SentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma - Full Text View

Sponsor:	SentoClone AB
Information provided by:	SentoClone AB
ClinicalTrials.gov Identifier:	NCT00991250

Purpose

The purpose of this study is to elucidate whether SentoClone® gives improved treatment responses in patients with advanced malignant melanoma in comparison to established reference treatment(s).

Condition	Intervention	Phase
Malignant Melanoma	Biological: SentoClone® Drug: Temodal® or Dacarbazine Medac®	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	A Multi-centre, Two-arm, Randomized, Open, Phase II Study Investigating SentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Temozolomide Dacarbazine

U.S. FDA Resources

Further study details as provided by SentoClone AB:

Primary Outcome Measures:

Tumour response rate, defined as complete response (CR) or partial response (PR) (i.e. at least partial response) measured using the RECIST (Response Evaluation Criteria in Solid Tumours) criteria. [ Time Frame: At baseline and 18, 26 and 34 weeks after treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Progression-free survival [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Overall survival [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Time to tumour progression [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Disease-free survival [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Time to treatment failure [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Duration of response [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Correlation between tumour response and tumour marker S100 [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Proportion of patients showing toxic symptoms according to CTCAE criteria [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Quality of life (EQ-5D and QLQ-C30) [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]
Adverse Events (AEs) classified according to seriousness, causality, and intensity, clinically significant deviations in vital signs, clinical chemistry, and haematology [ Time Frame: From baseline to week 34 after initiated treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	140
Study Start Date:	October 2009
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
SentoClone®: Experimental SentoClone®: Specific tumour-reactive lymphocytes located in lymph nodes directly draining primary tumours or metastases are identified and expanded. These lymphocytes are infused to the patient to treat metastatic disease.	Biological: SentoClone® SentoClone® are autologous tumour-reactive lymphocytes which are expanded and infused to the patient, where they have the opportunity to seek out and attack the primary tumour and metastases. The first step is to identify the tumour draining lymph node(s), which is done in parallel to surgical resection of the primary tumour or metastasis. The sentinel and/or metinel node(s), the initial meeting place between tumour antigen and the immune system, are further dissected and collected during the surgery. The lymphocytes are extracted from the collected lymph nodes and expanded in vitro, the lymphocytes are thereafter stimulated with tumour extract and returned to the patient intravenously as an autologous cell transfusion. The administered volume will be 100 ml for cell densities less than 3x106 cells/ml and 200 ml for cell densities of 3x106 cells/ml or more.
Temodal® or Dacarbazine Medac®: Active Comparator To be decided by each centre as one of the following: Temodal® (temozolomide) Dacarbazine Medac® (dacarbazine) The reference treatment regimen should follow the general guiding principles for each of the two reference treatments.	Drug: Temodal® or Dacarbazine Medac® Dacarbazine (5-[3,3-Dimethyl-1-triazenyl]imidazole-4-carboxamide) is a widely used systemic treatment against advanced malignant melanoma. Dacarbazine is a cytostatic agent, which inhibits tumour growth by interfering with DNA-synthesises. The DNA-synthesis is inhibited by alkylation of the DNA molecule; however, it is unclear whether dacarbazine has other cytostatic impacts on cell mechanisms. Dacarbazine is inactive until liver passage, the liver converts dacarbazine to its reactive metabolites MTIC and HMMTIC, which alkylate DNA. Dacarbazine is light sensitive and needs to be administered intravenously. A newer analogue to dacarbazine, temozolomide (Temodal®), has been developed for oral administration. Temodal® is administered in capsules and is rapidly absorbed reaching peak concentrations after 20 minutes. Temodal® is converted to MTIC at physiological pH, the same reactive molecule as dacarbazine is metabolized to in the liver.

Arms

Assigned Interventions

SentoClone®: Experimental

SentoClone®: Specific tumour-reactive lymphocytes located in lymph nodes directly draining primary tumours or metastases are identified and expanded. These lymphocytes are infused to the patient to treat metastatic disease.

Biological: SentoClone®

SentoClone® are autologous tumour-reactive lymphocytes which are expanded and infused to the patient, where they have the opportunity to seek out and attack the primary tumour and metastases. The first step is to identify the tumour draining lymph node(s), which is done in parallel to surgical resection of the primary tumour or metastasis. The sentinel and/or metinel node(s), the initial meeting place between tumour antigen and the immune system, are further dissected and collected during the surgery. The lymphocytes are extracted from the collected lymph nodes and expanded in vitro, the lymphocytes are thereafter stimulated with tumour extract and returned to the patient intravenously as an autologous cell transfusion. The administered volume will be 100 ml for cell densities less than 3x106 cells/ml and 200 ml for cell densities of 3x106 cells/ml or more.

Temodal® or Dacarbazine Medac®: Active Comparator

To be decided by each centre as one of the following:

Temodal® (temozolomide)
Dacarbazine Medac® (dacarbazine) The reference treatment regimen should follow the general guiding principles for each of the two reference treatments.

Drug: Temodal® or Dacarbazine Medac®

Dacarbazine (5-[3,3-Dimethyl-1-triazenyl]imidazole-4-carboxamide) is a widely used systemic treatment against advanced malignant melanoma. Dacarbazine is a cytostatic agent, which inhibits tumour growth by interfering with DNA-synthesises. The DNA-synthesis is inhibited by alkylation of the DNA molecule; however, it is unclear whether dacarbazine has other cytostatic impacts on cell mechanisms. Dacarbazine is inactive until liver passage, the liver converts dacarbazine to its reactive metabolites MTIC and HMMTIC, which alkylate DNA. Dacarbazine is light sensitive and needs to be administered intravenously.

