SORAVE - Sorafenib and Everolimus in Solid Tumors
Information source: Lung Cancer Group Cologne
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Relapsed and/or Refractory Solid Tumors
Intervention: Combination of sorafenib and everolimus (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: Lung Cancer Group Cologne Official(s) and/or principal investigator(s): Juergen Wolf, MD, Prof., Principal Investigator, Affiliation: Lung Cancer Group Cologne, Center for Integrated Oncology, Dep.I of Internal Medicine, University Hospital Cologne, Germany
Overall contact: Juergen Wolf, MD, Prof., Phone: 0049-221-478-89050, Email: lungenkrebs@uk-koeln.de
Summary
A phase I clinical trial to evaluate the safety of combined sorafenib and everolimus
treatment in patients with relapsed solid tumors.
Clinical Details
Official title: SORAVE-Sorafenib and Everolimus in Solid Tumors. A Phase I Clinical Trial to Evaluate the Safety of Combined Sorafenib and Everolimus Treatment in Patients With Relapsed Solid Tumors.
Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To define a feasible treatment schedule for the combination therapy with sorafenib and everolimus
Secondary outcome: To determine the maximum tolerated dose (MTDs) of everolimus in combination with 2 x 400 mg sorafenib dailyTo analyze pharmacokinetic (PK) profiles (AUC, Cmax) of sorafenib and everolimus during combination therapy To determine the safety profile of the combination therapy with sorafenib + everolimus
Detailed description:
Patients will be recruited to receive combination of defined sorafenib dose (2x400mg) with
increasing dose of everolimus (2. 5mg, 5mg, 7. 5mg, 10mg). There will be a run-in phase of 14
days of everolimus followed by combination sorafenib+everolimus starting from day 15. The
combination will be continued as long as it is tolerated by the patient and the patient
benefits from the treatment according to RECIST criteria. The maximal tolerated dose will be
establish in 3+3 design. Patients will be recruited sequentially at least 14 days apart. The
next dose level according to 3+3 design will be initiated if all patients on the previous
dose level reach day 29.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients with solid tumors relapsed after and/or refractory to standard therapy
- ≥ 18 years of age
- Performance status ECOG 0-2
- Life expectancy of at least 12 weeks
- Subjects with at least one measurable (CT or MRI) lesion
- Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin ≥ 9. 0 g/dL
- Absolute neutrophil count (ANC) ≥ 1,500 /mm3
- Platelet count ≥ 100 000/µL
- Total bilirubin ≤ 1,5x upper limit of normal (ULN)
- ALT and AST ≤ 2,5x ULN (≤ 5x ULN for patients with liver involvement)
- Alkaline phosphatase < 4x ULN
- Potassium within normal limits (WNL) or correctable with supplements
- Total calcium (corrected for serum albumin) WNL or correctable with supplements
- Magnesium WNL or correctable with supplements
- PT-INR/PTT < 1. 5 x ULN [Patients who are being therapeutically anticoagulated
with an agent such as coumadin or heparin will be allowed to participate
provided that no prior evidence of underlying abnormality in these parameters
exists]
- Serum creatinine ≤ 1. 5 x upper limit of normal or creatinine clearance (CrCl) ≥
50 ml/min calculated by either Cockcroft-Gault or by 24 hours urine collection
- More than 14 days since previous systemic therapy, radiotherapy and surgery
- Negative urine or serum HCG in women of childbearing potential
- Signed and dated informed consent before the start of specific protocol procedures
Exclusion Criteria:
- Squamous cell carcinoma histology in non-small cell lung cancer
- History of cardiac disease: congestive heart failure > NYHA class 2; active Coronary
Arterial Disease (CAD), (MI more than 6 months prior to study entry is allowed);
cardiac arrythmias requiring anti-arrythmic therapy (except, when controlled by beta
blockers or digoxin) or uncontrolled hypertension
- Active skin, mucosa, ocular or GI disorders of grade > 1
- Uncontrolled diabetes
- ≥ grade 3 hypercholesterolemia/hypertriglyceridemia or ≥ grade 2 hypercholesterolemia
/ hypertriglyceridemia with history of CAD (despite lipid lowering treatment if
given)
- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of everolimus and sorafenib (e. g. ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
bowel resection)
- History of HIV infection or previously sero-positive for the virus
- History of Hepatitis B or/and C or previously sero-positive for the Hepatitis B
or/and C virus
- Leptomeningeal or uncontrolled brain metastases, including patients who continue to
require glucocorticoids or intrathecal chemotherapy for brain or leptomeningeal
metastases (documented by lumbar puncture)
- Treatment with any other investigational drugs within the previous 14 days
- Patients with seizure disorder requiring anti-epileptics
- History of organ allograft
- Patients with evidence or history of bleeding diathesis
- Patients undergoing renal dialysis
- Previous treatment with mTOR inhibitors and/or known hypersensitivity to mTOR
inhibitors
- Past or current history of cancer other than the entry diagnosis EXCEPT cervical
carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis
& T1] or any cancer curatively treated > 3 years prior to study entry
- Any person being in an institution on assignment of the respective authority
- Any medical, mental or psychological condition which in the opinion of the
investigator would not permit the patient to complete the study or understand the
patient information
- Women who are pregnant or breast feeding, or women who are able to conceive and
unwilling to practice an effective method of birth control (safe hormonal methods
or/and barrier contraception) during study and 2 months after the last study drug
intake
Locations and Contacts
Juergen Wolf, MD, Prof., Phone: 0049-221-478-89050, Email: lungenkrebs@uk-koeln.de
Center for Integrated Oncology, Dep.I of Internal Medicine, University Hospital Cologne, Cologne, Germany; Recruiting Juergen Wolf, MD, Prof., Phone: 0049-221-478-89050, Email: lungenkrebs@uk-koeln.de Lucia Nogova, MD, Sub-Investigator Matthias Scheffler, MD, Sub-Investigator Karin Toepelt, MD, Sub-Investigator Thomas Zander, MD, Sub-Investigator Juergen Wolf, MD, Prof., Principal Investigator Andreas Draube, MD, Sub-Investigator Sascha Ansen, MD, Sub-Investigator Markus Dietlein, MD, Prof., Sub-Investigator Lutz Kracht, MD, Sub-Investigator
Additional Information
Related publications: Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, Blumenschein G Jr, Lee JJ, Liu DD, Truong MT, Hong WK, Tran H, Tsao A, Xie D, Ramies DA, Mass R, Seshagiri S, Eberhard DA, Kelley SK, Sandler A. Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol. 2005 Apr 10;23(11):2544-55. Epub 2005 Mar 7. O'Donnell A, Faivre S, Burris HA 3rd, Rea D, Papadimitrakopoulou V, Shand N, Lane HA, Hazell K, Zoellner U, Kovarik JM, Brock C, Jones S, Raymond E, Judson I. Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol. 2008 Apr 1;26(10):1588-95. doi: 10.1200/JCO.2007.14.0988. Epub 2008 Mar 10. Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, Park Y, Liou SH, Marshall B, Boni JP, Dukart G, Sherman ML. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004 Mar 1;22(5):909-18. Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004 Jan 22;350(4):379-92. Review. Erratum in: N Engl J Med. 2009 Apr 30;360(18):1917. Tabernero J, Rojo F, Calvo E, Burris H, Judson I, Hazell K, Martinelli E, Ramon y Cajal S, Jones S, Vidal L, Shand N, Macarulla T, Ramos FJ, Dimitrijevic S, Zoellner U, Tang P, Stumm M, Lane HA, Lebwohl D, Baselga J. Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol. 2008 Apr 1;26(10):1603-10. doi: 10.1200/JCO.2007.14.5482. Epub 2008 Mar 10. Erratum in: J Clin Oncol. 2010 Dec 20;28(36):5350. Stroobants S, Verschakelen J, Vansteenkiste J. Value of FDG-PET in the management of non-small cell lung cancer. Eur J Radiol. 2003 Jan;45(1):49-59. Review. 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. Epub 2004 Dec 21. Moore M, Hirte HW, Siu L, Oza A, Hotte SJ, Petrenciuc O, Cihon F, Lathia C, Schwartz B. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol. 2005 Oct;16(10):1688-94. Epub 2005 Jul 8. Cascone T, Gridelli C, Ciardiello F. Combined targeted therapies in non-small cell lung cancer: a winner strategy? Curr Opin Oncol. 2007 Mar;19(2):98-102. Review.
Starting date: July 2009
Last updated: July 1, 2011
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