SORAVE - Sorafenib and Everolimus in Solid Tumors (SORAVE)

May 24, 2016 updated by: Prof. Dr. Juergen Wolf, University of Cologne

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

Dose finding part: A phase I clinical trial to evaluate the safety of combined sorafenib and everolimus treatment in patients with relapsed solid tumors (finished).

Extension part:Treatment of non-small cell lung cancer (NSCLC) with KRAS mutation after ≥ 1st relapse (recruiting)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Dose finding part: 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.

Extension part: Patients will be treated with a dose of 7,5 mg Everolimus for 14 days (run-in phase) and sorafenib 2x 400 mg until progression

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Cologne, Germany
        • Center for Integrated Oncology, Dep.I of Internal Medicine, University Hospital Cologne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with solid tumors relapsed after and/or refractory to standard therapy (dose finding part), KRAS mutated NSCLC patients after ≥ 1st relapse for the extension phase
  • ≥ 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; for Extension phase: Long QT-Syndrome
  • 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

For Extension part:

  • Patients with medication that prolongs QTc and cannot be withdrawn (if the QTc prolonging medication is withdrawn - there must be a time interval of at least 7 days before starting treatment with sorafenib, in case of amiodarone the time interval is at least 90 days)
  • Testing for Hepatitis B is mandatory

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Therapy with everolimus and sorafenib
Dose finding: Treatment with defined dose of sorafenib of 2x400 mg with increasing dose of everolimus (2.5 mg, 5 mg, 7.5 mg, 10 mg) Extension: Treatment with defined dose of sorafenib of 2x400 mg with everolimus 7.5 mg
Drug: Combination of sorafenib and everolimus
Dose finding: Treatment with defined dose of sorafenib of 2x400 mg with increasing dose of everolimus (2.5 mg, 5 mg, 7.5 mg, 10 mg) Extension: Treatment with defined dose of sorafenib of 2x400 mg with everolimus 7.5 mg
Other Names:
  • Nexavar, RAD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To define a feasible treatment schedule for the combination therapy with sorafenib and everolimus
Time Frame: July 2009 - December 2011
July 2009 - December 2011

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine the maximum tolerated dose (MTDs) of everolimus in combination with 2 x 400 mg sorafenib daily
Time Frame: July 2009 - December 2011
July 2009 - December 2011
To analyze pharmacokinetic (PK) profiles (AUC, Cmax) of sorafenib and everolimus during combination therapy
Time Frame: July 2009 - December 2012
July 2009 - December 2012
To determine the safety profile of the combination therapy with sorafenib + everolimus
Time Frame: July 2009 - December 2012
July 2009 - December 2012
To correlate KRAS-mutation status with treatment response (extension phase)
Time Frame: December 2011 - December 2012
December 2011 - December 2012

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

July 2, 2009

First Submitted That Met QC Criteria

July 6, 2009

First Posted (Estimate)

July 7, 2009

Study Record Updates

Last Update Posted (Estimate)

May 25, 2016

Last Update Submitted That Met QC Criteria

May 24, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SORAVE

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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