Clinical trial NCT00991250: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Malignant Melanoma
Keywords: Malignant melanoma
Lead sponsor: SentoClone AB
Sponsor class: INDUSTRY
First posted: 2009-10-07
Enrollment: 140
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: At baseline and 18, 26 and 34 weeks after treatment
Secondary outcomes:
measure: Progression-free survival
timeFrame: From baseline to week 34 after initiated treatment
measure: Overall survival
timeFrame: From baseline to week 34 after initiated treatment
measure: Time to tumour progression
timeFrame: From baseline to week 34 after initiated treatment
measure: Disease-free survival
timeFrame: From baseline to week 34 after initiated treatment
measure: Time to treatment failure
timeFrame: From baseline to week 34 after initiated treatment
measure: Duration of response
timeFrame: From baseline to week 34 after initiated treatment
measure: Correlation between tumour response and tumour marker S100
timeFrame: From baseline to week 34 after initiated treatment
measure: Proportion of patients showing toxic symptoms according to CTCAE criteria
timeFrame: From baseline to week 34 after initiated treatment
measure: Quality of life (EQ-5D and QLQ-C30)
timeFrame: From baseline to week 34 after initiated treatment
measure: Adverse Events (AEs) classified according to seriousness, causality, and intensity, clinically significant deviations in vital signs, clinical chemistry, and haematology
timeFrame: From baseline to week 34 after initiated treatment
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Lunds Universitetssjukhus
state: Skåne
city: Stockholm
country: Sweden
facility: Södersjukhuset
state: Stockholms Län
city: Stockholm
country: Sweden
facility: Karolinska Sjukhuset
state: Stockholms Län
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
state: Västerbottens Län
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
state: Västra Götalands Län
Study officials:
affiliation: Lund University Hospital
name: Christian Ingvar, MD
role: PRINCIPAL_INVESTIGATOR
References: