NeoplasmsPhase 1SOPRANONCT02636426
Sorafenib Administered Using a High-dose, Pulsatile Regimen: a Phase I Exposure Escalation Study
A Phase 1 study testing sorafenib in people with Neoplasms, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Sorafenib is an oral anticancer drug and inhibits multiple protein kinases important for tumor growth and metastases, including VEGFR, PDGFR, and RAF kinases. In daily clinical practice it is currently used at a dose of 400 mg twice daily in a continuous schedule. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- sorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2015to 27 Dec 2017
- Phase
- Phase 1
- 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
- Histological or cytological documentation of incurable locally advanced or metastatic solid malignancy for which no standard therapy exists.
- Patients eligible for the expansion cohort must be willing to undergo tumor and skin biopsies, while tumor and skin biopsies are optional for patients enrolled in the escalation cohort. Primary tumor or metastatic site must be accessible for biopsy. Bone metastases are excluded as a biopsy site.
- Evaluable disease by RECIST version 1.1. criteria (see appendix III; at least 1 target or non-target lesion for the dose escalation cohorts; at least 1 target lesion the for dose expansion cohorts).
- Patients must have documented radiographic or clinical progressive disease.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (appendix IV).
Show all 19Show fewer
- Normal 12-lead ECG (clinically insignificant abnormalities permitted), and left ventricular ejection fraction (LVEF) > 50% evaluated by multigated acquisition scan (MUGA) or echocardiogram.
- Normal or regulated thyroid function - supplementation or blocking drugs permitted.
- Urine analysis: no clinically significant abnormalities.
- Albumin higher than 25 g/L.
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to screening:
- Hemoglobin ≥ 5,6 mmol/L
- Absolute neutrophil count (ANC) ≥ 1,5 x 10*9/l
- Platelet count ≥ 100 x 10*9/l
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Patients with known Gilbert's disease who have serum bilirubin ≤ 3x ULN may be enrolled.
- ALT and AST ≤ 2.5 x ULN (in case of liver metastases: ≤ 5 times ULN).
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min (based on MDRD).
- PT-INR/PTT < 1.5 x ULN, unless coumarin derivatives are used.
- Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed, if this treatment can be interrupted for a biopsy as judged by the treating physician).
Who cannot join
- Evidence of a significant uncontrolled concomitant disease, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmia, clinically significant valvular heart disease and unstable angina); nervous system, pulmonary (including obstructive pulmonary disease and history of symptomatic bronchospasm), renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture.
- Prior radiotherapy in the abdominal or thoracic area or in > 3 vertebrae in the spine (if long interval since previous radiotherapy or radiotherapy in ≤ 3 vertebrae, eligibility will be decided on an individual basis by the primary investigator).
- Poorly controlled hypertension despite adequate blood pressure medication. Blood pressure must be ≤ 160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements.
- Seizure disorders requiring anticonvulsant therapy.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to day 1, without complete recovery.
- Known active bacterial, viral, fungal, mycobacterial, or other infection (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds).
Show all 21Show fewer
- Known hypersensitivity to sorafenib or to its excipients.
- Presence of any significant central nervous system or psychiatric disorder(s) that would interfere with the patient's compliance.
- Drug or alcohol abuse.
- Any evidence of a disease or condition that might affect compliance with the protocol or interpretation of the study results or render the patient at high risk from treatment complications.
- Unwillingness or inability to comply with study and follow-up procedures.
- Chemotherapy, radiotherapy, or biologic therapy within the previous 4 weeks; Nitrosoureas or mitomycin C within the previous 6 weeks; Investigational agents within the previous 4 weeks.
- Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
- Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control).
- Patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:
- Presence of evaluable or measurable disease outside the CNS
- Radiographic demonstration of stabilization upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNS-directed therapy and the screening radiographic study
- Completion of radiotherapy ≥ 8 weeks prior to the screening radiographic study
- Discontinuation of corticosteroids and anticonvulsants ≥ 4 weeks prior to the screening radiographic study
- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, or diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving the study protein kinase inhibitor.
