Evaluation of a New Vaccine Treatment for Patients With Metastatic Skin Cancer

NCT01149343 | Completed Phase 1 Results

• 2 other identifiers: 1131732009-016636-13
• Study Type: interventional
• Target: 107
• Locations: 6 countries
• Sites: 37

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.

Conditions

Melanoma

Keywords

PRAME; Cancer immunotherapeutic; Malignant melanoma; ASCI (Antigen-Specific Cancer Immunotherapeutic)

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Dose-limiting Toxicity (Phase I)

  The dose-limiting toxicities (DLT) were defined as follows: •An Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly ASCI related grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) persisting for 48 hours despite therapy. •An ASCI related or possibly ASCI related grade 2 or higher allergic reaction occurring within 24 hours following the ASCI administration. •An ASCI related or possibly ASCI related decrease in renal function, with a creatinine clearance lower than (\<) 40 milliliters per minute (mL/min). •An ASCI-related or possibly ASCI-related symptomatic and confirmed adrenal insufficiency. The grading used was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 3 DLT = severe DLT. Related = DLT considered by investigator as possibly related to product administration.

  During the study treatment (up to Year 4), for all patients

• Percentage of Patients With Anti-PReferentially Expressed Antigen of MElanoma (Anti-PRAME) Humoral Immune Response (Phase I)

  A seronegative/seropositive patient for anti-PRAME antibodies was a patient with antibody concentration lower (\<)/ higher than or equal to (≥) cut-off level. Humoral immune response was defined as a) if baseline concentration \< cut-off level: post treatment concentration ≥ cut-off level, or b) if baseline concentration ≥ cut-off level: post treatment concentration at least twice the baseline value. Cut-off values for seropositivity (by enzyme-linked immunosorbent assay \[ELISA\]) were 12 ELISA Units per milliliter (EL.U/mL).

  After the administration of dose 4, at Week 8

• Number of Patients With Best Overall Response to Study Treatment (Phase II)

  The best overall response is the best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). In general the patient's best response assignment depended on the achievement of both measurement and confirmation criteria. The best overall response includes the complete response (CR) defined as disappearance of all targeted/non-targeted lesions and partial response (PR) defined as at least 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD and persistence of one or more non-targeted lesion(s).

  During the entire study period - up to Year 4 + 1 month post last study treatment administration

Secondary Outcomes (17)

• Number of Patients With Any Unsolicited Adverse Events (AEs), by Maximum Grading

  During the entire study period - up to Year 4 + 1 month post last study treatment administration

• Number of Patients With Serious Adverse Events (SAEs), by Maximum Grading

  During the entire study period - up to Year 4 + 1 month post last study treatment administration

• Number of Patients With Laboratory Abnormalities Versus Baseline, by Maximum Grading

  During the entire study period - up to Year 4 + 1 month post last study treatment administration

• Number of Patients With Laboratory Abnormal Results Versus Baseline, by Maximum Grading

  During the entire study period - up to Year 4 + 1 month post last study treatment administration

• Number of Patients With Hematological and Biochemical Abnormalities Versus Baseline, by Maximum Grading

  During the entire study period - up to Year 4 + 1 month post last study treatment administration

Study Arms (4)

GSK2302025A Cohort 1

EXPERIMENTAL

Male or female patients with histologically proven cutaneous melanoma received the investigational Low-Dose (LD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.

Biological: Immunotherapeutic GSK2302025A, different formulations

GSK2302025A Cohort 2

EXPERIMENTAL

Male or female patients with histologically proven cutaneous melanoma received the investigational Middle-Dose (MD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.

Biological: Immunotherapeutic GSK2302025A, different formulations

GSK2302025A Cohort 3

EXPERIMENTAL

Male or female patients with histologically proven cutaneous melanoma received the investigational High-Dose (HD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.

Biological: Immunotherapeutic GSK2302025A, different formulations

GSK2302025A Cohort 4

EXPERIMENTAL

In Phase 2 of the study subjects received the optimal investigational dose-level identified in Phase 1. Patients received a treatment consisting of 24 injections of the experimental GSK2302025A immunotherapeutic.

