Comparative Study of Individualized Sensitivity-Directed Chemotherapy Versus DTIC (ChemoSensMM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by University of Wuerzburg.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Hiege-Stiftung gegen Hautkrebs
medac GmbH
DCS Innovative Diagnostik Systeme
Information provided by:
University of Wuerzburg
ClinicalTrials.gov Identifier:
NCT00779714
First received: October 22, 2008
Last updated: NA
Last verified: October 2008
History: No changes posted
  Purpose

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. 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 ?

Condition Intervention Phase
Melanoma
Drug: DTIC (dacarbazine)
Drug: paclitaxel + cisplatin
Drug: treosulfan + cytarabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospectively Randomized Phase III Study of an Individualized Sensitivity-Directed Combination Chemotherapy Versus DTIC as First-Line Treatment in Stage IV Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by University of Wuerzburg:

Primary Outcome Measures:
  • Disease-specific overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 360
Study Start Date: October 2008
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A (individualized combined chemotherapy) Drug: paclitaxel + cisplatin
paclitaxel 200 mg/m2 cisplatin 50 mg/m2 d1 every 21 days
Other Name: taxomedac + cisplatin medac
Drug: treosulfan + cytarabine
treosulfan 2500 mg/m2, d2 cytarabine 100 mg/m2, d1-3 every 21 days
Other Name: ovastat + alexan
Active Comparator: B (DTIC monochemotherapy) Drug: DTIC (dacarbazine)
1000 mg/m2, d1 every 21 days
Other Name: detimedac

Detailed Description:

Melanoma is a cutaneous neoplasm known for its high aggressiveness, its early dissemination of metastases, and its poor prognosis once metastasized. Chemotherapy with dacarbacine (DTIC) is widely accepted as the standard treatment in metastatic melanoma, with reported response rates of about 10%. This poor outcome is assumed to be due to a high chemoresistance intrinsic to melanoma cells. However, other therapeutic options like polychemotherapy, biochemotherapy, immunotherapy as well as targeted agents did not yet prove to be superior to DTIC in multicenter randomized studies.

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
    • 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.

Exclusion Criteria:

  • 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 severe or uncontrolled hematological, renal or liver dysfunction as defined by the laboratory values given in Inclusion Criteria.
  • 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.
  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: NCT00779714

Contacts
Contact: Selma Ugurel, Prof. (MD) 0049931201 ext 26118 Ugurel_S@klinik.uni-wuerzburg.de

Locations
Germany
Dept of Dermatology, University of Aachen Recruiting
Aachen, Germany, 52074
Principal Investigator: Hans F Merk, Prof. (MD)         
Dept of Dermatology, University of Berlin Charite Recruiting
Berlin, Germany, 10117
Principal Investigator: Uwe Trefzer, PD (MD)         
Dept of Dermatology, University of Bochum Recruiting
Bochum, Germany, 44791
Principal Investigator: Norbert Brockmeyer, Prof. (MD)         
Medizinisches Zentrum Bonn Friedensplatz Recruiting
Bonn, Germany, 53111
Principal Investigator: Uwe Reinhold, Prof. (MD)         
Dept of Dermatology, University of Essen Recruiting
Essen, Germany, 45147
Principal Investigator: Dirk Schadendorf, Prof. (MD)         
Dept of Dermatology, University of Frankfurt Recruiting
Frankfurt / Main, Germany, 60590
Principal Investigator: Roland Kaufmann, Prof. (MD)         
Dermatology, Klinikum Frankfurt/Oder Recruiting
Frankfurt/Oder, Germany, 15236
Principal Investigator: Anett Milling, Dr. (MD)         
Dept of Dermatology, University of Hannover Recruiting
Hannover, Germany, 30449
Principal Investigator: Ralf Gutzmer, PD (MD)         
Dept of Dermatology, Saarland University Recruiting
Homburg/Saar, Germany, 66421
Principal Investigator: Knuth Rass, Dr. (MD)         
Dept of Dermatology, University of Jena Recruiting
Jena, Germany, 07740
Principal Investigator: Martin Kaatz, Dr. (MD)         
Dept of Dermatology, University of Schleswig-Holstein Campus Kiel Recruiting
Kiel, Germany, 24105
Principal Investigator: Axel Hauschild, Prof. (MD)         
Dermatology, Klinikum Ludwishafen Recruiting
Ludwigshafen, Germany, 67063
Principal Investigator: Edgar Dippel, Prof. (MD)         
Dept of Dermatology, University of Schleswig-Holstein Campus Luebeck Recruiting
Luebeck, Germany, 23538
Principal Investigator: Patrick Terheyden, Dr. (MD)         
Dept of Dermatology, Univeristy of Magdeburg Recruiting
Magdeburg, Germany, 39120
Principal Investigator: Martin Leverkus, Prof. (MD)         
Dept of Dermatology, University of Mainz Recruiting
Mainz, Germany, 55131
Principal Investigator: Carmen Loquai, Dr. (MD)         
Dept of Dermatology, University of Mannheim Recruiting
Mannheim, Germany, 68167
Principal Investigator: Jessica Hassel, Dr. (MD)         
Dept of Dermatology, University of Marburg Recruiting
Marburg, Germany, 35033
Principal Investigator: Michael Hertl, Prof. (MD)         
Dept of Dermatology, University of Muenchen Recruiting
Muenchen, Germany, 80337
Principal Investigator: Carola Berking, Prof. (MD)         
Dept of Dermatology, University of Muenster Recruiting
Muenster, Germany, 48149
Principal Investigator: Cord Sunderkoetter, Prof. (MD)         
Dept of Medical Oncology, Fachklinik Hornheide Recruiting
Muenster, Germany, 48157
Principal Investigator: Michael Fluck, Dr. (MD)         
Dermatology, Klinikum Dorothea Christiane Erxleben Recruiting
Quedlinburg, Germany, 06484
Principal Investigator: Jens Ulrich, PD (MD)         
Dept of Dermatology, University of Tuebingen Recruiting
Tuebingen, Germany, 72086
Principal Investigator: Claus Garbe, Prof. (MD)         
Dept of Dermatology, University of Wuerzburg Recruiting
Wuerzburg, Germany, 97080
Principal Investigator: Selma Ugurel, Prof. (MD)         
Sponsors and Collaborators
University of Wuerzburg
Hiege-Stiftung gegen Hautkrebs
medac GmbH
DCS Innovative Diagnostik Systeme
Investigators
Study Chair: Selma Ugurel, Prof. (MD) Dept of Dermatology, University of Wuerzburg
  More Information

Additional Information:
Publications:
Responsible Party: Prof. Dr. med. Selma Ugurel, Dept of Dermatology, University of Wuerzburg
ClinicalTrials.gov Identifier: NCT00779714     History of Changes
Other Study ID Numbers: 101.321-13/07, EudraCT Nr. 2008-001686-28
Study First Received: October 22, 2008
Last Updated: October 22, 2008
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Wuerzburg:
metastatic (AJCC stage IV)
first-line chemotherapy
ex-vivo chemosensitivity profiling
evaluation of biomarkers

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Paclitaxel
Treosulfan
Cisplatin
Cytarabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 18, 2014