Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer
- Registration Number
- NCT02147990
- Lead Sponsor
- Clovis Oncology, Inc.
- Brief Summary
The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib. The trial is open-ended, which means patients will continue to take rociletinib until the study doctor determines it is no longer beneficial for them.
- Detailed Description
This is a Phase 2, single arm, open-label, dual cohort, multicenter study evaluating the safety and efficacy of rociletinib administered orally to patients with previously treated mutant EGFR NSCLC.
Patients will be enrolled into 2 cohorts. Cohort A will enroll approximately 125 eligible patients who are centrally confirmed T790M-positive. Cohort B will be a continuation of the study and will enroll up to approximately 100 eligible patients who will be either centrally confirmed T790M-positive or T790M-negative.
All patients (for Cohort A and B) should have experienced disease progression while on treatment with the first single-agent EGFR-directed TKI (EGFR-TKI) for advanced/metastatic NSCLC. One line of chemotherapy prior to the EGFR-TKI treatment is permissible.
The study (Cohorts A and B) will consist of a screening phase to establish study eligibility and document baseline measurements, an open-label treatment phase, in which the patient will receive rociletinib to ascertain safety and efficacy until disease progression as defined by RECIST Version 1.1, clinical tumor progression, or unacceptable toxicity as assessed by the investigator. For patients with clinical progression, radiographic assessment should be performed to document evidence of radiographic progression.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 318
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rociletinib Mono-Therapy, T790M +ve (625mg BID) Rociletinib Starting dose of 625mg rociletinib, taken orally twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days. Rociletinib Mono-Therapy, T790M -ve (500mg BID) Rociletinib Starting dose of 500mg rociletinib, taken twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days. Rociletinib Mono-Therapy, T790M +ve (500mg BID) Rociletinib Starting dose of 500mg rociletinib, taken orally twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment Cycle 1 Day 1 to End of Treatment, up to approximately 57 months. ORR is defined as the percentage of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression. For patients who continued treatment post-progression, the first date of progression was used for the analysis. 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months DOR 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.
Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months DCR is defined as the percentage of patients who have achieved CR, PR, and SD lasting at least 12 weeks. 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. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months PFS was calculated as 1+ the number of days from the first dose of study drug to documented radiographic progression or death due to any cause, whichever occurs first. Patients without a documented event of radiographic 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 were performed. For patients who continued treatment post-progression, the first date of progression was used for the analysis of PFS. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.
Overall Survival (OS) Determined by Investigator Assessment Cycle 1 Day 1 to date of death, assessed up to 57 months OS 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 will be censored on the date the patient was last known to be alive.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) Baseline (Day 0), Months 5, 10 and EOT Dermatology Life Quality Index (DLQI) score is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which the participant's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much (score of 3), a lot, a little, or not at all (score of 0). The DLQI score ranges from 0 (best) to 30 (worst); the higher the score, the more quality of life is impaired.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale Baseline (Day 0), Months 5, 10 and EOT EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Population PK (POPPK) and Exposure-Response (ER) Analysis of Rociletinib Every 4 weeks for approximately 6 months (Day 1 of Cycles 2 to 7 inclusive) Sparse blood sampling for POPPK and ER analyses in all patients treated with rociletinib.
Trial Locations
- Locations (88)
UCLA Medical Center
🇺🇸Alhambra, California, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Saint Jude Heritage Healthcare
🇺🇸Fullerton, California, United States
University of California San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Northridge Hospital Medical Center
🇺🇸Northridge, California, United States
Cancer Care Associates
🇺🇸Redondo Beach, California, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Coastal Integrative Cancer Care
🇺🇸San Luis Obispo, California, United States
Saint Mary's Regional Cancer Center
🇺🇸Grand Junction, Colorado, United States
Scroll for more (78 remaining)UCLA Medical Center🇺🇸Alhambra, California, United States