Carcinoma, Non-Small-Cell LungPhase 2NCT02705339
Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)
A Phase 2 study testing Rociletinib, Biopsy and Blood draw in people with Carcinoma, Non-Small-Cell Lung and Non-Small Cell Lung Cancer, run by Washington University School of Medicine.
Trial summary
Though patients whose tumors harbor EGFR T790M mutation appear to benefit from rociletinib, there is a need to understand the molecular mechanisms that lead to primary and acquired resistance to rociletinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer
- What is being tested?
- Rociletinib, Biopsy and Blood draw
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- May 2016to Apr 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Histologically or cytologically confirmed metastatic stage IIIB/IV lung adenocarcinoma with known activating mutations in the EGFR TK domain (including exon 19 deletion and L858R)
- Prior EGFR TKI therapy with progression, and documented EGFR T790M mutation on tumor biopsy; however, this need not be only second line
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- At least 18 years of age.
- ECOG performance status ≤ 2
- Normal bone marrow and organ function as defined below:
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- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin ≥ 9.0 g/dL
- INR ≤ 2.0
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Potassium within institutional limits (supplementation allowed)
- Magnesium within normal limits (supplementation allowed)
- Tumor tissue available and deemed adequate for genomic studies.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Currently receiving any other investigational agents.
- Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
- Symptomatic, untreated or unstable central nervous system or leptomeningeal metastases. (Patients with treated and stable brain metastases (confirmed by 2 scans at least 4 weeks apart), with no evidence of cavitation or hemorrhage in the brain lesion are eligible provided that they are asymptomatic and do not require corticosteroids.)
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to rociletinib or other agents used in the study.
- Currently receiving treatment with any medication that has the potential to prolong the QT interval and the treatment cannot be discontinued or switched to a different medication.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the previous 3 months, coronary angioplasty or stenting or bypass grafting within the past 6 months, cardiac ventricular arrhythmias requiring medication, any history of 2nd or 3rd degree atrioventricular conduction defects, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of interstitial lung disease.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Class II to IV heart failure as defined by the New York Heart Association functional classification system. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable medial regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate, to be eligible.
- Any of the following cardiac abnormalities or history:
- Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) > 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 < 55 beats/min
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
- Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with rociletinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Active hepatitis B virus (HBV) defined by positive hepatitis B surface antigen (HBsAg) test at screening. Patients with past or resolved HBV infection (defined by a negative HBsAg test and a positive anti-hepatitis B core antigen (anti-HBc) antibody test) are eligible. HBV DNA must be obtained in these patients prior to first day of study treatment.
- Active hepatitis C virus (HCV). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
- Active tuberculosis.
- Presence of active GI disease (including GI bleeding or ulceration) or other condition that could affect GI absorption) (e.g. malabsorption syndrome, history of biliary tract disease).
About this study
Official title: Genomic Landscape of EGFR Mutant NSCLC Prior to Rociletinib and at the Time of Disease Progression Following Rociletinib
Though patients whose tumors harbor EGFR T790M mutation appear to benefit from rociletinib, there is a need to understand the molecular mechanisms that lead to primary and acquired resistance to rociletinib. The investigators propose to conduct a clinical trial of rociletinib of patients with EGFR-mutant NSCLC with activating EGFR mutations (including exon 19 deletion or L858R mutation), with or without EGFR T790M mutation. In these patients, pre-treatment and post-progression biopsy specimens will be subjected to genomic analysis to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance.
- Being tested
- Rociletinib, Biopsy, Blood draw
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RociletinibDrug
Also called CO-1686
BiopsyProcedure or surgery
Standard of care biopsies will be taken at diagnosis and at the time of disease progression
Blood drawProcedure or surgery
-Approximately 4 teaspoons of blood will be drawn before treatment begins and at the time of disease progression to look at cell-free DNA
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Rociletinib | Experimental | * Rociletinib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg twice per day during each 28-day cycle.
* After completion of cycle 1, patients who tolerate the 500 mg twice per day dose without significant adverse effect may increase dosing to 625 mg twice per day at the discretion of the investigator Receives: Drug: Rociletinib; Procedure: Biopsy; Procedure: Blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Somatic genetic changes in the tumor associated with disease progression
-The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with rociletinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germ line).
