically-confirmed diagnosis of locally
advanced or metastatic solid tumor that harbors an NTRK1/2/3,
ROS1, or ALK gene rearrangement as determined by any nucleic
acid-based diagnostic testing method (e.g., NGS, Sanger, RTPCR, NanoString, EdgeSeq; FISH is not an acceptable method)
performed at a local CLIA-certified or equivalently-accredited
diagnostic laboratory.
Note: Patients diagnosed with anaplastic large cell lymphoma
(ALCL) harboring a gene rearrangement of interest may be
eligible provided they meet all other inclusion/exclusion criteria
2. 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
3. Measurable disease as assessed locally using RECIST v1.1.
Note: Patients with non-measurable disease (evaluable disease
only) will be eligible for enrollment in the non-measurable
disease basket and will mainly contribute to assessment of safety,
PK, and other secondary endpoints.
4. Patients with CNS involvement, including leptomeningeal
carcinomatosis, which is either asymptomatic or previouslytreated and controlled, are allowed. The use of seizure
prophylaxis is allowed as long as patients are taking
non-enzyme-inducing anti-epileptic drugs (non-EIAEDs). If
patients were previously on EIAEDs and these have been
discontinued, they must have been discontinued for at least 2
weeks prior to the start of entrectinib treatment. If patients
require an anti-epileptic medication, a CYP3A4 non-EIAED can
be used such as levetiracetam, valproic acid, gabapentin,
topiramate, or lacosamide. Moderate inducers of CYP450, such
as dexamethasone or other glucocorticoids, may be used at the
discretion of the Investigator. Patients requiring steroids must be
at stable or decreasing doses for at least 2 weeks prior to the start
of entrectinib treatment.
5. 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 in ALK- or
ROS1-rearranged NSCLC patients presenting with CNS-only
progression.
6. At least 2 weeks or 5 half-lives, whichever is shorter, must have
elapsed after prior chemotherapy or small molecule targeted
therapy, respectively, at the time of the start of entrectinib
treatment.
7. At least 4 weeks must have elapsed since completion of
antibody-directed therapy at the time of the start of entrectinib
treatment.
8. Prior radiotherapy is allowed if more than 14 days have elapsed
since the end of treatment. Patients who received brain
irradiation must have completed whole brain radiotherapy at least
14 days prior and/or stereotactic radiosurgery at least 7 days prior
to the start of entrectinib treatment.
9. Age ≥ 18 years.
10. Eastern Cooperative Oncology Group (ECOG) performance
status ≤ 2.
11. Adequate organ function as defined by the following criteria:
Serum aspartate transaminase (AST; serum glutamic
oxaloacetic transaminase (SGOT)) and serum alanine
transaminase (ALT; serum glutamic pyruvic transaminase
(SGPT)) ≤ 3.0 × upper limit of normal (ULN); ≤ 5.0 × ULN if
liver metastases are present
Total serum bilirubin ≤ 2.0 × ULN; patients with a known
history of Gilbert’s syndrome and/or isolated elevations of
indirect bilirubin are eligible
Serum creatinine within normal limits or creatinine clearance
≥ 30 mL/min
12. Females of childbearing potential must have a negative serum
pregnancy test during Screening and must not be breastfeeding or
intending to become pregnant during the study.
13. Ability to swallow entrectinib intact without chewing, crushing,
or opening the capsules.
14. Willingness to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
15. Signed and dated informed consent document indicating that the
patient (or legally acceptable representative) has been informed
of all pertinent aspects of the trial prior to the start of entrectinib
treatment.
1. Histologically- or cytologically-confirmed diagnosis of locally
advanced or metastatic solid tumor that harbors an NTRK1/2/3,
ROS1, or ALK gene rearrangement as determined by any nucleic
acid-based diagnostic testing method (e.g., NGS, Sanger, RTPCR, NanoString, EdgeSeq; FISH is not an acceptable method)
performed at a local CLIA-certified or equivalently-accredited
diagnostic laboratory.
Note: Patients diagnosed with anaplastic large cell lymphoma
(ALCL) harboring a gene rearrangement of interest may be
eligible provided they meet all other inclusion/exclusion criteria
2. 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
3. Measurable disease as assessed locally using RECIST v1.1.
Note: Patients with non-measurable disease (evaluable disease
only) will be eligible for enrollment in the non-measurable
disease basket and will mainly contribute to assessment of safety,
PK, and other secondary endpoints.
4. Patients with CNS involvement, including leptomeningeal
carcinomatosis, which is either asymptomatic or previouslytreated and controlled, are allowed. The use of seizure
prophylaxis is allowed as long as patients are taking
non-enzyme-inducing anti-epileptic drugs (non-EIAEDs). If
patients were previously on EIAEDs and these have been
discontinued, they must have been discontinued for at least 2
weeks prior to the start of entrectinib treatment. If patients
require an anti-epileptic medication, a CYP3A4 non-EIAED can
be used such as levetiracetam, valproic acid, gabapentin,
topiramate, or lacosamide. Moderate inducers of CYP450, such
as dexamethasone or other glucocorticoids, may be used at the
discretion of the Investigator. Patients requiring steroids must be
at stable or decreasing doses for at least 2 weeks prior to the start
of entrectinib treatment.
5. 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 in ALK- or
ROS1-rearranged NSCLC patients presenting with CNS-only
progression.
