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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01526928
Registration number
NCT01526928
Ethics application status
Date submitted
31/01/2012
Date registered
6/02/2012
Date last updated
4/08/2020
Titles & IDs
Public title
Study to Evaluate Safety, Pharmacokinetics, and Efficacy of Rociletinib (CO-1686) in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients
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Scientific title
A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)
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Secondary ID [1]
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CO-1686-008
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Non Small Cell Lung Cancer
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Condition category
Condition code
Cancer
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Lung - Mesothelioma
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Cancer
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Lung - Non small cell
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Cancer
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Lung - Small cell
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Rociletinib
Treatment: Drugs - Rociletinib
Treatment: Drugs - Rociletinib
Treatment: Drugs - Rociletinib
Treatment: Drugs - Rociletinib
Treatment: Drugs - Rociletinib
Experimental: Rociletinib <900 mg BID FB formulation - Rociletinib free base (FB) dose \<900 mg twice a day (BID)
Experimental: Rociletinib 900 mg BID FB formulation - Rociletinib free base (FB) dose 900 mg twice a day (BID)
Experimental: Rociletinib 500 mg BID HBr formulation - Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID)
Experimental: Rociletinib 625 mg BID HBr formulation - Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID)
Experimental: Rociletinib 750 mg BID HBr formulation - Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID)
Experimental: Rociletinib 1000 mg BID HBr formulation - Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID)
Treatment: Drugs: Rociletinib
Phase 1: Rociletinib \<900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
Treatment: Drugs: Rociletinib
Phase 1: Rociletinib 900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
Treatment: Drugs: Rociletinib
Phase 1: Rociletinib 500 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 500 mg BID HBr will be administered daily
Treatment: Drugs: Rociletinib
Phase 1: Rociletinib 625 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 625 mg BID HBr will be administered daily
Treatment: Drugs: Rociletinib
Phase 1: Rociletinib 750 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 750 mg BID HBr will be administered daily
Treatment: Drugs: Rociletinib
Phase 1: Rociletinib 1000 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 1000 mg BID HBr will be administered daily
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of T790M Positive Patients With Confirmed Response Per Investigator
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Assessment method [1]
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Percentage of patients with a T790M mutation (determined by central lab) with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
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Timepoint [1]
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Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
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Primary outcome [2]
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Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment
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Assessment method [2]
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Duration of Response in patients with a T790M mutation (determined by central lab) with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from the date that any of these best responses is first recorded until the first date that progressive disease (PD) is objectively documented. For patients who continue treatment post-progression, the first date of progression was used for the analysis.
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Timepoint [2]
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Cycle 1 Day 1 to End of Treatment, up to approximately 36 months
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Primary outcome [3]
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Dose Limiting Toxicity (DLT) Incidence
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Assessment method [3]
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The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.
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Timepoint [3]
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Cycle 1 Day 1 to Cycle 1 Day 21
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Secondary outcome [1]
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Overall Survival (OS) Determined by Investigator Assessment
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Assessment method [1]
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Overall survival was calculated as 1+ the number of days from the first dose of study drug to death due to any cause. Patients without a documented date of death were censored on the date the patient was last known to be alive.
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Timepoint [1]
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Cycle 1 Day 1 to date of death, assessed up to 42 months
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Secondary outcome [2]
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Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
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Assessment method [2]
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Progression-free survival was calculated as the number of days from the date of the first dose of study drug to the date of disease progression or death due to any cause + 1. Patients without a documented event of disease progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment) or date of first dose of study drug if no tumor assessments have been performed. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
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Timepoint [2]
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Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
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Secondary outcome [3]
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PK Profile of Rociletinib - Cmax
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Assessment method [3]
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Cmax = maximum concentration following administration of rociletinib
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Timepoint [3]
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Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
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Secondary outcome [4]
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PK Profile of Rociletinib - Tmax
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Assessment method [4]
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Tmax = time to maximum concentration following administration of rociletinib
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Timepoint [4]
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Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
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Secondary outcome [5]
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PK Profile of Rociletinib - AUC 0-24
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Assessment method [5]
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AUC 0-24 = area under the curve from 0 to 24 hours
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Timepoint [5]
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Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
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Secondary outcome [6]
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PK Profile of Rociletinib - T 1/2
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Assessment method [6]
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T 1/2 = elimination half-life following administration of rociletinib
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Timepoint [6]
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Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
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Secondary outcome [7]
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Food Effect on PK of Rociletinib - Cmax
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Assessment method [7]
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Cmax = maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
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Timepoint [7]
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Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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Secondary outcome [8]
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Food Effect on PK of Rociletinib - Tmax
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Assessment method [8]
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Tmax = time to maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
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Timepoint [8]
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Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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Secondary outcome [9]
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Food Effect on PK of Rociletinib - AUC 0-24
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Assessment method [9]
