Non-small cell lungcancer
Conditions
Interventions
Patients will be randomized 1:1:1 to receive either rociletinib 500 mg BID,
rociletinib 625 mg BID, or single-agent cytotoxic chemotherapy (investigator
choice of pemetrexed, gemcitabine, docetaxel,
choice of
chemotherapy agent must be specified before randomization).
Rociletinib
Daily oral rociletinib at either 500 mg BID or 625 mg BID with 8 oz (240 mL) of
water and with a meal or within 30
ie,
dosing will be on Days 1, 8, and 15 of each 21 day cycle.
Paclitaxel
80 mg/m2 paclitaxel given intravenously as a 1 hour infusion, on a weekly basis
as part of a continuous 21 day cycle
ie, dosing will be on Days 1, 8, and 15
of each 21-day cycle.
Non-Small Cell Lung Cancer
Oral CO-1686
Sponsors
Clovis Oncology, Inc.
Eligibility
Age
18 Years to 64 Years
Inclusion 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 (eg, erlotinib, gefitinib, afatinib, or dacomitinib) or EGFR TKI in combination with other targeted therapy (eg, bevacizumab, immunotherpay). The washout period for the single agent EGFR-TKI and combination targeted therapy 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 (eg, erlotinib, gefitinib, afatinib, or dacomitinib) or EGFR TKI in combination with other targeted therapy (eg, bevacizumab, immunotherapy) 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 study drug 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 sent to the central laboratory prior to randomization 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 eg, 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 = 1.5 × 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) = 45 mL/min Electrolytes g. Potassium and magnesium within norma
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-positive 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; ie, free from new symptoms of brain metastases). If a patient has had brain metastasis treated within the previous 8 weeks, a follow-up scan must 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-positive mutant EGFR with sparing of WT EGFR including but not limited to osimertinib, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: • PFS according to RECIST Version 1.1 as determined by investigator assessment (invPFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: • ORR and DR 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 Exploratory Endpoints • DCR according to RECIST version 1.1 as determined by investigator assessment • Time-to-treatment failure • OS, ORR, PFS, DR, and DCR in patients who cross over to receive rociletinib and in patients who continue to receive rociletinib beyond progression • Change from baseline in PROs using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C30), the EORTC Quality of Life Questionnaire Lung Cancer module (EORTC QLQ LC13) and in the EQ-5D • Change from baseline in mutant EGFR levels in ctDNA obtained from plasma and urine • OS, ORR, PFS, DR, and DCR based on plasma and urine EGFR mutation test results • Positive and negative percent agreement between blood, urine and tissue results for T790M • Identify biomarkers associated with response or resistance to rociletinib | — |
Countries
Australia, France, Germany, Italy, Korea (the Republic of), Netherlands, Spain, Taiwan (Province of China), United Kingdom, United States of America
Outcome results
None listed