- Concomitant medication with drugs having proarrhythmic potential (such as sotalol, haloperidol, flecainide) is not permitted during the study.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1081 HV
About this study
Official title: Sorafenib Administered Using a High-dose, Pulsatile Regimen in Patients With Advanced Solid Malignancies: a Phase I Exposure Escalation Study
Sorafenib is an oral anticancer drug and inhibits multiple protein kinases important for tumor growth and metastases, including VEGFR, PDGFR, and RAF kinases. In daily clinical practice it is currently used at a dose of 400 mg twice daily in a continuous schedule. In this phase I study patients will be treated with a new dosing schedule of sorafenib: i.e. a high-dose, pulsatile schedule. The tolerability and safety of this new schedule is examined in exposure escalation cohorts based on a target plasma AUC0-12h (area under the curve). Exposure escalation cohorts are used instead of conventional dose escalation cohorts because the effect of a drug is dependent of its AUC levels and large differences in plasma sorafenib AUC0-12h have previously been shown between patients treated at the same dose level. Using pharmacokinetic monitoring, the sorafenib dose will be adjusted to a target plasma AUC0-12h. The escalation cohorts consist of 3-6 patients per exposure level starting with a target plasma sorafenib AUC0-12h level of 25-50 mg/L/h. After the determination of the maximum tolerated AUC0-12h, 10 additional patients will be entered into an expansion cohort. In the expansion cohort the patients will be treated with a weekly pulse of sorafenib at the maximum tolerated AUC0-12h for further assessment of safety and preliminary exploration of efficacy.
Read the detailed description
Rationale: Preclinical research showed improved efficacy of sorafenib when given in a high-dose, pulsatile schedule compared with conventional (lower dose) continuous scheduling as a result of higher peak concentrations in the tumor. In this phase I study patients will be treated with high-dose, pulsatile sorafenib in exposure escalation cohorts. Exposure escalations cohorts are based on a target plasma AUC0-12h (area under the curve) and are used instead of conventional dose escalation cohorts because the effect of a drug is dependent of its AUC levels and large differences in plasma sorafenib AUC0-12h have previously been shown between patients treated at the same dose level.
Primary Objectives:
- To determine the maximum tolerated plasma AUC0-12h of high-dose sorafenib administered in a weekly, pulsatile schedule.
- To assess the safety and tolerability of high-dose, pulsatile sorafenib.
Secondary Objectives:
- To determine the pharmacokinetic behaviour of sorafenib and its major active metabolite pyridine N-oxide when administered in a weekly, pulsatile schedule.
- To determine a recommended phase II plasma AUC0-12h of high-dose sorafenib in a weekly pulsatile schedule.
- Preliminary assessment of the efficacy of high-dose, pulsatile sorafenib administered at the maximum tolerated plasma AUC0-12h.
- To determine skin and intratumoral concentrations of sorafenib and their correlation with plasma and whole blood concentrations.
- To select 1-2 optimal time points from the AUC0-12h data to determine sorafenib exposure using a finger puncture.
Study design: A single center, open-label, phase I study of high-dose, pulsatile sorafenib administered in exposure escalation cohorts.
Study population: Adult patients with locally advanced or metastatic disease for whom no standard therapy exists.
Treatment: Patients will be treated in exposure escalation cohorts with high-dose sorafenib administered in a weekly pulsatile schedule. Using pharmacokinetic monitoring, the sorafenib dose will be adjusted to a target plasma AUC0-12h. The escalation cohorts consist of 3-6 patients per exposure level starting with a target plasma sorafenib AUC0-12h level of 25-50 mg/L/h. After the determination of the maximum tolerated AUC0-12h, 10 additional patients will be entered into an expansion cohort. In the expansion cohort the patients will be treated with a weekly pulse of sorafenib at the maximum tolerated AUC0-12h for further assessment of safety and preliminary exploration of efficacy.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenibDrug
Also called Nexavar
In new dosing schedule of sorafenib is investigated in this study: high-dose, pulsatile sorafenib
| Study group | Role | What they receive |
|---|---|---|
| sorafenib | Experimental | In this phase I study patients are treated with high-dose, pulsatile sorafenib in escalating AUC0-12h cohorts. Receives: Drug: sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated plasma AUC0-12h of high-dose, pulsatile sorafenib
Toxicity is graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.
Measured: The exposure limiting toxicity period is within the first 42 days from the start of treatment. The maximum tolerated AUC0-12h of sorafenib is determined after completion of the escalation part of the study. It is expected to be completed within one year.
Secondary outcomes (8)
AUC0-12h of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Measured: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
Cmax of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Measured: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
Tmax of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Measured: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
T1/2 of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Measured: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
Recommended phase II dose
Measured: This depends on the maximum tolerated AUC0-12h of sorafenib. The maximum tolerated AUC0-12h of sorafenib is determined after completion of the escalation part of the study. It is expected to be completed within one year.
