Locally Advanced or Metastatic Non Small Cell Lung Cancer Clinical Trial
Official 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)
| Verified date | July 2020 |
| Source | Clovis Oncology, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 612 |
| Est. completion date | August 27, 2018 |
| Est. primary completion date | July 3, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Chris O'Brien Lifehouse | Camperdown | New South Wales |
| Australia | Peter MacCallum Cancer Centre | East Melbourne | |
| France | Centre François Baclesse | Caen Cedex 05 | |
| France | Centre Hospitalier Intercommunal Créteil | Creteil cedex | |
| France | Centre Hospitalier Universitaire de Grenoble | Grenoble Cedex 9 | Rhone-alpes |
| France | Centre Hospitalier Régional Universitaire de Lille | Lille | |
| France | Centre Léon Bérard | Lyon Cedex 04 | Rhone-alpes |
| France | Centre Antoine Lacassagne | Nice Cedex 2 | Provence Alpes COTE D'azur |
| France | Institut Gustave Roussy | Villejuif | |
| Poland | Med University Gdansk | Gdansk | |
| United States | Saint Joseph Mercy Hospital | Ann Arbor | Michigan |
| United States | University Cancer & Blood Center | Athens | Georgia |
| United States | University of Colorado Anschutz Medical Campus | Aurora | Colorado |
| United States | University of Maryland | Baltimore | Maryland |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Mass General Hospital | Boston | Massachusetts |
| United States | Roswell Park Cancer Institute | Buffalo | New York |
| United States | University of Chicago Medical Center, The Duchossois Center for Advanced Medicine | Chicago | Illinois |
| United States | University of Cincinnati Medical Center | Cincinnati | Ohio |
| United States | Ohio State University, Comprehensive Cancer Center | Columbus | Ohio |
| United States | University of Texas Southwestern Medical Center | Dallas | Texas |
| United States | Karmanos Cancer Care Institute | Detroit | Michigan |
| United States | City of Hope National Medical Center | Duarte | California |
| United States | Virginia Cancer Specialists, PC | Fairfax | Virginia |
| United States | Compassionate Care Research Group, Inc. | Fountain Valley | California |
| United States | MD Anderson Cancer Center | Houston | Texas |
| United States | Monter Cancer Center | Lake Success | New York |
| United States | Samuel Oschin Cancer Center | Los Angeles | California |
| United States | University of Southern California, Norris Comprehensive Cancer Center | Los Angeles | California |
| United States | Sylvester Comprehensive Cancer Center/UMHC | Miami | Florida |
| United States | Regional Cancer Care Associates | Morristown | New Jersey |
| United States | Vanderbilt University | Nashville | Tennessee |
| United States | Regional Cancer Center | New Brunswick | New Jersey |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | University of California, Irvine | Orange | California |
| United States | Florida Hospital Cancer Institute | Orlando | Florida |
| United States | Perelman Center for Advanced Medicine | Philadelphia | Pennsylvania |
| United States | University of Pittsburgh Cancer Institute (UPMC), Div. of Medical Oncology | Pittsburgh | Pennsylvania |
| United States | Providence CancerCenter Oncology and Hematology Care Clinic-Eastside Portland | Portland | Oregon |
| United States | University of California Davis Medical Center | Sacramento | California |
| United States | Huntsman Cancer Institute | Salt Lake City | Utah |
| United States | UCLA Health System | Santa Monica | California |
| United States | Swedish Cancer Institute | Seattle | Washington |
| United States | University of Washington | Seattle | Washington |
| United States | Stanford Cancer Institute | Stanford | California |
| United States | Tulsa Cancer Institute | Tulsa | Oklahoma |
| United States | Georgetown University Hospital | Washington | District of Columbia |
| United States | East Valley Hematology and Oncology Medical Group, Inc. | Whittier | California |
| United States | The Oncology Institute of Hope and Innovations | Whittier | California |
| Lead Sponsor | Collaborator |
|---|---|
| Clovis Oncology, Inc. |
United States, Australia, France, Poland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of T790M Positive Patients With Confirmed Response Per Investigator | 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. | Cycle 1 Day 1 to End of Treatment, up to approximately 42 months | |
| Primary | Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment | 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. | Cycle 1 Day 1 to End of Treatment, up to approximately 36 months | |
| Primary | Dose Limiting Toxicity (DLT) Incidence | The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug. | Cycle 1 Day 1 to Cycle 1 Day 21 | |
| Secondary | Overall Survival (OS) Determined by Investigator Assessment | 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. | Cycle 1 Day 1 to date of death, assessed up to 42 months | |
| Secondary | Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS) | 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. | Cycle 1 Day 1 to End of Treatment, up to approximately 42 months | |
| Secondary | PK Profile of Rociletinib - Cmax | Cmax = maximum concentration following administration of rociletinib | Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days | |
| Secondary | PK Profile of Rociletinib - Tmax | Tmax = time to maximum concentration following administration of rociletinib | Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days | |
| Secondary | PK Profile of Rociletinib - AUC 0-24 | AUC 0-24 = area under the curve from 0 to 24 hours | Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days | |
| Secondary | PK Profile of Rociletinib - T 1/2 | T 1/2 = elimination half-life following administration of rociletinib | Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days | |
| Secondary | Food Effect on PK of Rociletinib - Cmax | 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. | Day -7 prior to Cycle 1 Day 1, or approximately 7 days | |
| Secondary | Food Effect on PK of Rociletinib - Tmax | 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. | Day -7 prior to Cycle 1 Day 1, or approximately 7 days | |
| Secondary | Food Effect on PK of Rociletinib - AUC 0-24 | 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. | Day -7 prior to Cycle 1 Day 1, or approximately 7 days | |
| Secondary | Food Effect on PK of Rociletinib - C24 | 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. | Day -7 prior to Cycle 1 Day 1, or approximately 7 days | |
| Secondary | Food Effect on PK of Rociletinib - T 1/2 | 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. | Day -7 prior to Cycle 1 Day 1, or approximately 7 days | |
| Secondary | QTcF Values Post Baseline by Daily Dose | 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. | Screening to End of Treatment, up to approximately 42 months | |
| Secondary | QTcF Value Change From Baseline | 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. | Screening to End of Treatment, up to approximately 42 months | |
| Secondary | Objective Response Rate (ORR), Duration of Response (DOR) and Progression-Free Survival (PFS) Per RECIST Version 1.1 as Determined by IRR | 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) | Cycle 1 Day 1 to End of Treatment / End of Follow-up |