A newer analogue to dacarbazine, temozolomide (Temodal®), has been developed for oral administration. Temodal® is administered in capsules and is rapidly absorbed reaching peak concentrations after 20 minutes. Temodal® is converted to MTIC at physiological pH, the same reactive molecule as dacarbazine is metabolized to in the liver.

Detailed Description:

Malignant melanoma is one of the most common cancer forms worldwide and WHO estimates 132,000 new cases each year. The incidence rate vary up to 150-fold between different regions and ethnicities, the highest rates are found in emigrated Caucasian populations (e.g. Australia and New Zealand).

There are few therapy alternatives for advanced malignant melanomas. At present, dacarbazine (Dacarbazine Medac®) is the most commonly used therapy. Immunotherapy with IL-2 and IFN is an alternative, but it is associated with multiple side effects. Hence, there remains a considerable need for alternative treatments.

By using SentoClone®, autologous tumour-reactive lymphocytes are expanded and infused to the patient, where they have the opportunity to seek out and attack the primary tumour and metastases. The first step is to identify the tumour draining lymph node(s), which is done in parallel to surgical resection of the primary tumour or metastasis. The sentinel and/or metinel node(s), the initial meeting place between tumour antigen and the immune system, are further dissected and collected during the surgery.

In this study SentoClone® will be compared with Dacarbazine Medac® and Temodal® which are currently regarded as standard first-line therapies in advanced malignant melanoma.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

To be eligible for inclusion in this study, the patients must fulfil all of the following criteria:

Surgically incurable stage III or IV malignant melanoma
At least one measurable lesion
WHO performance status 0-1
Life expectancy > 3 months
Diagnosed metastasis
One tumour draining lymph node surgically accessible
Measurable tumour manifestation after the harvest of tumour tissue and sentinel/metinel nodes(1)
Signed informed consent

(1) Should be fulfilled after surgery (visit 2) for patients randomised to SentoClone®.

Exclusion Criteria

To be eligible for inclusion in this study the patients must not meet any of the following criteria:

1. Known allergy against used trace substance patent blue and/or albumin technetium (Nanocoll) 2. Known allergy against gentamicin and/or phenol red 3. Any condition (medical, social, psychological or legal) that influences adequate information negatively or is considered to be a problem for the patient to cope with treatment and follow-up 4. Aplastic anaemia or myelofibrosis 5. Previous treatment with temozolomide or dacarbazine, or any other chemotherapy during the last 3 months 6. Disease progression following treatment with temozolomide or dacarbazine more than 3 months back(1) 7. Previous radiotherapy of target lesion(s) or tumour draining lymph nodes which will be used for lymphocyte extraction(2) 8. Ongoing systemic steroid treatment or other treatment influencing immune defence 9. History of other malignant tumour disease apart from adequately treated basalioma or squamous cell carcinoma of the skin more than 5 years ago 10. Positive test(s) for HIV and/or Hepatitis B and/or Hepatitis C and/or syphilis 11. Condition or disease which could influence the result of the study or which indicates that the patient runs risks by participating in this study 12. Participation in any other clinical study, involving other investigational methods or products that may influence the results of this trial, within 30 days prior to participating in this trial

Patients who responded on the treatment, terminated the treatment at least 3 months prior to the study, and later progressed do not fulfill exclusion criterion 6
Irradiated lesions are not considered to be measurable and are therefore not suitable as target lesions. Lesions which have been irradiated but shown progression are considered as measurable.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00991250

Locations

Sweden, Skåne
Lunds Universitetssjukhus	Recruiting
Lund, Skåne, Sweden, 22185
Contact: Christian Ingvar, MD +46 (0)46-17 10 00 christian.ingvar@skane.se
Principal Investigator: Christian Ingvar, MD
Sweden, Stockholms Län
Södersjukhuset	Recruiting
Stockholm, Stockholms Län, Sweden, 11883
Contact: Peter Gillgren, MD +46 (0)8-616 23 84 peter.gillgren@sodersjukhuset.se
Principal Investigator: Peter Gillgren, MD
Karolinska Sjukhuset	Recruiting
Stockholm, Stockholms Län, Sweden, 17176
Contact: Johan Hansson, MD +46 (0)8-5177 36 40 johan.hansson@karolinska.se
Principal Investigator: Johan Hansson, MD
Sweden, Västerbottens Län
Norrlands Universitetssjukhus	Recruiting
Umeå, Västerbottens Län, Sweden, 90185
Contact: Peter Naredi, MD +46 (0)90- 785 00 00 peter.naredi@surgery.umu.se
Principal Investigator: Peter Naredi, MD
Sweden, Västra Götalands Län
Sahlgrenska Universitetssjukhuset	Not yet recruiting
Göteborg, Västra Götalands Län, Sweden, 41685
Contact: Jan E Mattsson, MD +46 (0)31-342 84 58 jan.e.mattsson@vgregion.se
Principal Investigator: Jan E Mattsson, MD

Sponsors and Collaborators

SentoClone AB

Investigators

Principal Investigator:

Christian Ingvar, MD

Lund University Hospital

More Information

No publications provided

Responsible Party:	SentoClone AB ( Freddi Lewin, Medical director )
Study ID Numbers:	Mel-Swe-01 2009-12-17, EudraCT No: 2008-007515-33
Study First Received:	October 5, 2009
Last Updated:	February 4, 2010
ClinicalTrials.gov Identifier:	NCT00991250 History of Changes
Health Authority:	Sweden: Medical Products Agency

Keywords provided by SentoClone AB:

Malignant melanoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Dacarbazine
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Temozolomide
Pharmacologic Actions
Melanoma

Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on February 08, 2010