Preliminary efficacy i.e. response rate, progression free survival and overall survival.
In an expansion cohort, 10 extra patients will be treated with high-dose, pulsatile sorafenib administrated at the maximum tolerated AUC. Before treatment and every 8 weeks during treatment CT thorax and abdomen will be performed and evaluated according to RECIST version 1.1.
Measured: From start of treatment until the date of death from any cause, assessed up to 100 months
Intratumoral and skin concentrations of sorafenib
Biopsies are only mandatory in the patients included in the expansion cohort. Concentrations are measured in biopsies using LC/MS/MS.
Measured: After 2 weeks of treatment.
Optimal timepoints for finger puncture to determine sorafenib exposure
Finger punctures are only mandatory in de patients included in the expansion cohort. The results of the finger puncture will be compared with plasma and whole blood venous PK samples used for the AUC0-12h. The aim is to simplify full pharmacokinetic AUC sampling and to develop a method that can easily guide dose-adjustments based on sorafenib exposure.
Measured: The finger punctures will be performed during the first three cycles (i.e. at day 1, 8 and 15)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2015 (estimated)
- Study startSep 2015
- Primary completion27 Dec 2017
- Study completion27 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, H.M.W. Verheul, Amsterdam UMC, location VUmc
- Investigators
- Henk MW Verheul, MD PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02636426
- Sponsor's protocol ID
- 2015.224
- Acronym
- SOPRANO
- Status last verified
- Oct 2018
- First submitted
- 2 Dec 2015
- Last updated
- 22 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Strumberg D, Richly H, Hilger RA, Schleucher N, Korfee S, Tewes M, Faghih M, Brendel E, Voliotis D, Haase CG, Schwartz B, Awada A, Voigtmann R, Scheulen ME, Seeber S. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 2005 Feb 10;23(5):965-72. doi: 10.1200/JCO.2005.06.124. Epub 2004 Dec 21.
PubMed 15613696Pecuchet N, Lebbe C, Mir O, Billemont B, Blanchet B, Franck N, Viguier M, Coriat R, Tod M, Avril MF, Goldwasser F. Sorafenib in advanced melanoma: a critical role for pharmacokinetics? Br J Cancer. 2012 Jul 24;107(3):455-61. doi: 10.1038/bjc.2012.287. Epub 2012 Jul 5.
PubMed 22767146Wang X, Zhang L, Goldberg SN, Bhasin M, Brown V, Alsop DC, Signoretti S, Mier JW, Atkins MB, Bhatt RS. High dose intermittent sorafenib shows improved efficacy over conventional continuous dose in renal cell carcinoma. J Transl Med. 2011 Dec 21;9:220. doi: 10.1186/1479-5876-9-220.
PubMed 22188900Honeywell R, Yarzadah K, Giovannetti E, Losekoot N, Smit EF, Walraven M, Lind JS, Tibaldi C, Verheul HM, Peters GJ. Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 May 1;878(15-16):1059-68. doi: 10.1016/j.jchromb.2010.03.010. Epub 2010 Mar 15.
PubMed 20382575
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sorafenib Administered Using a High-dose, Pulsatile Regimen in Patients With Advanced Solid Malignancies: a Phase I Exposure Escalation Study
- ClinicalTrials.gov ID
- NCT02636426
- Acronym / sponsor ID
- SOPRANO / 2015.224
- Conditions
- Neoplasms
- Keywords
- phase I study, sorafenib, high-dose schedule, pharmacokinetics, drug monitoring
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- 27 Dec 2017 (actual)
- Study completion
- 27 Dec 2017 (actual)
- First posted
- 21 Dec 2015 (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.
Sorafenib is an oral anticancer drug and inhibits multiple protein kinases important for tumor growth and metastases, including VEGFR, PDGFR, and RAF kinases. In daily clinical practice it is currently used at a dose of 400 mg twice daily in a continuous schedule. In this phase I study patients will be treated with a new dosing schedule of sorafenib: i.e. a high-dose, pulsatile schedule. The tolerability and safety of this new schedule is examined in exposure escalation cohorts based on a target plasma AUC0-12h (area under the curve). Exposure escalation cohorts are used instead of conventional dose escalation cohorts because the effect of a drug is dependent of its AUC levels and large differences in plasma sorafenib AUC0-12h have previously been shown between patients treated at the same dose level. Using pharmacokinetic monitoring, the sorafenib dose will be adjusted to a target plasma AUC0-12h. The escalation cohorts consist of 3-6 patients per exposure level starting with a target plasma sorafenib AUC0-12h level of 25-50 mg/L/h. After the determination of the maximum tolerated AUC0-12h, 10 additional patients will be entered into an expansion cohort. In the expansion cohort the patients will be treated with a weekly pulse of sorafenib at the maximum tolerated AUC0-12h for further assessment of safety and preliminary exploration of efficacy.