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AUC 0-24 = area under the curve from 0 to 24 hours. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
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Timepoint [9]
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Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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Secondary outcome [10]
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Food Effect on PK of Rociletinib - C24
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Assessment method [10]
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C24 = rociletinib plasma concentration at 24 hours post the morning dose. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
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Timepoint [10]
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Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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Secondary outcome [11]
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Food Effect on PK of Rociletinib - T 1/2
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Assessment method [11]
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T 1/2 = elimination half-life following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
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Timepoint [11]
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Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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Secondary outcome [12]
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QTcF Values Post Baseline by Daily Dose
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Assessment method [12]
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Frequency of QT interval prolongation by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
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Timepoint [12]
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Screening to End of Treatment, up to approximately 42 months
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Secondary outcome [13]
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QTcF Value Change From Baseline
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Assessment method [13]
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QTcF value change from baseline by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
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Timepoint [13]
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Screening to End of Treatment, up to approximately 42 months
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Secondary outcome [14]
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Objective Response Rate (ORR), Duration of Response (DOR) and Progression-Free Survival (PFS) Per RECIST Version 1.1 as Determined by IRR
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Assessment method [14]
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Objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS) per RECIST Version 1.1 as determined by independent radiology review (IRR)
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Timepoint [14]
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Cycle 1 Day 1 to End of Treatment / End of Follow-up
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Eligibility
Key inclusion criteria
Inclusion Criteria -
All patients must meet the following inclusion criteria:
1. Metastatic or unresectable locally advanced NSCLC
2. Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion
3. Biopsy of either primary or metastatic tumor tissue within 60 days of dosing
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
5. Minimum age of 18 years
6. Adequate hematological and biological function
7. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation
Phase 2 Cohorts must also meet the following inclusion criteria:
* Disease progression confirmed by radiologic assessment while on treatment with EGFR- TKI Or
* Disease progression confirmed by radiologic assessment while on treatment with the first single agent EGFR TKI and
* Documented evidence of T790M mutation in EGFR following disease progression on the first single agent EGFR TKI.
* Measureable disease according to RECIST Version 1.1
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion Criteria -
Any of the following criteria will exclude patients from study participation:
1. Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene
2. Active second malignancy
3. Known pre-existing interstitial lung disease
4. Patients with Leptomeningeal carcinomatosis are excluded. Other CNS metastases are only permitted if treated, asymptomatic and stable (not requiring steroids for at least 4 weeks prior to start of study treatment).
5. Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib
6. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting rociletinib
7. Prior treatment with rociletinib or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR
8. Certain cardiac abnormalities or history
9. Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib
10. Females who are pregnant or breastfeeding
11. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib
12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
13. Any other reason the investigator considers the patient should not participate in the study
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
27/03/2012
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
27/08/2018
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Sample size
Target
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Accrual to date
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Final
612
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Chris O'Brien Lifehouse - Camperdown
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Recruitment hospital [2]
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Peter MacCallum Cancer Centre - East Melbourne
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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- East Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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United States of America
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Colorado
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District of Columbia
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Maryland
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United States of America
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Massachusetts
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Michigan
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New Jersey
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New York
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Ohio
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United States of America
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Oklahoma
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United States of America
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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France
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Provence Alpes COTE D'azur
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France
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Rhone-alpes
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France
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Caen Cedex 05
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France
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Creteil cedex
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France
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Lille
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France
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Villejuif
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Poland
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State/province [27]
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Gdansk
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Clovis Oncology, Inc.
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
Rociletinib is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.
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Trial website
https://clinicaltrials.gov/study/NCT01526928
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Trial related presentations / publications
Krug AK, Enderle D, Karlovich C, Priewasser T, Bentink S, Spiel A, Brinkmann K, Emenegger J, Grimm DG, Castellanos-Rizaldos E, Goldman JW, Sequist LV, Soria JC, Camidge DR, Gadgeel SM, Wakelee HA, Raponi M, Noerholm M, Skog J. Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma. Ann Oncol. 2018 Mar 1;29(3):700-706. doi: 10.1093/annonc/mdx765. Sequist LV, Soria JC, Goldman JW, Wakelee HA, Gadgeel SM, Varga A, Papadimitrakopoulou V, Solomon BJ, Oxnard GR, Dziadziuszko R, Aisner DL, Doebele RC, Galasso C, Garon EB, Heist RS, Logan J, Neal JW, Mendenhall MA, Nichols S, Piotrowska Z, Wozniak AJ, Raponi M, Karlovich CA, Jaw-Tsai S, Isaacson J, Despain D, Matheny SL, Rolfe L, Allen AR, Camidge DR. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1700-9. doi: 10.1056/NEJMoa1413654.
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Public notes
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Contacts
Principal investigator
Name
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Address
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Fax
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Contact person for public queries
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/28/NCT01526928/SAP_000.pdf
Study protocol
https://cdn.clinicaltrials.gov/large-docs/28/NCT01526928/Prot_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01526928
Download to PDF