Clinical Trials List
Protocol NumberCO-1686-020
NCT Number(ClinicalTrials.gov Identfier)NCT02322281
2015-09-09 - 2017-11-30
Phase III
Terminated5
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
TIGER-3: A Phase 3, Open-label, Multicenter, Randomized Study of Oral Rociletinib (CO-1686) Monotherapy Versus Single-agent Cytotoxic Chemotherapy in Patients with Mutant EGFR Non-small Cell Lung Cancer (NSCLC) after Failure of at Least 1 Previous EGFR-directed Tyrosine Kinase Inhibitor (TKI) and Platinumdoublet Chemotherapy
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Clovis Oncology, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- TSUNG -YING YANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chao-Hua Chiu Division of Thoracic Medicine
- Jen-Fu Shih Division of Thoracic Medicine
- 吳杰鴻 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
3 Stop recruiting
Audit
None
Co-Principal Investigator
- 廖偉志 Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- Chia-Hsiang Li Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Chong-Jen Yu Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- 許嘉林 Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- 廖唯昱 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Non-Small Cell Lung Cancer (NSCLC)
Objectives
To compare the anti-tumor efficacy of oral single-agent rociletinib, as measured
by investigator assessment of the progression-free survival (PFS), with that of
single-agent cytotoxic chemotherapy in patients with EGFR-mutated,
advanced/metastatic NSCLC after failure of at least 1 previous EGFR-directed
TKI and at least 1 line of platinum-containing doublet chemotherapy
Test Drug
CO-1686 Hydrobromide Film-Coated Tablet
Active Ingredient
Hydrobromide
Dosage Form
Tablet
Dosage
125 and 250
Endpoints
Primary Endpoint:
• PFS according to RECIST Version 1.111 as determined by investigator
assessment (invPFS)
Secondary Endpoints:
• ORR, DR, and DCR according to RECIST Version 1.1 as determined by
investigator assessment
• OS
• Treatment-emergent adverse events (AEs), laboratory abnormalities, and
electrocardiogram (ECG) abnormalities
• Plasma PK parameters for rociletinib based on sparse sampling
• PFS according to RECIST Version 1.111 as determined by investigator
assessment (invPFS)
Secondary Endpoints:
• ORR, DR, and DCR according to RECIST Version 1.1 as determined by
investigator assessment
• OS
• Treatment-emergent adverse events (AEs), laboratory abnormalities, and
electrocardiogram (ECG) abnormalities
• Plasma PK parameters for rociletinib based on sparse sampling
Inclution Criteria
Inclusion Criteria
All patients must meet all of the following inclusion criteria:
1. Histologically or cytologically confirmed metastatic or unresectable locally
advanced NSCLC with radiological progression on the most recent therapy
received
2. Documented evidence of a tumor with 1 or more EGFR activating mutations
excluding exon 20 insertion
3. Disease progression confirmed by radiological assessment while receiving
treatment with single-agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or
dacomitinib). The washout period for the single agent EGFR-TKI is a minimum
of 3 days or 5 half-lives, whichever is more applicable, prior to start of treatment.
4. Multiple lines of prior treatment are permitted and there is no specified order of
treatment, but in the course of their treatment history, patients must have
received and have radiologically documented disease progression following:
− At least 1 line of prior treatment with a single-agent EGFR TKI (e.g.,
erlotinib, gefitinib, afatinib, or dacomitinib)
o If EGFR-TKI is a component of the most recent treatment line, the
washout period for the EGFR-TKI is a minimum of 3 days before
the start of rociletinib treatment
AND
− A platinum-containing doublet chemotherapy (either progressed during
therapy or completed at least 4 cycles without progression with
subsequent progression after a treatment-free interval or after a
maintenance treatment).
o If cytotoxic chemotherapy is a component of the most recent
treatment line, treatment with chemotherapy should have been
completed at least 14 days prior to start of study treatment. When an
EGFR-TKI is given in combination with platinum-containing
doublet chemotherapy, treatment with the EGFR-TKI may continue
until at least 3 days before start of treatment.
