Locally Advanced or Metastatic Non Small Cell Lung CancerPhase 1/2NCT01526928
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
A Phase 1/2 study testing Rociletinib in people with Locally Advanced or Metastatic Non Small Cell Lung Cancer, run by Clovis Oncology, Inc. at 49 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced or Metastatic Non Small Cell Lung Cancer
- What is being tested?
- Rociletinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 612 participants
- Where
- 49 sitesin 4 countries
- Study dates
- 27 Mar 2012to 27 Aug 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must meet the following inclusion criteria:
- Metastatic or unresectable locally advanced NSCLC
- Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion
- Biopsy of either primary or metastatic tumor tissue within 60 days of dosing
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Minimum age of 18 years
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- Adequate hematological and biological function
- 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
Who cannot join
- Any of the following criteria will exclude patients from study participation:
- Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene
- Active second malignancy
- Known pre-existing interstitial lung disease
- 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).
- Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib
Show all 14Show fewer
- 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
- Certain cardiac abnormalities or history
- Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib
- Females who are pregnant or breastfeeding
- Refusal to use adequate contraception for fertile patients (females and males) 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
Trial locations and contacts
49 sites in 4 countries.
49 sites in 4 countries
United States39 sites
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106-0995
University Cancer & Blood Center
Athens, Georgia, 30607
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
University of Maryland
Baltimore, Maryland, 21201
Mass General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Chicago Medical Center, The Duchossois Center for Advanced Medicine
Chicago, Illinois, 60637
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Ohio State University, Comprehensive Cancer Center
Columbus, Ohio, 43202
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-9179
Karmanos Cancer Care Institute
Detroit, Michigan, 48201
City of Hope National Medical Center
Duarte, California, 91010
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Compassionate Care Research Group, Inc.
Fountain Valley, California, 92708
MD Anderson Cancer Center
Houston, Texas, 77030
Monter Cancer Center
Lake Success, New York, 11042
University of Southern California, Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Samuel Oschin Cancer Center
Los Angeles, California, 90048
Sylvester Comprehensive Cancer Center/UMHC
Miami, Florida, 33136
Regional Cancer Care Associates
Morristown, New Jersey, 07962
Vanderbilt University
Nashville, Tennessee, 37235
Regional Cancer Center
New Brunswick, New Jersey, 07834
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California, Irvine
Orange, California, 92868
Florida Hospital Cancer Institute
Orlando, Florida, 32804
Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Cancer Institute (UPMC), Div. of Medical Oncology
Pittsburgh, Pennsylvania, 15232
Providence CancerCenter Oncology and Hematology Care Clinic-Eastside Portland
Portland, Oregon, 97213
University of California Davis Medical Center
Sacramento, California, 95817
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
UCLA Health System
Santa Monica, California, 90404
Swedish Cancer Institute
Seattle, Washington, 98104
University of Washington
Seattle, Washington, 98109
Stanford Cancer Institute
Stanford, California, 94305
Tulsa Cancer Institute
Tulsa, Oklahoma, 74146
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
East Valley Hematology and Oncology Medical Group, Inc.
Whittier, California, 90603
The Oncology Institute of Hope and Innovations
Whittier, California, 90603
France7 sites
Centre François Baclesse
Caen
Centre Hospitalier Intercommunal Créteil
Créteil
Centre Hospitalier Universitaire de Grenoble
Grenoble, Auvergne-Rhône-Alpes
Centre Hospitalier Régional Universitaire de Lille
Lille
Centre Léon Bérard
Lyon, Auvergne-Rhône-Alpes
Centre Antoine Lacassagne
Nice, Provence-Alpes-Côte d'Azur Region, 06189
Institut Gustave Roussy
Villejuif, 94805
Australia2 sites
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Peter MacCallum Cancer Centre
East Melbourne
About this study
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)
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.
Read the detailed description
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. There are currently no approved therapies for patients who progress on TKIs. Rociletinib may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs.
This is a two-part, open-label study of oral rociletinib administered daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib.
