- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT02374645
A Phase I Study of Safety and Pharmacokinetics of Volitinib in Combination With Gefitinib in EGFR(+) NSCLC
A Phase Ib, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumour Activity of Volitinib in Combination With Gefitinib in Patients With Epidermal Growth Factor Receptor-mutated Non-small Cell Lung Cancer Who Have Progressed on Epidermal Growth Factor Receptor Inhibitor Treatment
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
A total of 53 patients will be enrolled in the safety run-in and expansion phases:
- Safety run-in phase - patients with EGFR mutation-positive (EGFRm+), locally advanced or metastatic non-small cell lung cancer (NSCLC), who have progressed on previous EGFT TKI treatment.In the safety run-in phase of the study, the sample size may vary, depending on the number of dose levels evaluated and the number of Dose Limiting Toxicities (DLTs) observed in each cohort.
- Expansion phase - patients who are EGFRm+ and cMet-positive with locally advanced or metastatic NSCLC, who have progressed on previous EGFR-TKI treatment.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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Guangzhou, Cina, 510080
- Guangdong General Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Provision of informed consent prior to any study specific procedures. If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study there will be no penalty or loss of benefit to the patient and he or she will not be excluded from other aspects of the study.
- Male or female aged at least 18 years and older.
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC patients who are harbouring an EGFR mutation known to be associated with EGFR-TKI sensitivity (including exon 19 deletion, L858R, L861Q, G719X). Local test for EGFR mutation is acceptable. In the expansion phase, patients must have a positive cMet test by a central laboratory. Safety run-in phase: EGFR mutation positive. A local EGFR test result is acceptable Expansion phase: EGFR mutation positive and cMet-positive. cMet test is performed by a central lab.
- Radiological documentation of disease progression while on a previous continuous treatment with EGFR-TKI eg, gefitinib or erlotinib. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study. The patients must have been treated with an EGFR-TKI with objective clinical benefit (CR/PR) or SD for 3 months, and who have subsequently shown radiological progression on treatment. In addition, other lines of therapy may have been given.
- At least 1 lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
Women should agree to use adequate contraceptive measures (as defined in section 5.1), should not be breast feeding, and must have a negative pregnancy test prior to start of dosing or if of child-bearing potential or of non-child- bearing potential must have evidence of this by fulfilling 1 of the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
- Women under 50 years of age would be considered postmenopausal if they have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution.
- Sexually active male patients should be willing to use barrier contraception; ie, condoms.
- For inclusion in the genetic research, patients must provide informed consent for genetic research.
Exclusion Criteria:
Intervention with any of the following:
- Treatment with an EGFR-TKI within approximately 5x half-life (eg, within 8 days for erlotinib, gefitinib or afatanib, within 10 days for dacomitinib) of the first dose of study treatment
- Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
- Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of AZD6094, medications known to be strong inhibitors of CYP1A2 (Appendix E)
- Prior or current treatment with AZD6094 or another cMet inhibitor (eg, foretinib, crizotinib, cabozantinib, onartuzumab)
- Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
- Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed ≥4 weeks of the first dose of study treatment.
- Major surgical procedure, (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study
- With the exception of alopecia and CTCAE Grade 2, prior chemotherapy-related neuropathy, any unresolved toxicities from prior therapy and/or pre-study biopsies greater than CTCAE Grade 1 at the time of starting study treatment
- Have non-measurable disease at baseline per RECIST v1.1. To ensure that the patient will be able to complete the evaluable period of the study and the assessment of progression can be performed according to the RECIST v1.1 criteria and the relevant treatment decisions applied OR can be summarised for patients with measurable disease at baseline
- Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- Current leptomeningeal metastases or spinal cord compression. Brain metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 4 weeks prior to start of study treatment).
- Patients with known tumour thrombus or deep vein thrombosis are eligible if stable on low molecular weight heparin for ≥4 weeks.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol; including evidence of active infection including hepatitis B (HBV) surface antigen, hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
- Any serious uncontrolled medical disorder or active infection that would impair the patient's ability to receive IP, such as conditions associated with frequent diarrhoea.
Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec obtained from triplicate ECGs
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG; eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval- Inadequately controlled hypertension (ie, systolic blood pressure (BP) >160 mmHg or diastolic BP >100 mmHg (patients with values above these levels must have their BP controlled with medication prior to starting treatment).
- Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
- Symptomatic heart failure - New York Heart Association (NYHA) Grade II-IV
- Unstable angina pectoris
- Acute myocardial infarction
- Uncontrolled angina (Canadian Cardiovascular Society Grade II-IV despite medical therapy)
- Stroke or transient ischemic attack in the last 6 months
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- Absolute neutrophil count <1.5x109/L
- Platelet count <100x109/L
- Haemoglobin <90 g/L
- Alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
- Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
- Total bilirubin (TBL) >1.5 times ULN, TBL >3 times ULN in patients with documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or in the presence of liver metastases
- Creatinine >1.5 times ULN concurrent with creatinine clearance <50 mL/min (measured or calculated by Cockcroft and Gault equation), confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD6094 or gefitinib
- History of hypersensitivity to active or inactive excipients of AZD6094 or gefitinib or drugs with a similar chemical structure or class to AZD6094 or gefitinib. Unable to undergo an MRI or contrast CT procedures
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. Insufficient lung function dependent on supplemental oxygen (determined by either clinical examination or an arterial oxygen tension (PaO2) of <70 Torr)
- Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
- Involvement in the planning and conduct of the study (applies to AstraZeneca staff or staff at the study site)
Previous enrolment in the present study
In addition, the following are considered criteria for exclusion from the exploratory genetic research:
- Previous allogeneic bone marrow transplant
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: Volitinib (AZD6094) 600mg + gefitinib 250 mg
Cohort 1: Volitinib(AZD6094) 600 mg od + gefitinib 250 mg od
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600mg or 800mg QD: Patients may continue to receive the treatment as long as they are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Altri nomi:
250mg QD: Patients may continue to receive the treatment as long as they are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Altri nomi:
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Sperimentale: Volitinib (AZD6094) 800mg + gefitinib 250 mg
Cohort 2: Volitinib(AZD6094) 800 mg od + gefitinib 250 mg od
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250mg QD: Patients may continue to receive the treatment as long as they are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Number of adverse events and serious adverse events
Lasso di tempo: From ICF signed to within 28 days after the last dose
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the grade of AE event according to CTC AE 4.0
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From ICF signed to within 28 days after the last dose
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
The Pharmacokinetics (PK) profiles of AZD6094
Lasso di tempo: Cycle 1 Day1 and Day 15
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Peak Plasma Concentration (Cmax)
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Cycle 1 Day1 and Day 15
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The Pharmacokinetics (PK) profiles of AZD6094
Lasso di tempo: Cycle 1 Day1 and Day 15
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Area under the plasma concentration versus time curve (AUC)
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Cycle 1 Day1 and Day 15
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Progression-free survival (PFS)
Lasso di tempo: from enrolled until progression or death due to any cause, assessed up to 2 year
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6-months PFS, 12 months PFS and 24 month PFS
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from enrolled until progression or death due to any cause, assessed up to 2 year
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Disease control rate(DCR)
Lasso di tempo: 12 weeks and 24 weeks
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CR+PR+SD
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12 weeks and 24 weeks
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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Yilong Wu, Prof., Guangdong Provincial People's Hospital
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie delle vie respiratorie
- Neoplasie
- Malattie polmonari
- Neoplasie per sede
- Neoplasie delle vie respiratorie
- Neoplasie toraciche
- Carcinoma, broncogeno
- Neoplasie bronchiali
- Neoplasie polmonari
- Carcinoma, polmone non a piccole cellule
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Agenti antineoplastici
- Inibitori della chinasi proteica
- Gefitinib
Altri numeri di identificazione dello studio
- D5080C00001
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Carcinoma polmonare non a piccole cellule
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