Detailed description
Rationale: Preclinical research showed improved efficacy of sorafenib when given in a high-dose, pulsatile schedule compared with conventional (lower dose) continuous scheduling as a result of higher peak concentrations in the tumor. In this phase I study patients will be treated with high-dose, pulsatile sorafenib in exposure escalation cohorts. Exposure escalations cohorts are based on a target plasma AUC0-12h (area under the curve) and are used instead of conventional dose escalation cohorts because the effect of a drug is dependent of its AUC levels and large differences in plasma sorafenib AUC0-12h have previously been shown between patients treated at the same dose level.
Primary Objectives:
- To determine the maximum tolerated plasma AUC0-12h of high-dose sorafenib administered in a weekly, pulsatile schedule.
- To assess the safety and tolerability of high-dose, pulsatile sorafenib.
Secondary Objectives:
- To determine the pharmacokinetic behaviour of sorafenib and its major active metabolite pyridine N-oxide when administered in a weekly, pulsatile schedule.
- To determine a recommended phase II plasma AUC0-12h of high-dose sorafenib in a weekly pulsatile schedule.
- Preliminary assessment of the efficacy of high-dose, pulsatile sorafenib administered at the maximum tolerated plasma AUC0-12h.
- To determine skin and intratumoral concentrations of sorafenib and their correlation with plasma and whole blood concentrations.
- To select 1-2 optimal time points from the AUC0-12h data to determine sorafenib exposure using a finger puncture.
Study design: A single center, open-label, phase I study of high-dose, pulsatile sorafenib administered in exposure escalation cohorts.
Study population: Adult patients with locally advanced or metastatic disease for whom no standard therapy exists.
Treatment: Patients will be treated in exposure escalation cohorts with high-dose sorafenib administered in a weekly pulsatile schedule. Using pharmacokinetic monitoring, the sorafenib dose will be adjusted to a target plasma AUC0-12h. The escalation cohorts consist of 3-6 patients per exposure level starting with a target plasma sorafenib AUC0-12h level of 25-50 mg/L/h. After the determination of the maximum tolerated AUC0-12h, 10 additional patients will be entered into an expansion cohort. In the expansion cohort the patients will be treated with a weekly pulse of sorafenib at the maximum tolerated AUC0-12h for further assessment of safety and preliminary exploration of efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sorafenib | Experimental | Drug: sorafenibIn this phase I study patients are treated with high-dose, pulsatile sorafenib in escalating AUC0-12h cohorts. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histological or cytological documentation of incurable locally advanced or metastatic solid malignancy for which no standard therapy exists.
- Patients eligible for the expansion cohort must be willing to undergo tumor and skin biopsies, while tumor and skin biopsies are optional for patients enrolled in the escalation cohort. Primary tumor or metastatic site must be accessible for biopsy. Bone metastases are excluded as a biopsy site.
- Evaluable disease by RECIST version 1.1. criteria (see appendix III; at least 1 target or non-target lesion for the dose escalation cohorts; at least 1 target lesion the for dose expansion cohorts).
- Patients must have documented radiographic or clinical progressive disease.
- Age ≥ 18 years.
Key exclusion criteria (21 listed)
- Evidence of a significant uncontrolled concomitant disease, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmia, clinically significant valvular heart disease and unstable angina); nervous system, pulmonary (including obstructive pulmonary disease and history of symptomatic bronchospasm), renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture.
- Prior radiotherapy in the abdominal or thoracic area or in > 3 vertebrae in the spine (if long interval since previous radiotherapy or radiotherapy in ≤ 3 vertebrae, eligibility will be decided on an individual basis by the primary investigator).
- Poorly controlled hypertension despite adequate blood pressure medication. Blood pressure must be ≤ 160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements.
- Seizure disorders requiring anticonvulsant therapy.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to day 1, without complete recovery.