This study will include 2 parts:
Phase 1: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22
Phase 2: Evaluation of activity and safety in patients with the T790M EGFR mutation who have:
Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR directed therapy received and also had no more than one previous line of chemotherapy or Cohort C - Patients with discordance between local (T790M positive) and central (T790M negative) T790M results, or had no central test result due to inadequacy of the tissue specimen and known to be T790M positive by local test
- Being tested
- Rociletinib
- Keywords
- cancer, metastatic, locally advanced, lung, non-small cell lung cancer, NSCLC, epidermal growth factor receptor, EGFR, T790M, CO-1686, unresectable, recurrent, EGFR-directed therapy, irreversible EGFR inhibitor, TIGER, Rociletinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms, Neoplasm Metastasis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RociletinibDrug
Also called CO-1686
Phase 1: Rociletinib <900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
RociletinibDrug
Also called CO-1686
Phase 1: Rociletinib 900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
RociletinibDrug
Also called CO-1686
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
RociletinibDrug
Also called CO-1686
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
RociletinibDrug
Also called CO-1686
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
RociletinibDrug
Also called CO-1686
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
| Study group | Role | What they receive |
|---|---|---|
| Rociletinib <900 mg BID FB formulation | Experimental | Rociletinib free base (FB) dose <900 mg twice a day (BID) Receives: Drug: Rociletinib |
| Rociletinib 900 mg BID FB formulation | Experimental | Rociletinib free base (FB) dose 900 mg twice a day (BID) Receives: Drug: Rociletinib |
| Rociletinib 500 mg BID HBr formulation | Experimental | Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID) Receives: Drug: Rociletinib |
| Rociletinib 625 mg BID HBr formulation | Experimental | Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID) Receives: Drug: Rociletinib |
| Rociletinib 750 mg BID HBr formulation | Experimental | Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID) Receives: Drug: Rociletinib |
| Rociletinib 1000 mg BID HBr formulation | Experimental | Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID) Receives: Drug: Rociletinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
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.
Measured: Cycle 1 Day 1 to End of Treatment, up to approximately 36 months
Dose Limiting Toxicity (DLT) Incidence
The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.
Measured: Cycle 1 Day 1 to Cycle 1 Day 21
Secondary outcomes (14)
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.
Measured: Cycle 1 Day 1 to date of death, assessed up to 42 months
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.
Measured: Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
PK Profile of Rociletinib - Cmax
Cmax = maximum concentration following administration of rociletinib
Measured: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - Tmax
Tmax = time to maximum concentration following administration of rociletinib
Measured: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - AUC 0-24
AUC 0-24 = area under the curve from 0 to 24 hours
Measured: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - T 1/2
T 1/2 = elimination half-life following administration of rociletinib
Measured: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
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.
Measured: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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.
Measured: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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.
Measured: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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.
Measured: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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.
Measured: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
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.
Measured: Screening to End of Treatment, up to approximately 42 months
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.
Measured: Screening to End of Treatment, up to approximately 42 months
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)
Measured: Cycle 1 Day 1 to End of Treatment / End of Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2012 (estimated)
- Study start27 Mar 2012
- Primary completion3 Jul 2018
- Study completion27 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced or Metastatic Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 612 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clovis Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01526928
- Sponsor's protocol ID
- CO-1686-008
- Status last verified
- Jul 2020
- First submitted
- 31 Jan 2012
- Last updated
- 4 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 29216356Sequist 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.
PubMed 25923550
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01526928
- Acronym / sponsor ID
- CO-1686-008
- Keywords
- cancer, metastatic, locally advanced, lung, non-small cell lung cancer, NSCLC, epidermal growth factor receptor, EGFR
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 612 participants (actual)
- Lead sponsor
- Clovis Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Mar 2012 (actual)
- Primary completion
- 3 Jul 2018 (actual)
- Study completion
- 27 Aug 2018 (actual)
- First posted
- 6 Feb 2012 (estimated)
- Results
- Posted 6 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. There are currently no approved therapies for patients who progress on TKIs. Rociletinib may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs.
This is a two-part, open-label study of oral rociletinib administered daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib.
