Clinical trial NCT00509613: Phase 1 Study With Sorafenib and Sirolimus
Official title: Phase 1 Dose Escalation Study With Sorafenib in Combination With Sirolimus in Patients With Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Refractory to Standard Therapies
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2007-07-31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The purpose of the trial is to identify the recommended dose of sorafenib and sirolimus for combination therapy in subsequent phase 2 trials.


Eligibility criteria: Inclusion Criteria:

* Patients with histological or cytological confirmed advanced solid tumor, which is refractory to standard therapies or for which no standard therapy exists and for which there is a rationale for the therapeutic use of a combination of sorafenib and sirolimus (especially metastic RCC, malignant melanoma, HCC, NSCLC, pancreatic cancer, hormone refractory prostate cancer).
* Men or women of at least 18 years
* Patients who have an ECOG status of 0 or 1
* Patients who have a life expectancy of at least 12 weeks
* Adequate bone marrow, liver and renal function
* Negative pregnancy test for female patients of childbearing potential
* Women and men enrolled into this trial must use adequate birth control measures during the course of the trial.
* Signed informed consent

Exclusion Criteria:

* History of serious cardiac disease
* Active clinically serious bacterial, viral or fungal infections (\> grade 2).
* Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
* Clinically symptomatic brain or meningeal metastasis.
* Patients with seizure disorders requiring medication (such as steroids or antiepileptics).
* Patients with evidence or history of bleeding diathesis.
* Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results.
* Concomitant treatment with strong CYP3A4 inductors (such as rifampicin, St. John´s Wort) or CYP3A4 inhibitors (such as ketoconazole, voriconazole, itraconazole, diltiazem, verapamil, erythromycin). Moderate or weak CYP3A4 modifiers should be used concomitantly only after careful assessment of risk-benefit ratio. Concomitant use of carbamazepine, phenobarbital, phenytoin or chronic use of dexamethasone is excluded

Primary outcomes:
measure: identify the recommended doses for the combination of sorafenib and sirolimus for subsequent phase II studies
Secondary outcomes:
measure: to determine the safety profile of the combination therapy of sorafenib with sirolimus
measure: to determine, if possible, the Maximum Tolerated Dose (MTD) of sorafenib and sirolimus in combination therapy
measure: to analyze pharmacokinetic PK profiles (AUC, Cmax) during combination therapy for sorafenib and sirolimus
measure: to evaluate efficacy of the combination descriptively (response rate and rate of stable diseases)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
Study officials:
affiliation: UMC St Radboud
name: C.M.L. van Herpen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: