Comparative Study of Individualized Sensitivity-Directed Chemotherapy Versus DTIC

NCT00779714 | Unknown Phase 3 DMC

• 2 other identifiers: 101.321-13/07EudraCT Nr. 2008-001686-28
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 23

Brief Summary

This phase III trial is aimed to investigate the efficacy of an individualized, sensitivity-directed combination chemotherapy in comparison to the standard regimen DTIC. Two question are aimed to be answered by this study:

1. 1.Is the individual chemosensitivity index (BICSI) a prognostic / predictive biomarker for chemotherapy ?
2. 2.Is an individualized, sensitivity-directed combination chemotherapy superior to the standard regimen DTIC in terms of survival and response ?

Conditions

Melanoma

Keywords

metastatic (AJCC stage IV); first-line chemotherapy; ex-vivo chemosensitivity profiling; evaluation of biomarkers

Outcome Measures

Primary Outcomes (1)

• Disease-specific overall survival

  4 years

Secondary Outcomes (1)

• Objective response

  4 years

Study Arms (2)

A (individualized combined chemotherapy)

EXPERIMENTAL

Drug: paclitaxel + cisplatin; Drug: treosulfan + cytarabine

B (DTIC monochemotherapy)

ACTIVE COMPARATOR

Drug: DTIC (dacarbazine)

Interventions

DTIC (dacarbazine) DRUG

1000 mg/m2, d1 every 21 days

Also known as: detimedac

B (DTIC monochemotherapy)

paclitaxel + cisplatin DRUG

paclitaxel 200 mg/m2 cisplatin 50 mg/m2 d1 every 21 days

Also known as: taxomedac + cisplatin medac

A (individualized combined chemotherapy)

treosulfan + cytarabine DRUG

treosulfan 2500 mg/m2, d2 cytarabine 100 mg/m2, d1-3 every 21 days

Also known as: ovastat + alexan

A (individualized combined chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed melanoma of the skin, mucosa, or unknown primary, diagnosed with surgically unresectable distant metastases (stage IV according to AJCC).
• At least one measurable target lesion according to RECIST, assessed by CT or MRI (tumor assessment by X-ray or ultrasonography only is not allowed).
• Access to a biopsy of \~1 cm3 from at least one metastatic lesion for in vitro chemosensitivity testing. Cell suspensions from malignant effusions are also eligible.
• No prior chemotherapy in stage IV (adjuvant chemotherapy in stage III allowed; one prior regimen of immunotherapy or targeted therapy in stage IV allowed).
• No evidence of brain/CNS metastases. Former history of brain/CNS metastases, which have been treated successfully, and are no longer visible in CT/MRI is allowed.
• Last complete tumor assessment (CT or MRI of thorax, abdomen and brain) not older than 14 days prior to registration, and not older than 5 weeks prior to onset of study treatment.
• ECOG/WHO performance index of 0 or 1.
• Patients must have stopped any kind of previous antineoplastic therapy for at least 2 weeks prior to registration, and at least 4 weeks prior to treatment onset.
• Patients must not have concurrent or recent malignancies except for surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin. Patients with previous malignancies, which have been treated with a subsequent disease-free interval of at least 5 years, are eligible.
• Patient age ≥ 18 years.
• Adequate hematological, renal and liver function as defined by the following laboratory values performed within 14 days prior to randomisation:
• absolute neutrophil count (ANC) ≥ 1.5 x 109/l
• platelet count ≥ 100 x 109/l
• hemoglobin ≥ 9 g/dl
• urea and serum creatinine ≤ 2 times upper normal limit (UNL)

You may not qualify if:

• All metastatic lesions are surgically resectable.
• Prior chemotherapy in stage IV (adjuvant chemotherapy in stage III allowed; one prior regimen of immunotherapy or targeted therapy in stage IV allowed).
• Primary melanoma of the uvea / choroidea.
• Evidence of brain/CNS metastases. Former history of brain/CNS metastases, which have been treated successfully, and are no longer visible in CT/MRI is allowed.
• ECOG/WHO performance index of 2 or higher
• Concurrent or recent malignancies except for surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin. Patients with previous malignancies, which have been treated with a subsequent disease-free interval of at least 5 years, are eligible.
• Any clinically uncontrolled infectious disease including HIV positivity or AIDS-related illness.
• Any female patients who are pregnant or nursing.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration for the trial.