6. At least 2 weeks or 5 half-lives, whichever is shorter, must have
elapsed after prior chemotherapy or small molecule targeted
therapy, respectively, at the time of the start of entrectinib
treatment.
7. At least 4 weeks must have elapsed since completion of
antibody-directed therapy at the time of the start of entrectinib
treatment.
8. Prior radiotherapy is allowed if more than 14 days have elapsed
since the end of treatment. Patients who received brain
irradiation must have completed whole brain radiotherapy at least
14 days prior and/or stereotactic radiosurgery at least 7 days prior
to the start of entrectinib treatment.
9. Age ≥ 18 years.
10. Eastern Cooperative Oncology Group (ECOG) performance
status ≤ 2.
11. Adequate organ function as defined by the following criteria:
Serum aspartate transaminase (AST; serum glutamic
oxaloacetic transaminase (SGOT)) and serum alanine
transaminase (ALT; serum glutamic pyruvic transaminase
(SGPT)) ≤ 3.0 × upper limit of normal (ULN); ≤ 5.0 × ULN if
liver metastases are present
Total serum bilirubin ≤ 2.0 × ULN; patients with a known
history of Gilbert’s syndrome and/or isolated elevations of
indirect bilirubin are eligible
Serum creatinine within normal limits or creatinine clearance
≥ 30 mL/min
12. Females of childbearing potential must have a negative serum
pregnancy test during Screening and must not be breastfeeding or
intending to become pregnant during the study.
13. Ability to swallow entrectinib intact without chewing, crushing,
or opening the capsules.
14. Willingness to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
15. Signed and dated informed consent document indicating that the
patient (or legally acceptable representative) has been informed
of all pertinent aspects of the trial prior to the start of entrectinib
treatment.
Exclusion Criteria
Exclusion Criteria
1. Current participation in another therapeutic clinical trial.
2. 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 in ALK- or
ROS1-rearranged NSCLC patients presenting with CNS-only
progression.
3. History of other previous cancer that would interfere with the
determination of safety or efficacy of entrectinib with respect to
the qualifying solid tumor malignancy.
4. Incomplete recovery from any surgery prior to the start of
entrectinib treatment that would interfere with the determination
of safety or efficacy of entrectinib.
5. Any condition (in the past 3 months) that would interfere with
the determination of safety or efficacy of entrectinib: myocardial
infarction, unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular
accident or transient ischemic attack, stroke, symptomatic
bradycardia, or uncontrolled arrhythmias requiring medication.
6. History of non-pharmacologically induced prolonged QTc
interval (e.g., repeated demonstration of a QTc interval
> 500 milliseconds from ECGs performed at least 24 hours
apart).
7. History of additional risk factors for torsade de pointes (e.g.,
family history of long QT syndrome).
8. Peripheral neuropathy Grade ≥ 2.
9. Known active infections that would interfere with the assessment
of safety or efficacy of entrectinib (bacterial, fungal, or viral,
including human immunodeficiency virus positive).
10. Active gastrointestinal disease (e.g., Crohn’s disease, ulcerative
colitis, or short gut syndrome) or other malabsorption syndromes
that would reasonably impact drug absorption.
11. Known interstitial lung disease, interstitial fibrosis, or history of
tyrosine kinase inhibitor-induced pneumonitis.
12. Other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with
study participation or study drug administration or may interfere
with the interpretation of study results and, in the judgment of the
Investigator, would make the patient inappropriate for entry into
this study or could compromise protocol objectives in the opinion
of the Investigator and/or the Sponsor.
1. Current participation in another therapeutic clinical trial.
2. 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 in ALK- or
ROS1-rearranged NSCLC patients presenting with CNS-only
progression.
3. History of other previous cancer that would interfere with the
determination of safety or efficacy of entrectinib with respect to
the qualifying solid tumor malignancy.
4. Incomplete recovery from any surgery prior to the start of
entrectinib treatment that would interfere with the determination
of safety or efficacy of entrectinib.
5. Any condition (in the past 3 months) that would interfere with
the determination of safety or efficacy of entrectinib: myocardial
infarction, unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular
accident or transient ischemic attack, stroke, symptomatic
bradycardia, or uncontrolled arrhythmias requiring medication.
6. History of non-pharmacologically induced prolonged QTc
interval (e.g., repeated demonstration of a QTc interval
> 500 milliseconds from ECGs performed at least 24 hours
apart).
7. History of additional risk factors for torsade de pointes (e.g.,
family history of long QT syndrome).
8. Peripheral neuropathy Grade ≥ 2.
9. Known active infections that would interfere with the assessment
of safety or efficacy of entrectinib (bacterial, fungal, or viral,
including human immunodeficiency virus positive).
10. Active gastrointestinal disease (e.g., Crohn’s disease, ulcerative
colitis, or short gut syndrome) or other malabsorption syndromes
that would reasonably impact drug absorption.
11. Known interstitial lung disease, interstitial fibrosis, or history of
tyrosine kinase inhibitor-induced pneumonitis.
12. Other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with
study participation or study drug administration or may interfere
with the interpretation of study results and, in the judgment of the
Investigator, would make the patient inappropriate for entry into
this study or could compromise protocol objectives in the opinion
of the Investigator and/or the Sponsor.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
600 participants
