SentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by SentoClone AB.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
SentoClone AB
ClinicalTrials.gov Identifier:
NCT00991250
First received: October 5, 2009
Last updated: February 4, 2010
Last verified: February 2010
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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
Experimental: SentoClone®
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.
Active Comparator: Temodal® or Dacarbazine Medac®

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

  1. Temodal® (temozolomide)
  2. 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.

Other Names:
  • DTIC
  • Dacarbazine
  • Temozolomide

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:

  1. Surgically incurable stage III or IV malignant melanoma
  2. At least one measurable lesion
  3. WHO performance status 0-1
  4. Life expectancy > 3 months
  5. Diagnosed metastasis
  6. One tumour draining lymph node surgically accessible
  7. Measurable tumour manifestation after the harvest of tumour tissue and sentinel/metinel nodes(1)
  8. 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

  1. 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
  2. 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
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: NCT00991250

Locations
Sweden
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         
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         
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         
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: Freddi Lewin, Medical director, SentoClone AB
ClinicalTrials.gov Identifier: NCT00991250     History of Changes
Other 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
Health Authority: Sweden: Medical Products Agency

Keywords provided by SentoClone AB:
Malignant melanoma

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
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014