AzTrials
AzTrials

MelanomaPhase 3ChemoSensMMNCT00779714

Comparative Study of Individualized Sensitivity-Directed Chemotherapy Versus DTIC

A Phase 3 study testing DTIC (dacarbazine), paclitaxel + cisplatin and treosulfan + cytarabine in people with Melanoma, run by University of Wuerzburg at 23 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
DTIC (dacarbazine), paclitaxel + cisplatin and treosulfan + cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
360 participants
Where
23 sitesGermany
Study dates
Oct 2008to Apr 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 21Show fewer
  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

23 sites in 1 country.

Selma Ugurel, Prof. (MD) contact

0049931201 ext. 26118

Ugurel_S@klinik.uni-wuerzburg.de

23 sites in 1 country

Germany23 sites, 23 recruiting

  • Dept of Dermatology, University of Aachen

    Aachen, 52074

    Hans F Merk, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Berlin Charite

    Berlin, 10117

    Uwe Trefzer, PD (MD)

    Recruiting

  • Dept of Dermatology, University of Bochum

    Bochum, 44791

    Norbert Brockmeyer, Prof. (MD)

    Recruiting

  • Medizinisches Zentrum Bonn Friedensplatz

    Bonn, 53111

    Uwe Reinhold, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Essen

    Essen, 45147

    Dirk Schadendorf, Prof. (MD)

    Recruiting

  • Dermatology, Klinikum Frankfurt/Oder

    Frankfurt (Oder), 15236

    Anett Milling, Dr. (MD)

    Recruiting

  • Dept of Dermatology, University of Frankfurt

    Frankfurt am Main, 60590

    Roland Kaufmann, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Hannover

    Hanover, 30449

    Ralf Gutzmer, PD (MD)

    Recruiting

  • Dept of Dermatology, Saarland University

    Homburg/Saar, 66421

    Knuth Rass, Dr. (MD)

    Recruiting

  • Dept of Dermatology, University of Jena

    Jena, 07740

    Martin Kaatz, Dr. (MD)

    Recruiting

  • Dept of Dermatology, University of Schleswig-Holstein Campus Kiel

    Kiel, 24105

    Axel Hauschild, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Schleswig-Holstein Campus Luebeck

    Lübeck, 23538

    Patrick Terheyden, Dr. (MD)

    Recruiting

  • Dermatology, Klinikum Ludwishafen

    Ludwigshafen, 67063

    Edgar Dippel, Prof. (MD)

    Recruiting

  • Dept of Dermatology, Univeristy of Magdeburg

    Magdeburg, 39120

    Martin Leverkus, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Mainz

    Mainz, 55131

    Carmen Loquai, Dr. (MD)

    Recruiting

  • Dept of Dermatology, University of Mannheim

    Mannheim, 68167

    Jessica Hassel, Dr. (MD)

    Recruiting

  • Dept of Dermatology, University of Marburg

    Marburg, 35033

    Michael Hertl, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Muenchen

    München, 80337

    Carola Berking, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Muenster

    Münster, 48149

    Cord Sunderkoetter, Prof. (MD)

    Recruiting

  • Dept of Medical Oncology, Fachklinik Hornheide

    Münster, 48157

    Michael Fluck, Dr. (MD)

    Recruiting

  • Dermatology, Klinikum Dorothea Christiane Erxleben

    Quedlinburg, 06484

    Jens Ulrich, PD (MD)

    Recruiting

  • Dept of Dermatology, University of Tuebingen

    Tübingen, 72086

    Claus Garbe, Prof. (MD)

    Recruiting

  • Dept of Dermatology, University of Wuerzburg

    Würzburg, 97080

    Selma Ugurel, Prof. (MD)

    Recruiting

Other trials in Germany

About this study

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

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 ?
Read the 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).

Conditions
Melanoma
Being tested
DTIC (dacarbazine), paclitaxel + cisplatin, treosulfan + cytarabine
Keywords
metastatic (AJCC stage IV), first-line chemotherapy, ex-vivo chemosensitivity profiling, evaluation of biomarkers
Medical subject headings
Melanoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DTIC (dacarbazine)Drug

    Also called detimedac

    1000 mg/m2, d1 every 21 days

  • paclitaxel + cisplatinDrug

    Also called taxomedac + cisplatin medac

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

  • treosulfan + cytarabineDrug

    Also called ovastat + alexan

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

Study groups in NCT00779714
Study groupRoleWhat they receive
A (individualized combined chemotherapy)ExperimentalNot described
Receives: Drug: paclitaxel + cisplatin; Drug: treosulfan + cytarabine
B (DTIC monochemotherapy)Active comparatorNot described
Receives: Drug: DTIC (dacarbazine)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-specific overall survival

    Measured: 4 years

Secondary outcomes (1)

  1. Objective response

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2008 (estimated)
  2. Study startOct 2008
  3. Primary completionOct 2012 (estimated)
  4. Study completionApr 2013 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
360 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00779714
Sponsor's protocol ID
101.321-13/07
Other IDs
EudraCT Nr. 2008-001686-28
Acronym
ChemoSensMM
Status last verified
Oct 2008
First submitted
22 Oct 2008
Last updated
24 Oct 2008
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 17000680

  • 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.

    PubMed 12528801

  • 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.

    PubMed 10477162

  • 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.

    PubMed 7585588

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing DTIC (dacarbazine), paclitaxel + cisplatin and treosulfan + cytarabine in people with Melanoma, run by University of Wuerzburg at 23 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Selma Ugurel, Prof. (MD) (0049931201 ext. 26118, Ugurel_S@klinik.uni-wuerzburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-specific overall survival (time frame: 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00779714, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2008.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in