Clinical trial NCT01149343: Evaluation of a New Vaccine Treatment for Patients With Metastatic Skin Cancer
Official title: Study of GSK2302025A Antigen-Specific Cancer Immunotherapeutic in Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: PRAME
Cancer immunotherapeutic
Malignant melanoma
ASCI (Antigen-Specific Cancer Immunotherapeutic)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-06-23
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical study is to examine the safety, immunogenicity and clinical activity of the immunotherapeutic product GSK2302025A (also referred to as recPRAME + AS15 Antigen-Specific Cancer Immunotherapeutic \[ASCI\]) administered as a first line treatment in patients with unresectable and progressive metastatic cutaneous melanoma.

Detailed description: In this study, patients were to receive a maximum of 24 doses of recMAGE-A3 + AS15 according to four cycles over a period of four years. An active follow-phase (up to five years after registration into the study) was planned for all patients.

This protocol summary has been impacted by protocol amendment 3, so there will no longer be an active follow-up of patients after discontinuation or completion of the study treatment. The study will end approximately 30 days after the last dose will be administered.

In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant.

Sampling for safety monitoring as per protocol will continue.

Eligibility criteria: Inclusion Criteria:

1. Male or female patient with histologically proven cutaneous melanoma. Phase I segment: All melanoma patients with stage IV M1b and stage IV M1c including completely resected stage IV patients but with the exception of stage IV M1c disease with serum lactate dehydrogenase \> 1.5 x Upper Limit of Normal or with involvement of the Central Nervous System.

   Phase II segment: All melanoma patients with measurable, unresectable stage III melanoma including in-transit metastasis (with (N3) or without (N2c) nodal metastasis) and stage IV M1a melanoma. The patient should have documented progressive disease within 12 weeks of registration into the trial. Patients with resected stage IV and with stage IV M1b or M1c disease cannot be included.
2. Written informed consent for PRAME expression screening and gene profiling on resected tumor tissue and for the complete study has been obtained from the patient prior to shipment of the sample for expression testing and prior to the performance of any other protocol-specific procedure.
3. The patient is \>= 18 years old at the time of signing the first informed consent form.
4. The patient's tumor shows expression of the PRAME antigen as determined by RT-PCR analysis or any updated technique on fresh tissue sample.
5. Eastern Cooperative Oncology Group performance status of 0 or 1.
6. The patient has adequate bone marrow reserve, renal, adrenal and hepatic function as assessed by standard laboratory criteria.
7. Female patients of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause.
8. Female patients of childbearing potential may be enrolled in the study, if the patient:

   * has practiced adequate contraception for 30 days prior to the study product administration, and
   * has a negative pregnancy test on the day of administration, and
   * has agreed to continue adequate contraception during the entire treatment period and for 2 months after the completion of the study product administration series.
9. In the view of the investigator, the patient can and will comply with all the requirements of the protocol.

Exclusion Criteria:

1. The patient has at any time received systemic chemotherapy, (bio)-chemotherapy or CTLA-4 monoclonal antibodies for metastatic disease.
2. The patient is scheduled to receive any other anticancer treatment, including but not limited to (bio)-chemotherapeutic or immunomodulating agents and radiotherapy.
3. The patient has received any cancer immunotherapy containing the PRAME antigen or any cancer immunotherapy for his/her metastatic disease.
4. The patient requires concomitant treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents.
5. Use of any investigational or non-registered product (drug or vaccine) other than the study product within the 30 days preceding the first ASCI dose injection or planned use during the study period
6. The patient has (had) previous or concomitant malignancies at other sites (including carcinoma in situ), except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
7. The patient has an allergy to any component of the study investigational product or has a history of previous allergic reactions to vaccinations.
8. The patient has a history of confirmed adrenal dysfunction.
9. The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease.
10. The patient is known to be positive for the human immunodeficiency virus (HIV).
11. The patient has an uncontrolled bleeding disorder.
12. The patient has a family history of congenital or hereditary immunodeficiency.
13. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
14. The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
15. For female patients: the patient is pregnant or lactating.