Sponsors & Collaborators

• University of Wuerzburg: lead
• Hiege-Stiftung gegen Hautkrebs: collaborator
• medac GmbH: collaborator
• DCS Innovative Diagnostik Systeme: collaborator

Study Sites (23)

Dept of Dermatology, University of Aachen

Aachen, 52074, Germany

RECRUITING

Dept of Dermatology, University of Berlin Charite

Berlin, 10117, Germany

RECRUITING

Dept of Dermatology, University of Bochum

Bochum, 44791, Germany

RECRUITING

Medizinisches Zentrum Bonn Friedensplatz

Bonn, 53111, Germany

RECRUITING

Dept of Dermatology, University of Essen

Essen, 45147, Germany

RECRUITING

Dermatology, Klinikum Frankfurt/Oder

Frankfurt (Oder), 15236, Germany

RECRUITING

Dept of Dermatology, University of Frankfurt

Frankfurt am Main, 60590, Germany

RECRUITING

Dept of Dermatology, University of Hannover

Hanover, 30449, Germany

RECRUITING

Dept of Dermatology, Saarland University

Homburg/Saar, 66421, Germany

RECRUITING

Dept of Dermatology, University of Jena

Jena, 07740, Germany

RECRUITING

Dept of Dermatology, University of Schleswig-Holstein Campus Kiel

Kiel, 24105, Germany

RECRUITING

Dermatology, Klinikum Ludwishafen

Ludwigshafen, 67063, Germany

RECRUITING

Dept of Dermatology, University of Schleswig-Holstein Campus Luebeck

Lübeck, 23538, Germany

RECRUITING

Dept of Dermatology, Univeristy of Magdeburg

Magdeburg, 39120, Germany

RECRUITING

Dept of Dermatology, University of Mainz

Mainz, 55131, Germany

RECRUITING

Dept of Dermatology, University of Mannheim

Mannheim, 68167, Germany

RECRUITING

Dept of Dermatology, University of Marburg

Marburg, 35033, Germany

RECRUITING

Dept of Dermatology, University of Muenchen

München, 80337, Germany

RECRUITING

Dept of Dermatology, University of Muenster

Münster, 48149, Germany

RECRUITING

Dept of Medical Oncology, Fachklinik Hornheide

Münster, 48157, Germany

RECRUITING

Dermatology, Klinikum Dorothea Christiane Erxleben

Quedlinburg, 06484, Germany

RECRUITING

Dept of Dermatology, University of Tuebingen

Tübingen, 72086, Germany

RECRUITING

Dept of Dermatology, University of Wuerzburg

Würzburg, 97080, Germany

RECRUITING

Related Publications (4)

• Ugurel S, Schadendorf D, Pfohler C, Neuber K, Thoelke A, Ulrich J, Hauschild A, Spieth K, Kaatz M, Rittgen W, Delorme S, Tilgen W, Reinhold U; Dermatologic Cooperative Oncology Group. In vitro drug sensitivity predicts response and survival after individualized sensitivity-directed chemotherapy in metastatic melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group. Clin Cancer Res. 2006 Sep 15;12(18):5454-63. doi: 10.1158/1078-0432.CCR-05-2763.

  PMID: 17000680 BACKGROUND

• Ugurel S, Tilgen W, Reinhold U. Chemosensitivity testing in malignant melanoma. Recent Results Cancer Res. 2003;161:81-92. doi: 10.1007/978-3-642-19022-3_8.

  PMID: 12528801 BACKGROUND

• Cree IA, Neale MH, Myatt NE, de Takats PG, Hall P, Grant J, Kurbacher CM, Reinhold U, Neuber K, MacKie RM, Chana J, Weaver PC, Khoury GG, Sartori C, Andreotti PE. Heterogeneity of chemosensitivity of metastatic cutaneous melanoma. Anticancer Drugs. 1999 Jun;10(5):437-44. doi: 10.1097/00001813-199906000-00002.

  PMID: 10477162 BACKGROUND

• Andreotti PE, Cree IA, Kurbacher CM, Hartmann DM, Linder D, Harel G, Gleiberman I, Caruso PA, Ricks SH, Untch M, et al. Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma. Cancer Res. 1995 Nov 15;55(22):5276-82.

  PMID: 7585588 BACKGROUND

Related Links

• Homepage of organization (ADO, DeCOG) conducting this trial

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

Dacarbazine; TP protocol; treosulfan; Cytarabine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Selma Ugurel, Prof. (MD)

  Dept of Dermatology, University of Wuerzburg

  STUDY CHAIR

Central Study Contacts

Selma Ugurel, Prof. (MD)

CONTACT

0049931201; Ugurel_S@klinik.uni-wuerzburg.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 22, 2008
• First Posted: October 24, 2008
• Study Start: October 1, 2008
• Primary Completion: October 1, 2012
• Study Completion: April 1, 2013
• Last Updated: October 24, 2008

Record last verified: 2008-10

Locations

DE (23)