SORAVE - Sorafenib and Everolimus in Solid Tumors

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Lung Cancer Group Cologne.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Lung Cancer Group Cologne
ClinicalTrials.gov Identifier:
NCT00933777
First received: July 2, 2009
Last updated: July 1, 2011
Last verified: July 2011
  Purpose

A phase I clinical trial to evaluate the safety of combined sorafenib and everolimus treatment in patients with relapsed solid tumors.


Condition Intervention Phase
Relapsed and/or Refractory Solid Tumors
Drug: Combination of sorafenib and everolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Lung Cancer Group Cologne:

Primary Outcome Measures:
  • To define a feasible treatment schedule for the combination therapy with sorafenib and everolimus [ Time Frame: July 2009 - January 2011 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the maximum tolerated dose (MTDs) of everolimus in combination with 2 x 400 mg sorafenib daily [ Time Frame: July 2009 - January 2011 ] [ Designated as safety issue: Yes ]
  • To analyze pharmacokinetic (PK) profiles (AUC, Cmax) of sorafenib and everolimus during combination therapy [ Time Frame: July 2009 - January 2011 ] [ Designated as safety issue: Yes ]
  • To determine the safety profile of the combination therapy with sorafenib + everolimus [ Time Frame: July 2009 - January 2011 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: July 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therapy with everolimus and sorafenib
Treatment with defined dose of sorafenib of 2x400 mg with increasing dose of everolimus (2.5 mg, 5 mg, 7.5 mg, 10 mg)
Drug: Combination of sorafenib and everolimus
Combination of defined dose of sorafenib (2x400 mg) with increasing dose of everolimus (2.5 mg, 5 mg, 7.5 mg, 10 mg)
Other Name: Nexavar, RAD001

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00933777

Contacts
Contact: Juergen Wolf, MD, Prof. 0049-221-478-89050 lungenkrebs@uk-koeln.de
Contact: Lucia Nogova, MD 0049-221-478-87033 lungenkrebs@uk-koeln.de

Locations
Germany
Center for Integrated Oncology, Dep.I of Internal Medicine, University Hospital Cologne Recruiting
Cologne, Germany
Contact: Juergen Wolf, MD, Prof.    0049-221-478-89050    lungenkrebs@uk-koeln.de   
Sub-Investigator: Lucia Nogova, MD         
Sub-Investigator: Matthias Scheffler, MD         
Sub-Investigator: Karin Toepelt, MD         
Sub-Investigator: Thomas Zander, MD         
Principal Investigator: Juergen Wolf, MD, Prof.         
Sub-Investigator: Andreas Draube, MD         
Sub-Investigator: Sascha Ansen, MD         
Sub-Investigator: Markus Dietlein, MD, Prof.         
Sub-Investigator: Lutz Kracht, MD         
Sponsors and Collaborators
Lung Cancer Group Cologne
Investigators
Principal Investigator: Juergen Wolf, MD, Prof. Lung Cancer Group Cologne, Center for Integrated Oncology, Dep.I of Internal Medicine, University Hospital Cologne, Germany
  More Information

Additional Information:
Publications:

Responsible Party: Prof. Juergen Wolf, MD, Lung Cancer Group Cologne, University Hospital Cologne, Germany
ClinicalTrials.gov Identifier: NCT00933777     History of Changes
Other Study ID Numbers: SORAVE
Study First Received: July 2, 2009
Last Updated: July 1, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Neoplasms
Everolimus
Sirolimus
Sorafenib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014