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Monocentric Pilot Study Investigating the Metabolic Activity of Melanoma in Vivo During Sorafenib and Dacarbazine

Primary Purpose

Melanoma Stage III or IV, No Prior Chemotherapy

Status

Completed

Phase

Phase 2

Locations

Switzerland

Study Type

Interventional

Intervention

Sorafenib (Nexavar), Dacarbazine (DTIC)

About this trial

This is an interventional treatment trial for Melanoma Stage III or IV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

Age > 18 years.
Histologically or cytologically confirmed unresectable (stage III) or metastatic (stage IV) melanoma for whom treatment with dacarbazine is considered medically acceptable.
No prior chemotherapy.
ECOG Performance Status of 0 or 1.
Life expectancy of at least 12 weeks.
Subjects with at least one uni-dimensional (for RECIST) or bi-dimensional (for WHO) measurable lesion. Lesions must be measured by CT-scan or MRI.
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/ìl. Total bilirubin <= 1.5 times the upper limit of normal. ALT and AST <= 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer). Alkaline phosphatase < 4 x ULN. PT-INR/PTT < 1.5 x upper limit of normal [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.
Signed and dated informed consent before the start of specific protocol procedures.
Baseline serum LDH level > 1.1 ULN.
Assessable metastases (Skin or superficial lymph nodes, minimal diameter 1 cm)

EXCLUSION CRITERIA:

History of cardiac disease: congestive heart failure > NYHA class
active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
History of HIV infection or chronic hepatitis B or C.
Active clinically serious infections (> grade 2 NCI-CTC version 3.0).
Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry).
Patients with seizure disorder requiring medication (such as steroids or anti-epileptics).
History of organ allograft.
Patients with evidence or history of bleeding diathesis.
Patients undergoing renal dialysis.
Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study 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.
Primary ocular melanoma

Sites / Locations

Department of Dermatology, University Hospital Zurich

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Sorafenib and Dacarbacine

Arm Description

Outcomes

Primary Outcome Measures

1) Metabolic activity (glucose-uptake) in vivo, standardised uptake value (SUV) in FDG-PET/CT. 2) Quantification of soluble S100 serum and LDH. 3) Gene expression profile of cutaneous melanoma metastasis

Secondary Outcome Measures

Full Information

NCT ID

NCT00794235

First Posted

November 19, 2008

Last Updated

January 7, 2010

Sponsor

University of Zurich

1. Study Identification

Unique Protocol Identification Number

NCT00794235

Brief Title

Monocentric Pilot Study Investigating the Metabolic Activity of Melanoma in Vivo During Sorafenib and Dacarbazine

Official Title

Monocentric Pilot Study Investigating the Metabolic Activity of Melanoma in Vivo During Sorafenib and Dacarbazine

Study Type

Interventional

2. Study Status

Record Verification Date

January 2010

Overall Recruitment Status

Completed

Study Start Date

December 2008 (undefined)

Primary Completion Date

November 2009 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

University of Zurich

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Investigation of the metabolic activity of sorafenib and sorafenib plus dacarbazine on melanoma metastasis in patients with melanoma stage III or IV on the basis of PET/CT, LDH and S-100 evaluation. As we hypothezise a direct influence on the transcriptome by these drugs via antiproliferative or apoptotic signals, biopsies of melanoma skin metastases will be assessed with microarrays and direct changes will be revealed. If positive effects on the transcriptional profiles of metastases are revealed, patients with metastatic melanomas would benefit from these drugs resulting in tumor regressions. Therefore, a total of 12 patients with skin- or superficial lymph node metastases with a diameter of at least 1 cm will be chosen for sorafenib therapy over 56 days per os twice daily with each 400 mg and, additionally, on day 14 and 42, intravenous dacarbazine infusion (volume depending on the body surface area (1000 mg/m2)). Before treatment with sorafenib, before treatment with dacarbazine, and after treatment, S100 and LDH will be measured in serum, PET/CT will be conducted and biopsy will be taken out of one skin metastasis on the same day.

