Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer

Phase 2TerminatedNCT02147990

Clovis Oncology, Inc.318 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

318

Conditions

Non-small Cell Lung Cancer

Interventions

RociletinibDRUG

Rociletinib will be administered to patients orally

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria * Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC * Documented evidence of a tumor with 1 or more EGFR mutations excluding exon 20 insertion * Disease progression confirmed by radiologic assessment while receiving treatment with the first single agent EGFR-TKI * EGFR TKI treatment discontinued less than or equal to 30 days prior to planned initiation of rociletinib * The washout period for an EGFR inhibitor is a minimum of 3 days * No intervening treatment between cessation of single agent EGFR TKI and planned initiation of rociletinib * Previous treatment with less than or equal to 1 prior chemotherapy (excluding prior neo-adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent) * Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less * Central laboratory confirmation of the presence of the T790M mutation in tumor tissue in Cohort A and the presence or absence of the T790M mutation in tumor tissue in Cohort B. Centrally indeterminate, unknown or invalid specimens are not acceptable. Biopsy material obtained from either primary or metastatic tumor tissue and sent to the central laboratory must be within 60 prior to dosing study drug but following disease progression on the first EGFR TKI * Measurable disease according to RECIST Version 1.1 * Life expectancy of at least 3 months * ECOG performance status of 0 to 1 * Minimum Age 18 years (in certain territories, the minimum age requirement may be higher eg age 20 years in Japan and Taiwan) * Adequate hematological and biological function, confirmed by defined laboratory values * Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study specific evaluation Exclusion Criteria * Documented evidence of an exon 20 insertion activating mutation in the EGFR gene * Active second malignancy i.e. patient known to have potentially fatal cancer present for which he/she 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 enrol in the trial provided all chemotherapy was completed greater than 6 months prior and/or bone marrow transplant greater than 2 years prior * Known pre-existing interstitial lung disease * Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroid for at least 4 weeks prior to the start of study treatment). Cohort B only: Patients with CNS metastases or leptomeningeal carcinomatosis are excluded. * Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib * 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 * Prior treatment with rociletinib, or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR * Any of the following cardiac abnormalities or history * Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) greater than 450 msec * Inability to measure QT interval on ECG * Personal or family history of long QT syndrome * Implantable pacemaker or implantable cardioverter defibrillator * Resting bradycardia less than 55 beats/min * Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib. In all cases, the patient must be sufficiently recovered and stable before treatment administration * Females who are pregnant or breastfeeding * Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 12 weeks after the last dose of rociletinib * Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study * Any other reason the investigator considers the patient should not participate in the study

Locations (91)

Outcomes

Primary Outcomes

Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment

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.

Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 57 months.

Secondary Outcomes

Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment

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.

Time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months

Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment

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.

Data from ClinicalTrials.gov

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Alhambra, California, United States

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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

...and 81 more locations

Time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months

Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment

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.

Time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months

Overall Survival (OS) Determined by Investigator Assessment

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.

Time frame: Cycle 1 Day 1 to date of death, assessed up to 57 months

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

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.