5. Have undergone a biopsy of either primary or metastatic tumor tissue within
60 days prior to start of treatment and have tissue available to send to sponsor
laboratory or are able to undergo a biopsy during screening and provide tissue to
sponsor laboratory
6. Measureable disease according to RECIST Version 1.1
7. Life expectancy of at least 3 months
8. ECOG performance status of 0 to 1
9. Age ≥ 18 years (in certain territories, the minimum age requirement may be
higher e.g., age ≥ 20 years in Japan and Taiwan, age ≥ 21 years in Singapore)
10. Patients should have recovered to National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 from any
significant chemotherapy-related toxicities
11. Adequate hematological and biological function, confirmed by the following
local laboratory values:
Bone marrow function
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109
/L
b. Platelets > 100.0 × 109
/L
c. Hemoglobin ≥ 9 g/dL (or 5.6 mmol/L)
Hepatic function
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤ 3 × upper limit of normal (ULN); if liver metastases, ≤ 5 × ULN
e. Bilirubin ≤ 2 × ULN
− Patients with documented Gilbert’s syndrome and conjugated bilirubin
within the normal range may be allowed into the study. In this event, it
will be documented that the patient was eligible based on conjugated
bilirubin levels
Renal function
f. Serum creatinine ≤ 1.5 × ULN
Electrolytes
g. Potassium and magnesium within normal range. Patients may receive
supplements to meet this requirement.
12. Written consent on an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC)-approved ICF before any study specific evaluation
All patients must meet all of the following inclusion criteria:
1. Histologically or cytologically confirmed metastatic or unresectable locally
advanced NSCLC with radiological progression on the most recent therapy
received
2. Documented evidence of a tumor with 1 or more EGFR activating mutations
excluding exon 20 insertion
3. Disease progression confirmed by radiological assessment while receiving
treatment with single-agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or
dacomitinib). The washout period for the single agent EGFR-TKI is a minimum
of 3 days or 5 half-lives, whichever is more applicable, prior to start of treatment.
4. Multiple lines of prior treatment are permitted and there is no specified order of
treatment, but in the course of their treatment history, patients must have
received and have radiologically documented disease progression following:
− At least 1 line of prior treatment with a single-agent EGFR TKI (e.g.,
erlotinib, gefitinib, afatinib, or dacomitinib)
o If EGFR-TKI is a component of the most recent treatment line, the
washout period for the EGFR-TKI is a minimum of 3 days before
the start of rociletinib treatment
AND
− A platinum-containing doublet chemotherapy (either progressed during
therapy or completed at least 4 cycles without progression with
subsequent progression after a treatment-free interval or after a
maintenance treatment).
o If cytotoxic chemotherapy is a component of the most recent
treatment line, treatment with chemotherapy should have been
completed at least 14 days prior to start of study treatment. When an
EGFR-TKI is given in combination with platinum-containing
doublet chemotherapy, treatment with the EGFR-TKI may continue
until at least 3 days before start of treatment.
5. Have undergone a biopsy of either primary or metastatic tumor tissue within
60 days prior to start of treatment and have tissue available to send to sponsor
laboratory or are able to undergo a biopsy during screening and provide tissue to
sponsor laboratory
6. Measureable disease according to RECIST Version 1.1
7. Life expectancy of at least 3 months
8. ECOG performance status of 0 to 1
9. Age ≥ 18 years (in certain territories, the minimum age requirement may be
higher e.g., age ≥ 20 years in Japan and Taiwan, age ≥ 21 years in Singapore)
10. Patients should have recovered to National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 from any
significant chemotherapy-related toxicities
11. Adequate hematological and biological function, confirmed by the following
local laboratory values:
Bone marrow function
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109
/L
b. Platelets > 100.0 × 109
/L
c. Hemoglobin ≥ 9 g/dL (or 5.6 mmol/L)
Hepatic function
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤ 3 × upper limit of normal (ULN); if liver metastases, ≤ 5 × ULN
e. Bilirubin ≤ 2 × ULN
− Patients with documented Gilbert’s syndrome and conjugated bilirubin
within the normal range may be allowed into the study. In this event, it
will be documented that the patient was eligible based on conjugated
bilirubin levels
Renal function
f. Serum creatinine ≤ 1.5 × ULN
Electrolytes
g. Potassium and magnesium within normal range. Patients may receive
supplements to meet this requirement.
12. Written consent on an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC)-approved ICF before any study specific evaluation
Exclusion Criteria
Exclusion Criteria
Any of the following criteria will exclude patients from study participation:
1. Any other malignancy associated with a high mortality risk within the next
5 years and for which the patients may be (but not necessarily) currently
receiving treatment
− Patients with a history of malignancy that has been completely treated,
with no evidence of that cancer currently, are permitted to enroll in the
trial provided all chemotherapy was completed > 6 months prior and/or
bone marrow transplant > 2 years prior
2. Known pre-existing interstitial lung disease
3. Tumor small cell transformation by local assessment, irrespective of presence of
T790M+ component
4. Patients with leptomeningeal carcinomatosis are excluded. Other central nervous
system (CNS) metastases are only permitted if treated, asymptomatic, and stable
(not requiring steroids for at least 2 weeks prior to randomization and the patient
is neurologically stable; i.e. free from new symptoms of brain metastases). If a
patient has had brain metastasis treated within the previous 8 weeks, a follow-up
scan should have been performed to confirm that treated metastasis remain
controlled without evidence of new lesions.
