Solid TumorsPhase 1NCT02058901
Study of High-dose, Intermittent Sunitinib in Patients With Solid Tumors.
A Phase 1 study testing Sunitinib in people with Solid Tumors, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The primary objective of this study is: To determine the maximum tolerated dose (MTD) of sunitinib when administered once weekly or once every two weeks. To assess the safety and tolerability of sunitinib in a once weekly or once every two weeks dose schedule. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Sunitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 1 siteNetherlands
- Study dates
- Jul 2013to Jun 2019
- 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
- Signed (by the patient or legally acceptable representative) and dated Informed Consent Form
- Histological or cytological documentation of incurable locally advanced or metastatic solid malignancy for which no standard therapy exists.
- Primary tumor or metastatic site must be accessible for biopsy. Patients eligible for the expansion cohort must be willing to undergo tumor biopsies, while tumor biopsy remains optional for patients enrolled in the escalation cohort. 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 dose escalation cohorts; at least 1 target lesion for dose expansion cohort).
- Patients must have documented radiographic or clinical progressive disease.
- Age ≥ 18 years.
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- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Normal 12-lead ECG (clinically insignificant abnormalities permitted), and Left Ventricular Ejection Fraction (LVEF) > 50% by multigated acquisition (MUGA) scan or echocardiogram.
- Normal regulated thyroid function- suppletion or blocking drugs permitted.
- Urinalysis: no clinically significant abnormalities.
- 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)
- ALT and AST 2.5 x ULN (In case of liver metastases: < 5 x ULN)
- Alkaline phosphatase < 4 x 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)
- Patients with known Gilbert's disease who have serum bilirubin <= 3x ULN may be enrolled.
- Pregnant or breast-feeding subjects: Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. For fertile men or women of childbearing potential: documented willingness to use a highly effective means of contraception (e.g., hormonal methods [implants, injectables, or combined oral contraceptives], intrauterine devices, sexual abstinence, or vasectomized or surgically sterilized partner). Contraception is necessary for at least 6 months after receiving the study kinase inhibitor.
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.
- 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.
- jor 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.)
- Known hypersensitivity to sunitinib or to its excipients.
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- Presence of any significant central nervous system or psychiatric disorder(s) that would interfere with the patient's compliance.
- Drug or alcohol abuse.
- Females who are pregnant or breast-feeding.
- 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.
- No chemotherapy, radiotherapy, or biologic therapy within the previous 4 weeks; no nitrosoureas or mitomycin C within the previous 6 weeks; no 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 improvement 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.
- Note: Prior sunitinib therapy does not constitute an exclusion criterion.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of High-dose, Intermittent Sunitinib in Patients With Solid Tumors.
The primary objective of this study is:
- To determine the maximum tolerated dose (MTD) of sunitinib when administered once weekly or once every two weeks.
- To assess the safety and tolerability of sunitinib in a once weekly or once every two weeks dose schedule.
Read the detailed description
Our hypothesis is that sunitinib, when given in a high-dose, intermittent schedule may exhibit improved efficacy with an acceptable toxicity profile. In the present phase I trial, we aim to determine the maximum tolerated dose of sunitinib when administered high-dose, once weekly or once every two weeks. Furthermore, by acquiring skin and tumor biopsies, we will assess intratumoral concentrations of sunitinib, correlate these to skin and plasma concentrations and gain more insight into the biological effects of the drug. Additionally, we aim to preliminary assess the efficacy of sunitinib administered at the MTD level in both schedules. Known serum angiogenesis markers will be correlated to efficacy endpoints.
- Conditions
- Solid Tumors
- Being tested
- Sunitinib
- Keywords
- sunitinib, solid tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib high dose, weekly schedule | Experimental | Initial dose of sunitinib is set at 200 mg once weekly. Three patients are treated at the current dose level. If at least 2 patients are observed to have Dose Limiting Toxicity (DLT), the prior dose level is defined as the Maximum Tolerated Dose (MTD) (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 patients are observed to have DLT, the dose level is escalated one step for the next cohort of 3 patients. If exactly 1 of the 3 patients treated show DLT, 3 additional patients are treated at the current dose level. If none of these show DLT, the dose level is escalated for the next cohort of 3 patients; otherwise, the prior dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). A tentative MTD becomes final when a total of 6 patients are treated with less than 2 showing DLT Receives: Drug: Sunitinib |
| Sunitinib high dose, biweekly schedule | Experimental | When the final MTD is reached for the cohort of patients treated once weekly and depending on the toxicities developed and defining MTD, enrollment of patients in the once every 2 weeks escalation cohort will begin, with the initial dose set at the MTD dose of the once weekly schedule, escalating again at 100 mg increments per dose level. Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum tolerated dose (MTD) of sunitinib
Measured: 6 weeks
Number of participants with serious and non-serious adverse events
Measured: 6 weeks
Secondary outcomes (4)
Calculation of maximum plasma drug concentration, sunitinib half life, Area Under the Concentration-Time Curve (AUC 0-48h), clearance and volume of distribution
Measured: Prior to the initial dose on day 1 and 2, 4, 6, 8, 10, 24, and 48 hours post-dose
Time to Disease Progression
Measured: end of study
Recommended phase II dose (RP2D) and the optimal dose schedule
Measured: End of study
Measurement of intratumoral and skin concentration of sunitinib
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2014 (estimated)
- Study startJul 2013
- Primary completionJun 2019
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies 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
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 101 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
- NCT02058901
- Sponsor's protocol ID
- 2013/75
- Other IDs
- 2012-005756-41
- Status last verified
- Jul 2019
- First submitted
- 30 Sep 2013
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rovithi M, Gerritse SL, Honeywell RJ, Ten Tije AJ, Ruijter R, Peters GJ, Voortman J, Labots M, Verheul HMW. Phase I Dose-Escalation Study of Once Weekly or Once Every Two Weeks Administration of High-Dose Sunitinib in Patients With Refractory Solid Tumors. J Clin Oncol. 2019 Feb 10;37(5):411-418. doi: 10.1200/JCO.18.00725. Epub 2018 Dec 26.