This study will include 2 parts:
Phase 1: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22
Phase 2: Evaluation of activity and safety in patients with the T790M EGFR mutation who have:
Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR directed therapy received and also had no more than one previous line of chemotherapy or Cohort C - Patients with discordance between local (T790M positive) and central (T790M negative) T790M results, or had no central test result due to inadequacy of the tissue specimen and known to be T790M positive by local test
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Rociletinib <900 mg BID FB formulation | Experimental | Drug: RociletinibRociletinib free base (FB) dose <900 mg twice a day (BID) |
| Rociletinib 900 mg BID FB formulation | Experimental | Drug: RociletinibRociletinib free base (FB) dose 900 mg twice a day (BID) |
| Rociletinib 500 mg BID HBr formulation | Experimental | Drug: RociletinibRociletinib hydrobromide (HBr) dose 500 mg twice a day (BID) |
| Rociletinib 625 mg BID HBr formulation | Experimental | Drug: RociletinibRociletinib hydrobromide (HBr) dose 625 mg twice a day (BID) |
| Rociletinib 750 mg BID HBr formulation | Experimental | Drug: RociletinibRociletinib hydrobromide (HBr) dose 750 mg twice a day (BID) |
| Rociletinib 1000 mg BID HBr formulation | Experimental | Drug: RociletinibRociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Metastatic or unresectable locally advanced NSCLC
- Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion
- Biopsy of either primary or metastatic tumor tissue within 60 days of dosing
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Minimum age of 18 years
Key exclusion criteria (14 listed)
- Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene
- Active second malignancy
- Known pre-existing interstitial lung disease
- 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).
- Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RociletinibAlso: CO-1686Phase 1: Rociletinib <900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles | Drug | Rociletinib <900 mg BID FB formulation |
| RociletinibAlso: CO-1686Phase 1: Rociletinib 900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles | Drug | Rociletinib 900 mg BID FB formulation |
| RociletinibAlso: CO-1686Phase 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 | Drug | Rociletinib 500 mg BID HBr formulation |
| RociletinibAlso: CO-1686Phase 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 | Drug | Rociletinib 625 mg BID HBr formulation |
| RociletinibAlso: CO-1686Phase 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 | Drug | Rociletinib 750 mg BID HBr formulation |
| RociletinibAlso: CO-1686Phase 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 | Drug | Rociletinib 1000 mg BID HBr formulation |
Primary outcome
Percentage of T790M Positive Patients With Confirmed Response Per Investigator
Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
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.
Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment
Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 36 months
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.
Dose Limiting Toxicity (DLT) Incidence
Time frame: Cycle 1 Day 1 to Cycle 1 Day 21
The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.
14 secondary outcomes
Overall Survival (OS) Determined by Investigator Assessment
Time frame: Cycle 1 Day 1 to date of death, assessed up to 42 months
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
PK Profile of Rociletinib - Cmax
Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - Tmax
Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - AUC 0-24
Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - T 1/2
Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
Food Effect on PK of Rociletinib - Cmax
Time frame: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - Tmax
Time frame: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - AUC 0-24
Time frame: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - C24
Time frame: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - T 1/2
Time frame: Day -7 prior to Cycle 1 Day 1, or approximately 7 days
QTcF Values Post Baseline by Daily Dose
Time frame: Screening to End of Treatment, up to approximately 42 months
QTcF Value Change From Baseline
Time frame: Screening to End of Treatment, up to approximately 42 months
Objective Response Rate (ORR), Duration of Response (DOR) and Progression-Free Survival (PFS) Per RECIST Version 1.1 as Determined by IRR
Time frame: Cycle 1 Day 1 to End of Treatment / End of Follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29216356Krug 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.
- Derived from this study: PubMed 25923550Sequist 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
49 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rociletinib in people with Locally Advanced or Metastatic Non Small Cell Lung Cancer, run by Clovis Oncology, Inc. at 49 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, France, Australia, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of T790M Positive Patients With Confirmed Response Per Investigator (time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 42 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01526928, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2020.