5. Patients who are currently receiving treatment with any medications that have
the potential to prolong the QT interval and that treatment cannot be either
discontinued or switched to a different medication (known to have no effect on
QT) before starting protocol-specified treatment (see http://crediblemeds.org/ for
a list of QT-prolonging medications)
6. Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR
with sparing of WT-EGFR including but not limited to AZD9291, HM61713,
and TAS-121
7. Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or
docetaxel unless a contraindication with respect to one of these drugs will not
affect the use of any of the others as a comparator to rociletinib
8. Any of the following cardiac abnormalities or history:
a. Clinically significant abnormal 12-lead ECG, QT interval corrected
using Fridericia’s method (QTCF) > 450 msec
b. Inability to measure QT interval on ECG
c. Personal or family history of long QT syndrome
d. Implantable pacemaker or implantable cardioverter defibrillator
e. Resting bradycardia < 55 beats/min
9. Non-study related surgical procedures ≤ 7 days prior to randomization. In all
cases, the patient must be sufficiently recovered and stable before treatment
administration.
10. Females who are pregnant or breastfeeding
11. Refusal to use adequate contraception for fertile patients (females and males)
while on treatment and for 6 months after the last dose of study treatment
(rociletinib and chemotherapy irrespective of single cytotoxic agent used)
12. Presence of any serious or unstable concomitant systemic disorder incompatible
with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness
including uncontrolled diabetes, active infection, arterial thrombosis, and
symptomatic pulmonary embolism)
13. Any other reason the investigator considers the patient should not participate in
the study
Any of the following criteria will exclude patients from study participation:
1. Any other malignancy associated with a high mortality risk within the next
5 years and for which the patients may be (but not necessarily) currently
receiving treatment
− Patients with a history of malignancy that has been completely treated,
with no evidence of that cancer currently, are permitted to enroll in the
trial provided all chemotherapy was completed > 6 months prior and/or
bone marrow transplant > 2 years prior
2. Known pre-existing interstitial lung disease
3. Tumor small cell transformation by local assessment, irrespective of presence of
T790M+ component
4. Patients with leptomeningeal carcinomatosis are excluded. Other central nervous
system (CNS) metastases are only permitted if treated, asymptomatic, and stable
(not requiring steroids for at least 2 weeks prior to randomization and the patient
is neurologically stable; i.e. free from new symptoms of brain metastases). If a
patient has had brain metastasis treated within the previous 8 weeks, a follow-up
scan should have been performed to confirm that treated metastasis remain
controlled without evidence of new lesions.
5. Patients who are currently receiving treatment with any medications that have
the potential to prolong the QT interval and that treatment cannot be either
discontinued or switched to a different medication (known to have no effect on
QT) before starting protocol-specified treatment (see http://crediblemeds.org/ for
a list of QT-prolonging medications)
6. Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR
with sparing of WT-EGFR including but not limited to AZD9291, HM61713,
and TAS-121
7. Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or
docetaxel unless a contraindication with respect to one of these drugs will not
affect the use of any of the others as a comparator to rociletinib
8. Any of the following cardiac abnormalities or history:
a. Clinically significant abnormal 12-lead ECG, QT interval corrected
using Fridericia’s method (QTCF) > 450 msec
b. Inability to measure QT interval on ECG
c. Personal or family history of long QT syndrome
d. Implantable pacemaker or implantable cardioverter defibrillator
e. Resting bradycardia < 55 beats/min
9. Non-study related surgical procedures ≤ 7 days prior to randomization. In all
cases, the patient must be sufficiently recovered and stable before treatment
administration.
10. Females who are pregnant or breastfeeding
11. Refusal to use adequate contraception for fertile patients (females and males)
while on treatment and for 6 months after the last dose of study treatment
(rociletinib and chemotherapy irrespective of single cytotoxic agent used)
12. Presence of any serious or unstable concomitant systemic disorder incompatible
with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness
including uncontrolled diabetes, active infection, arterial thrombosis, and
symptomatic pulmonary embolism)
13. Any other reason the investigator considers the patient should not participate in
the study
The Estimated Number of Participants
-
Taiwan
80 participants
-
Global
600 participants