Biological: Immunotherapeutic GSK2302025A, different formulations

Interventions

Immunotherapeutic GSK2302025A, different formulations BIOLOGICAL

Intramuscular administration

Also known as: PRAME ASCI

GSK2302025A Cohort 1; GSK2302025A Cohort 2; GSK2302025A Cohort 3; GSK2302025A Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• The patient is \>= 18 years old at the time of signing the first informed consent form.
• The patient's tumor shows expression of the PRAME antigen as determined by RT-PCR analysis or any updated technique on fresh tissue sample.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• The patient has adequate bone marrow reserve, renal, adrenal and hepatic function as assessed by standard laboratory criteria.
• 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.
• 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.
• In the view of the investigator, the patient can and will comply with all the requirements of the protocol.

You may not qualify if:

• The patient has at any time received systemic chemotherapy, (bio)-chemotherapy or CTLA-4 monoclonal antibodies for metastatic disease.
• The patient is scheduled to receive any other anticancer treatment, including but not limited to (bio)-chemotherapeutic or immunomodulating agents and radiotherapy.
• The patient has received any cancer immunotherapy containing the PRAME antigen or any cancer immunotherapy for his/her metastatic disease.
• The patient requires concomitant treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents.
• 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
• 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.
• The patient has an allergy to any component of the study investigational product or has a history of previous allergic reactions to vaccinations.
• The patient has a history of confirmed adrenal dysfunction.
• The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease.
• The patient is known to be positive for the human immunodeficiency virus (HIV).
• The patient has an uncontrolled bleeding disorder.
• The patient has a family history of congenital or hereditary immunodeficiency.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
• 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.
• For female patients: the patient is pregnant or lactating.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (37)

GSK Investigational Site

Brno, 656 53, Czechia

Location

GSK Investigational Site

Hradec Králové, 500 05, Czechia

Location

GSK Investigational Site

Prague, 128 08, Czechia

Location

GSK Investigational Site

Bordeaux, 33075, France

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Marseille, 13385, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Reims, 51092, France

Location

GSK Investigational Site

Rennes, 35042, France

Location

GSK Investigational Site

Vandœuvre-lès-Nancy, 54511, France

Location

GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

GSK Investigational Site

Nuremberg, Bavaria, 90419, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Homburg, Saarland, 66421, Germany

Location

GSK Investigational Site

Kiel, Schleswig-Holstein, 24105, Germany

Location

GSK Investigational Site

Lübeck, Schleswig-Holstein, 23538, Germany

Location

GSK Investigational Site

Jena, Thuringia, 07740, Germany

Location

GSK Investigational Site

Berlin, 13585, Germany

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

Meldola (FC), Emilia-Romagna, 47014, Italy

Location

GSK Investigational Site

Ravenna, Emilia-Romagna, 48100, Italy

Location

GSK Investigational Site

Rimini, Emilia-Romagna, 47900, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20133, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Rozzano (MI), Lombardy, 20089, Italy

Location

GSK Investigational Site

Gdansk, 80-215, Poland

Location

GSK Investigational Site

Poznan, 60-693, Poland

Location

GSK Investigational Site

Słupsk, 76-200, Poland

Location

GSK Investigational Site

Chelyabinsk, 454087, Russia

Location

GSK Investigational Site

Moscow, 115478, Russia

Location

GSK Investigational Site

Pyatigorsk, 357502, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

GSK Investigational Site

Saint Petersburg, Russia

Location

Related Publications (1)

• 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.

  PMID: 27843625 DERIVED

MeSH Terms

Conditions

Melanoma; Atypical Squamous Cells of the Cervix

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Cervical Dysplasia; Precancerous Conditions; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

As a consequence of the decision to stop the study, not all data are available for a full final analysis as originally planned. Analyses are merely descriptive and the results are presented as an abridged study report.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2010
• First Posted: June 23, 2010
• Study Start: July 2, 2010
• Primary Completion: February 11, 2014
• Study Completion: December 19, 2016
• Last Updated: November 20, 2020
• Results First Posted: August 31, 2018

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

PL (3); RU (5); FR (7); IT (8); CZ (3); DE (11)