Primary outcomes:
measure: Number of Patients With Dose-limiting Toxicity (Phase I)
timeFrame: During the study treatment (up to Year 4), for all patients
measure: Percentage of Patients With Anti-PReferentially Expressed Antigen of MElanoma (Anti-PRAME) Humoral Immune Response (Phase I)
timeFrame: After the administration of dose 4, at Week 8
measure: Number of Patients With Best Overall Response to Study Treatment (Phase II)
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
Secondary outcomes:
measure: Number of Patients With Any Unsolicited Adverse Events (AEs), by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Serious Adverse Events (SAEs), by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Laboratory Abnormalities Versus Baseline, by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Laboratory Abnormal Results Versus Baseline, by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Hematological and Biochemical Abnormalities Versus Baseline, by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Laboratory Hematological and Biochemical Abnormalities Versus Baseline, by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Lab Hematological and Biochemical Abnormalities Versus Baseline, by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Abnormal Hematological and Biochemical Results Versus Baseline, by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Number of Patients With Abnormal Hematological and Biochemical Laboratory Results Versus Baseline, by Maximum Grading
timeFrame: During the entire study period - up to Year 4 + 1 month post last study treatment administration
measure: Percentage of Patients With Anti-PRAME Cellular (T-cell) Response (Phase I)
timeFrame: Up to Data Lock Point at Week 8
measure: Number of Patients With Anti-PRAME Humoral Immune Response (Phase I & II)
timeFrame: At Weeks 0, 4, 8, 10, 12, 29, 51, 75, 99, 123, 147 and conclusion visit at 30 days post last treatment administration (Week 199) for each patient
measure: Number of Patients With Stable Disease (SD), Progressive Disease (PD), Mixed Response (MR) (Phase I & II)
timeFrame: At 30 days after the last treatment administration for each patient (Week 199)
measure: Number of Patients With Best Overall Response, Including Mixed Response (MxR) and Slow Progressive Disease (SPD) Criteria (Phase I & II)
timeFrame: At 30 days after the last treatment administration for each patient (Week 199)
measure: Anti-Protein D Humoral Response (Phase I & II)
timeFrame: At Week 0, 4, 8, 12, 29, 51, 75, 99, 123, 147, 30 days after the last treatment administration for each patient (Week 199), with follow-up, 3, 6, 9 and 12 months after concluding visit
measure: Anti-Cytosine Phosphate Guanosine Oligodeoxynucleotide (CpG) Humoral Response (Phase I & II)
timeFrame: At Week 0, 4, 8, 12, 29, 51, 75, 99, 123, 147, 30 days after the last treatment administration for each patient (Week 199), with follow-up, 3, 6, 9 and 12 months after concluding visit
measure: Time to Treatment Failure, Progression Free Survival and Overall Survival (Phase I & II)
timeFrame: Up to concluding visit, at Week 199
measure: Duration of Response for Patients With CR, PR and SD or SD/PR Status (Phase II)
timeFrame: Up to concluding visit, at Week 199
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Praha 2
country: Czechia
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Marseille cedex 5
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Reims
country: France
facility: GSK Investigational Site
city: Rennes
country: France
facility: GSK Investigational Site
city: Vandoeuvre les Nancy
country: France
facility: GSK Investigational Site
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Nuernberg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Homburg
country: Germany
facility: GSK Investigational Site
state: Saarland
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Jena
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Meldola (FC)
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Rimini
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Rozzano (MI)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Slupsk
country: Poland
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Pyatigorsk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gutzmer R, Rivoltini L, Levchenko E, Testori A, Utikal J, Ascierto PA, Demidov L, Grob JJ, Ridolfi R, Schadendorf D, Queirolo P, Santoro A, Loquai C, Dreno B, Hauschild A, Schultz E, Lesimple TP, Vanhoutte N, Salaun B, Gillet M, Jarnjak S, De Sousa Alves PM, Louahed J, Brichard VG, Lehmann FF. Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study. ESMO Open. 2016 Aug 8;1(4):e000068. doi: 10.1136/esmoopen-2016-000068. eCollection 2016.