Measured: Until the time of disease progression (estimated median of 3 months)
Secondary outcomes (4)
Overall response rate (ORR)
- ORR: Percentage of patients experiencing complete response or partial response
- Complete Response (CR): Disappearance of all target lesions and non-target lesions.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Until the time of disease progression (estimated median of 3 months)
Overall survival (OS)
Measured: Until death (estimated median of 8 months)
Progression-free survival (PFS)
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Measured: Until the time of progression (estimated median of 3 months)
Duration of treatment
Measured: Until the time of removal from study (estimated median of 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2016 (estimated)
- Study startMay 2016
- Primary completionNov 2019 (estimated)
- Study completionApr 2020 (estimated)
Why it stopped: Clovis Oncology discontinued rociletinib.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- Saiama Waqar, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02705339
- Sponsor's protocol ID
- 201604010
- Status last verified
- May 2016
- First submitted
- 12 Jan 2016
- Last updated
- 17 May 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genomic Landscape of EGFR Mutant NSCLC Prior to Rociletinib and at the Time of Disease Progression Following Rociletinib
- ClinicalTrials.gov ID
- NCT02705339
- Acronym / sponsor ID
- 201604010
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Clovis Oncology discontinued rociletinib.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Study start
- May 2016
- Primary completion
- Nov 2019 (estimated)
- Study completion
- Apr 2020 (estimated)
- First posted
- 10 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Though patients whose tumors harbor EGFR T790M mutation appear to benefit from rociletinib, there is a need to understand the molecular mechanisms that lead to primary and acquired resistance to rociletinib. The investigators propose to conduct a clinical trial of rociletinib of patients with EGFR-mutant NSCLC with activating EGFR mutations (including exon 19 deletion or L858R mutation), with or without EGFR T790M mutation. In these patients, pre-treatment and post-progression biopsy specimens will be subjected to genomic analysis to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Rociletinib | Experimental | Drug: Rociletinib, Procedure: Biopsy, Procedure: Blood draw* Rociletinib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg twice per day during each 28-day cycle. * After completion of cycle 1, patients who tolerate the 500 mg twice per day dose without significant adverse effect may increase dosing to 625 mg twice per day at the discretion of the investigator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically or cytologically confirmed metastatic stage IIIB/IV lung adenocarcinoma with known activating mutations in the EGFR TK domain (including exon 19 deletion and L858R)
- Prior EGFR TKI therapy with progression, and documented EGFR T790M mutation on tumor biopsy; however, this need not be only second line
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- At least 18 years of age.
- ECOG performance status ≤ 2
Key exclusion criteria (22 listed)
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Currently receiving any other investigational agents.
- Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
- Symptomatic, untreated or unstable central nervous system or leptomeningeal metastases. (Patients with treated and stable brain metastases (confirmed by 2 scans at least 4 weeks apart), with no evidence of cavitation or hemorrhage in the brain lesion are eligible provided that they are asymptomatic and do not require corticosteroids.)
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to rociletinib or other agents used in the study.
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-1686 | Drug | Arm 1: Rociletinib |
| BiopsyStandard of care biopsies will be taken at diagnosis and at the time of disease progression | Procedure or surgery | Arm 1: Rociletinib |
| Blood draw-Approximately 4 teaspoons of blood will be drawn before treatment begins and at the time of disease progression to look at cell-free DNA | Procedure or surgery | Arm 1: Rociletinib |
Primary outcome
Somatic genetic changes in the tumor associated with disease progression
Time frame: Until the time of disease progression (estimated median of 3 months)
-The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with rociletinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germ line).
4 secondary outcomes
Overall response rate (ORR)
Time frame: Until the time of disease progression (estimated median of 3 months)
Overall survival (OS)
Time frame: Until death (estimated median of 8 months)
Progression-free survival (PFS)
Time frame: Until the time of progression (estimated median of 3 months)
Duration of treatment
Time frame: Until the time of removal from study (estimated median of 3 months)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2016.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Saiama Waqar, M.D. principal investigator
Washington University School of Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rociletinib, Biopsy and Blood draw in people with Carcinoma, Non-Small-Cell Lung and Non-Small Cell Lung Cancer, run by Washington University School of Medicine.
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 19 inclusion and 22 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: withdrawn, as of the sponsor's last update on 17 May 2016. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Somatic genetic changes in the tumor associated with disease progression (time frame: Until the time of disease progression (estimated median of 3 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 May 2016.