Study of High-dose, Intermittent Sunitinib in Patients With Solid Tumors.

NCT02058901 | Completed Phase 1 DMC

• 2 other identifiers: 2013/752012-005756-41
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Solid Tumors

Keywords

sunitinib; solid tumors

Outcome Measures

Primary Outcomes (2)

• maximum tolerated dose (MTD) of sunitinib

  6 weeks

• Number of participants with serious and non-serious adverse events

  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

  Prior to the initial dose on day 1 and 2, 4, 6, 8, 10, 24, and 48 hours post-dose

• Time to Disease Progression

  end of study

• Recommended phase II dose (RP2D) and the optimal dose schedule

  End of study

• Measurement of intratumoral and skin concentration of sunitinib

  2 weeks

Study Arms (2)

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

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.

Drug: Sunitinib

Interventions

Sunitinib DRUG

Sunitinib high dose, biweekly schedule; Sunitinib high dose, weekly schedule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1081HV, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 30586316 DERIVED

MeSH Terms

Interventions

Sunitinib

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Henk MW Verheul, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: September 30, 2013
• First Posted: February 10, 2014
• Study Start: July 1, 2013
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: July 17, 2019

Record last verified: 2019-07

Locations

NL (1)