PubMed 30586316
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of High-dose, Intermittent Sunitinib in Patients With Solid Tumors.
- ClinicalTrials.gov ID
- NCT02058901
- Acronym / sponsor ID
- 2013/75
- Conditions
- Solid Tumors
- Keywords
- sunitinib, solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 10 Feb 2014 (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.
The primary objective of this study is:
- To determine the maximum tolerated dose (MTD) of sunitinib when administered once weekly or once every two weeks.
- To assess the safety and tolerability of sunitinib in a once weekly or once every two weeks dose schedule.
Detailed description
Our hypothesis is that sunitinib, when given in a high-dose, intermittent schedule may exhibit improved efficacy with an acceptable toxicity profile. In the present phase I trial, we aim to determine the maximum tolerated dose of sunitinib when administered high-dose, once weekly or once every two weeks. Furthermore, by acquiring skin and tumor biopsies, we will assess intratumoral concentrations of sunitinib, correlate these to skin and plasma concentrations and gain more insight into the biological effects of the drug. Additionally, we aim to preliminary assess the efficacy of sunitinib administered at the MTD level in both schedules. Known serum angiogenesis markers will be correlated to efficacy endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sunitinib high dose, weekly schedule | Experimental | Drug: SunitinibInitial dose of sunitinib is set at 200 mg once weekly. Three patients are treated at the current dose level. If at least 2 patients are observed to have Dose Limiting Toxicity (DLT), the prior dose level is defined as the Maximum Tolerated Dose (MTD) (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 patients are observed to have DLT, the dose level is escalated one step for the next cohort of 3 patients. If exactly 1 of the 3 patients treated show DLT, 3 additional patients are treated at the current dose level. If none of these show DLT, the dose level is escalated for the next cohort of 3 patients; otherwise, the prior dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). A tentative MTD becomes final when a total of 6 patients are treated with less than 2 showing DLT |
| Sunitinib high dose, biweekly schedule | Experimental | Drug: SunitinibWhen the final MTD is reached for the cohort of patients treated once weekly and depending on the toxicities developed and defining MTD, enrollment of patients in the once every 2 weeks escalation cohort will begin, with the initial dose set at the MTD dose of the once weekly schedule, escalating again at 100 mg increments per dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Signed (by the patient or legally acceptable representative) and dated Informed Consent Form
- Histological or cytological documentation of incurable locally advanced or metastatic solid malignancy for which no standard therapy exists.
- Primary tumor or metastatic site must be accessible for biopsy. Patients eligible for the expansion cohort must be willing to undergo tumor biopsies, while tumor biopsy remains optional for patients enrolled in the escalation cohort. 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 dose escalation cohorts; at least 1 target lesion for dose expansion cohort).
- Patients must have documented radiographic or clinical progressive disease.
Key exclusion criteria (20 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.
- 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.
- jor 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.)
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 |
|---|---|---|
| Sunitinib | Drug | Sunitinib high dose, biweekly schedule, Sunitinib high dose, weekly schedule |
Primary outcome
maximum tolerated dose (MTD) of sunitinib
Time frame: 6 weeks
Number of participants with serious and non-serious adverse events
Time frame: 6 weeks
4 secondary outcomes
Calculation of maximum plasma drug concentration, sunitinib half life, Area Under the Concentration-Time Curve (AUC 0-48h), clearance and volume of distribution
Time frame: Prior to the initial dose on day 1 and 2, 4, 6, 8, 10, 24, and 48 hours post-dose
Time to Disease Progression
Time frame: end of study
Recommended phase II dose (RP2D) and the optimal dose schedule
Time frame: End of study
Measurement of intratumoral and skin concentration of sunitinib
Time frame: 2 weeks
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 17 Jul 2019.
- Derived from this study: PubMed 30586316Rovithi M, Gerritse SL, Honeywell RJ, Ten Tije AJ, Ruijter R, Peters GJ, Voortman J, Labots M, Verheul HMW. Phase I Dose-Escalation Study of Once Weekly or Once Every Two Weeks Administration of High-Dose Sunitinib in Patients With Refractory Solid Tumors. J Clin Oncol. 2019 Feb 10;37(5):411-418. doi: 10.1200/JCO.18.00725. Epub 2018 Dec 26.
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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.
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 Sunitinib in people with Solid Tumors, 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 22 inclusion and 20 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 17 Jul 2019. 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?
maximum tolerated dose (MTD) of sunitinib (time frame: 6 weeks). The study lists 2 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 NCT02058901, which also lists 1 linked publication.
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 Jul 2019.