Comparative Study of Individualized Sensitivity-Directed Chemotherapy Versus DTIC
NCT ID: NCT00779714
Last Updated: 2008-10-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE3
360 participants
INTERVENTIONAL
2008-10-31
2013-04-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Two question are aimed to be answered by this study:
1. Is the individual chemosensitivity index (BICSI) a prognostic / predictive biomarker for chemotherapy ?
2. Is an individualized, sensitivity-directed combination chemotherapy superior to the standard regimen DTIC in terms of survival and response ?
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Therefore, chemotherapy still is considered as the main therapeutic option in advanced metastatic melanoma, and a number of non-standard chemotherapeutics have been tested in small pilot studies to improve treatment efficacy. Even though complete remissions of metastatic lesions could only be observed in a few patients, these observations indicate a subgroup of patients exhibiting high sensitivity to certain anticancer drugs. An in vitro ATP-based chemosensitivity assay has been shown to differentiate between chemosensitive and chemoresistant melanoma patients. A phase-II-study testing this assay in 53 metastatic melanoma patients followed by a sensitivity-directed individualized chemotherapy demonstrated, that the chemosensitivity profile of an individual patient, reflected by the best individual chemosensitivity index (BICSI), correlated with therapy outcome in terms of therapy response and patient overall survival (Ugurel S: Clin Cancer Res 2006). Interestingly, a surprisingly high proportion of about 2/5 of the investigated patient cohort were classified as chemosensitive, the remaining 3/5 were classified as chemoresistant. Objective response was 36.4% in chemosensitive patients compared to 16.1% in chemoresistant patients (p=0.114); progression arrest (CR+PR+SD) was 59.1% versus 22.6% (p=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared to 7.4 months in chemoresistant patients (p=0.041).
These encouraging results prompted the initiation of this randomized phase-III-trial investigating an individualized sensitivity-directed combination chemotherapy compared to the current standard treatment DTIC, as first-line treatment in metastatic melanoma. The therapeutics for chemosensitivity testing and treatment of patients were chosen considering the results of the phase-II-trial (paclitaxel+cisplatinum, treosulfan+cytarabine).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
A (individualized combined chemotherapy)
paclitaxel + cisplatin
paclitaxel 200 mg/m2 cisplatin 50 mg/m2 d1 every 21 days
treosulfan + cytarabine
treosulfan 2500 mg/m2, d2 cytarabine 100 mg/m2, d1-3 every 21 days
B (DTIC monochemotherapy)
DTIC (dacarbazine)
1000 mg/m2, d1 every 21 days
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
DTIC (dacarbazine)
1000 mg/m2, d1 every 21 days
paclitaxel + cisplatin
paclitaxel 200 mg/m2 cisplatin 50 mg/m2 d1 every 21 days
treosulfan + cytarabine
treosulfan 2500 mg/m2, d2 cytarabine 100 mg/m2, d1-3 every 21 days
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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)
* total and direct serum bilirubin ≤ 2 times UNL
* GOT or GPT ≤ 2.5 times UNL; ≤ 5 times UNL is allowed in case of liver metastasis
* alkaline phosphatase \< 2.5 times UNL
* Female patients should not be pregnant or nursing. Women of childbearing potential should be using a highly effective method of birth control (e.g. implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner). For subjects using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on the contraceptive should be addressed.
* Male patients should use an effective method of contraception.
* Before registration, written informed consent must be given according to GCP guidelines and national/local regulations. Patients must be willing and giving informed consent to participation in the trial.
* 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.
Exclusion Criteria
* 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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Hiege-Stiftung gegen Hautkrebs
UNKNOWN
medac GmbH
INDUSTRY
DCS Innovative Diagnostik Systeme
UNKNOWN
University of Wuerzburg
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Dept of Dermatology, University of Wuerzburg
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Selma Ugurel, Prof. (MD)
Role: STUDY_CHAIR
Dept of Dermatology, University of Wuerzburg
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Dept of Dermatology, University of Aachen
Aachen, , Germany
Dept of Dermatology, University of Berlin Charite
Berlin, , Germany
Dept of Dermatology, University of Bochum
Bochum, , Germany
Medizinisches Zentrum Bonn Friedensplatz
Bonn, , Germany
Dept of Dermatology, University of Essen
Essen, , Germany
Dermatology, Klinikum Frankfurt/Oder
Frankfurt (Oder), , Germany
Dept of Dermatology, University of Frankfurt
Frankfurt am Main, , Germany
Dept of Dermatology, University of Hannover
Hanover, , Germany
Dept of Dermatology, Saarland University
Homburg/Saar, , Germany
Dept of Dermatology, University of Jena
Jena, , Germany
Dept of Dermatology, University of Schleswig-Holstein Campus Kiel
Kiel, , Germany
Dermatology, Klinikum Ludwishafen
Ludwigshafen, , Germany
Dept of Dermatology, University of Schleswig-Holstein Campus Luebeck
Lübeck, , Germany
Dept of Dermatology, Univeristy of Magdeburg
Magdeburg, , Germany
Dept of Dermatology, University of Mainz
Mainz, , Germany
Dept of Dermatology, University of Mannheim
Mannheim, , Germany
Dept of Dermatology, University of Marburg
Marburg, , Germany
Dept of Dermatology, University of Muenchen
München, , Germany
Dept of Dermatology, University of Muenster
Münster, , Germany
Dept of Medical Oncology, Fachklinik Hornheide
Münster, , Germany
Dermatology, Klinikum Dorothea Christiane Erxleben
Quedlinburg, , Germany
Dept of Dermatology, University of Tuebingen
Tübingen, , Germany
Dept of Dermatology, University of Wuerzburg
Würzburg, , Germany
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
Related Links
Access external resources that provide additional context or updates about the study.
Homepage of organization (ADO, DeCOG) conducting this trial
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
EudraCT Nr. 2008-001686-28
Identifier Type: -
Identifier Source: secondary_id
101.321-13/07
Identifier Type: -
Identifier Source: org_study_id