Detailed Description

A total of 12 patients with skin- or superficial lymph node metastases with a diameter of at least 1 cm will be chosen for sorafenib therapy over 56 days per os twice daily with each 400 mg and, additionally, on day 14 and 42, intravenous dacarbazine infusion (volume depending on the body surface area (1000 mg/m2)). On screening day, the medical history as well as the physical examination with determining the vital signs and the analyzing the coagulation status in the venous blood are conducted. In women, a pregnancy test will be conducted. On screening day, as well as on day 10, 16, 35 and 60, venous blood is taken for examination of hematology (hemoglobin, hematocrit, red blood cell (RBC) count, platelets, white blood cell (WBC) count with differential (total neutrophils, lymphocytes, monocytes, eosinophils and basophils), biochemistry (sodium, potassium, urea, creatinine, phosphate, glucose, alanine aminotransferase (ALT), gGT, alkaline phosphatase, total bilirubin, albumin, total lipid status with LDL-cholesterol, HDL-cholesterol, triglyceride), S-100, LDH, and for asservation of 40 ml EDTA and 10 ml Serum. At every consultation (screening day, day 1, 10, 14, 16, 35, 42, 60), concomitant medication will be recorded, and vital signs will be determined. At every consultation except of screening day and day 1, adverse events will be reported. FDG-PET/CT is conducted on screening day, day 10, 16 and 60; afterward, one cutaneous metastasis which was included in previous PET/CT scan, is biopsied for investigating its gene processing profile (day 60 is optional).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma Stage III or IV, No Prior Chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib and Dacarbacine

Arm Type

Other

Intervention Type

Drug

Intervention Name(s)

Sorafenib (Nexavar), Dacarbazine (DTIC)

Other Intervention Name(s)

Nexavar (Sorafenib).ATC-Code: L01XE05, Dacin (Dacarbazin).ATC-Code: L01AX04

Intervention Description

Sorafenib: 2x400 mg daily PO (2 tablets (200 mg each) each AM and PM). DAY 1-56. DTIC: 1-hour IV infusion 1000mg/m2 DAY 14 and 42.

Primary Outcome Measure Information:

Title

Time Frame

SCREEN: S100, LDH, FDG-PET/CT, biopsy. DAY10: S100, LDH, FDG-PET/CT, biopsy. DAY16: S100, LDH, FDG-PET/CT, biopsy. DAY35: S100, LDH. DAY60: S100, LDH, FDG-PET/CT, biopsy (biopsy is optional). Sorafenib: DAY1-56. DTIC: DAY 14 and 42.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: Age > 18 years. Histologically or cytologically confirmed unresectable (stage III) or metastatic (stage IV) melanoma for whom treatment with dacarbazine is considered medically acceptable. No prior chemotherapy. ECOG Performance Status of 0 or 1. Life expectancy of at least 12 weeks. Subjects with at least one uni-dimensional (for RECIST) or bi-dimensional (for WHO) measurable lesion. Lesions must be measured by CT-scan or MRI. 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/ìl. Total bilirubin <= 1.5 times the upper limit of normal. ALT and AST <= 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer). Alkaline phosphatase < 4 x ULN. PT-INR/PTT < 1.5 x upper limit of normal [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. Signed and dated informed consent before the start of specific protocol procedures. Baseline serum LDH level > 1.1 ULN. Assessable metastases (Skin or superficial lymph nodes, minimal diameter 1 cm) EXCLUSION CRITERIA: History of cardiac disease: congestive heart failure > NYHA class active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. History of HIV infection or chronic hepatitis B or C. Active clinically serious infections (> grade 2 NCI-CTC version 3.0). Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry). Patients with seizure disorder requiring medication (such as steroids or anti-epileptics). History of organ allograft. Patients with evidence or history of bleeding diathesis. Patients undergoing renal dialysis. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study 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. Primary ocular melanoma

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Reinhard Dummer, MD

Organizational Affiliation

Department of Dermatology, University Hospital Zurich, Switzerland

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Dermatology, University Hospital Zurich

City

Zurich

ZIP/Postal Code

8091

Country

Switzerland

12. IPD Sharing Statement

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Monocentric Pilot Study Investigating the Metabolic Activity of Melanoma in Vivo During Sorafenib and Dacarbazine

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