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 |
|---|---|---|
| sorafenibAlso: NexavarIn new dosing schedule of sorafenib is investigated in this study: high-dose, pulsatile sorafenib | Drug | sorafenib |
Primary outcome
To determine the maximum tolerated plasma AUC0-12h of high-dose, pulsatile sorafenib
Time frame: The exposure limiting toxicity period is within the first 42 days from the start of treatment. The maximum tolerated AUC0-12h of sorafenib is determined after completion of the escalation part of the study. It is expected to be completed within one year.
Toxicity is graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.
8 secondary outcomes
AUC0-12h of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Time frame: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
Cmax of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Time frame: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
Tmax of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Time frame: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
T1/2 of sorafenib and its primary active metabolite pyridine-N-oxide (escalation cohorts)
Time frame: Pharmacokinetics analysis is performed during the first three treatment cycles (i.e. day 1, 8 en 15).
Recommended phase II dose
Time frame: This depends on the maximum tolerated AUC0-12h of sorafenib. The maximum tolerated AUC0-12h of sorafenib is determined after completion of the escalation part of the study. It is expected to be completed within one year.
Preliminary efficacy i.e. response rate, progression free survival and overall survival.
Time frame: From start of treatment until the date of death from any cause, assessed up to 100 months
Intratumoral and skin concentrations of sorafenib
Time frame: After 2 weeks of treatment.
Optimal timepoints for finger puncture to determine sorafenib exposure
Time frame: The finger punctures will be performed during the first three cycles (i.e. at day 1, 8 and 15)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2018.
- Background: PubMed 15613696Strumberg D, Richly H, Hilger RA, Schleucher N, Korfee S, Tewes M, Faghih M, Brendel E, Voliotis D, Haase CG, Schwartz B, Awada A, Voigtmann R, Scheulen ME, Seeber S. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 2005 Feb 10;23(5):965-72. doi: 10.1200/JCO.2005.06.124. Epub 2004 Dec 21.
- Background: PubMed 22767146Pecuchet N, Lebbe C, Mir O, Billemont B, Blanchet B, Franck N, Viguier M, Coriat R, Tod M, Avril MF, Goldwasser F. Sorafenib in advanced melanoma: a critical role for pharmacokinetics? Br J Cancer. 2012 Jul 24;107(3):455-61. doi: 10.1038/bjc.2012.287. Epub 2012 Jul 5.
- Background: PubMed 22188900Wang X, Zhang L, Goldberg SN, Bhasin M, Brown V, Alsop DC, Signoretti S, Mier JW, Atkins MB, Bhatt RS. High dose intermittent sorafenib shows improved efficacy over conventional continuous dose in renal cell carcinoma. J Transl Med. 2011 Dec 21;9:220. doi: 10.1186/1479-5876-9-220.
- Background: PubMed 20382575Honeywell R, Yarzadah K, Giovannetti E, Losekoot N, Smit EF, Walraven M, Lind JS, Tibaldi C, Verheul HM, Peters GJ. Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 May 1;878(15-16):1059-68. doi: 10.1016/j.jchromb.2010.03.010. Epub 2010 Mar 15.
Related trials for Neoplasms
RecruitingPhase 2
A Study to Evaluate the Efficacy of Cemsidomide + Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma
Multiple Myeloma, Relapsed/Refractory Multiple Myeloma
Not yet recruiting
Effect of a Health Belief Model Based Digital Nudge Intervention on Breast Cancer Screening
Breast Cancer Screening, Breast Cancer Awareness
Not yet recruiting
The AYA Oncology Self-care Movement
Acute Lymphobkastic Leukemia, Medication Adherence
Not yet recruitingPhase 1/2
177Lu-DOTA-EB-TATE in Adult Patients With Metastatic, Radioactive Iodine Non-Responsive Oncocytic (Hurthle-Cell) Thyroid Cancer
Thyroid Cancer
RecruitingPhase 2
The COSMYC Trial (COmbined Suppression of MYC)
Metastatic Castration-resistant Prostate Cancer
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.
Henk MW Verheul, MD PhD principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sorafenib in people with Neoplasms, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 21 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: finished, as of the sponsor's last update on 22 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the maximum tolerated plasma AUC0-12h of high-dose, pulsatile sorafenib (time frame: The exposure limiting toxicity period is within the first 42 days from the start of treatment. The maximum tolerated AUC0-12h of sorafenib is determined after completion of the escalation part of the study. It is expected to be completed within one year.). 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 NCT02636426, which also lists 4 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 22 Oct 2018.