Back to resultsSentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma
Primary Purpose
Malignant Melanoma
Status
Unknown status
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
SentoClone®
Temodal® or Dacarbazine Medac®
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Melanoma focused on measuring Malignant melanoma
Eligibility 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.
Sites / Locations
- Lunds UniversitetssjukhusRecruiting
- SödersjukhusetRecruiting
- Karolinska SjukhusetRecruiting
- Norrlands UniversitetssjukhusRecruiting
- Sahlgrenska Universitetssjukhuset
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
SentoClone®
Temodal® or Dacarbazine Medac®
Arm Description
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.
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.
Outcomes
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.
Secondary Outcome Measures
Progression-free survival
Overall survival
Time to tumour progression
Disease-free survival
Time to treatment failure
Duration of response
Correlation between tumour response and tumour marker S100
Proportion of patients showing toxic symptoms according to CTCAE criteria
Quality of life (EQ-5D and QLQ-C30)
Adverse Events (AEs) classified according to seriousness, causality, and intensity, clinically significant deviations in vital signs, clinical chemistry, and haematology
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00991250
Brief Title
SentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma
Official Title
A Multi-centre, Two-arm, Randomized, Open, Phase II Study Investigating SentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2010
Overall Recruitment Status
Unknown status
Study Start Date
October 2009 (undefined)
Primary Completion Date
September 2011 (Anticipated)
Study Completion Date
September 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
SentoClone AB
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
Keywords
Malignant melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SentoClone®
Arm Type
Experimental
Arm Description
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.
Arm Title
Temodal® or Dacarbazine Medac®
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
SentoClone®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Temodal® or Dacarbazine Medac®
Other Intervention Name(s)
DTIC, Dacarbazine, Temozolomide
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
From baseline to week 34 after initiated treatment
Title
Overall survival
Time Frame
From baseline to week 34 after initiated treatment
Title
Time to tumour progression
Time Frame
From baseline to week 34 after initiated treatment
Title
Disease-free survival
Time Frame
From baseline to week 34 after initiated treatment
Title
Time to treatment failure
Time Frame
From baseline to week 34 after initiated treatment
Title
Duration of response
Time Frame
From baseline to week 34 after initiated treatment
Title
Correlation between tumour response and tumour marker S100
Time Frame
From baseline to week 34 after initiated treatment
Title
Proportion of patients showing toxic symptoms according to CTCAE criteria
Time Frame
From baseline to week 34 after initiated treatment
Title
Quality of life (EQ-5D and QLQ-C30)
Time Frame
From baseline to week 34 after initiated treatment
Title
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
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Ingvar, MD
Organizational Affiliation
Lund University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lunds Universitetssjukhus
City
Lund
State/Province
Skåne
ZIP/Postal Code
22185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Ingvar, MD
Phone
+46 (0)46-17 10 00
Email
christian.ingvar@skane.se
First Name & Middle Initial & Last Name & Degree
Christian Ingvar, MD
Facility Name
Södersjukhuset
City
Stockholm
State/Province
Stockholms Län
ZIP/Postal Code
11883
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Gillgren, MD
Phone
+46 (0)8-616 23 84
Email
peter.gillgren@sodersjukhuset.se
First Name & Middle Initial & Last Name & Degree
Peter Gillgren, MD
Facility Name
Karolinska Sjukhuset
City
Stockholm
State/Province
Stockholms Län
ZIP/Postal Code
17176
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan Hansson, MD
Phone
+46 (0)8-5177 36 40
Email
johan.hansson@karolinska.se
First Name & Middle Initial & Last Name & Degree
Johan Hansson, MD
Facility Name
Norrlands Universitetssjukhus
City
Umeå
State/Province
Västerbottens Län
ZIP/Postal Code
90185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Naredi, MD
Phone
+46 (0)90- 785 00 00
Email
peter.naredi@surgery.umu.se
First Name & Middle Initial & Last Name & Degree
Peter Naredi, MD
Facility Name
Sahlgrenska Universitetssjukhuset
City
Göteborg
State/Province
Västra Götalands Län
ZIP/Postal Code
41685
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan E Mattsson, MD
Phone
+46 (0)31-342 84 58
Email
jan.e.mattsson@vgregion.se
First Name & Middle Initial & Last Name & Degree
Jan E Mattsson, MD
12. IPD Sharing Statement
Learn more about this trial
SentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma
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