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A Phase II Randomised Trial of Three Regimens of GX301 Vaccination in Castration-resistant Prostate Cancer

Primary Purpose

Prostate Cancer

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

GX301

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Castration-resistant prostate cancer, Therapeutic vaccine, Telomerase vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Documented patient history

Histologically confirmed diagnosis of prostate cancer, with an available Gleason score.
Diagnosis of progressive, castration-resistant prostate cancer (CRPC), leading to inception of first-line chemotherapy with a docetaxel-based regimen.
Completion of chemotherapy with a cumulative delivered dose of 300 to 825 mg/m2 docetaxel.

Note: Pre-chemotherapy exposure to abiraterone and prednisone does not preclude eligibility, provided that both agents have been discontinued prior to initiation of docetaxel.

Current patient status

Ability to understand study-related patient information and provision of written informed consent for participation in the study.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Life expectancy of at least 6 months.
An interval ≥4 weeks elapsed from the last docetaxel administration.
Documented achievement of response or disease stability with docetaxel chemotherapy.
Absence of cancer-related symptoms suggesting clinical disease progression.
Current castrate testosterone level (≤50 ng/dL) due to current gonadotropin-releasing hormone (GnRH) agonist or antagonist therapy or past orchiectomy.
Haematology and blood chemistry tests within specified limits.
Successful recovery from acute toxicities from prior chemotherapy.
Confirmation from the immunology laboratory that the blood sample provided for baseline immunological tests is technically adequate.

Exclusion Criteria:

Known intolerance to Montanide or imiquimod.
Known presence of brain metastatic disease or spinal cord compression.
Radiotherapy within the past 4 weeks.
Concomitant presence of other primary malignancy
Major surgery within 4 weeks prior to randomisation.
Cardiovascular illness or complication which, in Investigator's judgment, compromises prognosis at 6 months or prevents the patient from following study procedures.
Serious uncontrolled infection.
Known presence of active autoimmune disease.
Known presence of acquired, hereditary, or congenital immunodeficiency.
HIV infection.
Current need for immunosuppressive drug therapy, including systemic corticosteroids.
Current need for denosumab therapy. (Patients under bisphosphonate treatment are eligible).
Skin disease interfering with evaluation of local tolerance of GX301 injections.
Participation in any interventional drug or medical device study within 30 days prior to treatment start.

Sites / Locations

S.C. di Oncologia, A.S.O. "Santi Antonio e Biagio e Cesare Arrigo"
Oncologia Medica A, Centro di Riferimento Oncologico (CRO)
Oncologia Medica, Azienda Ospedaliero Universitaria - Policlinico Consorziale
U.O.C. Urologia 1, A.O.U. Consorziale Policlinico di Bari
Oncologia Medica, A.O. Spedali Civili
S.C. Oncologia Medica, Presidio Ospedaliero Busto Arsizio
IRCCS Fondazione del Piemonte per l'Oncologia (FPO)
Clinica di Oncologia Medica, IRCCS San Martino-IST
U.O. Medicina Oncologica - Ospedale San Raffaele IRCCS
Unità Oncologica Medica Urogenitale, Istituto Europeo di Oncologia
Dipartimento Uro-Ginecologico, IRCCS Istituto Nazionale Tumori - Fondazione Pascale
U.O.C. di Oncologia Medica, A.O.R.N. "Antonio Cardarelli"
Oncologia Medica, A.O. Universitaria San Luigi Gonzaga
U.O. di Oncologia, AUSL di Piacenza
Unita Oncologica, Azienda Ospedaliera S. Maria degli Angeli
U.O.C. di Oncologia Medica, Policlinico "Le Scotte"
Oncologia Medica d.U., Policlinico G.B. Rossi, A.O.U.I. Verona
Medical Oncology, Hospital Vall d'Hebron
Hospital Clìnic i Provincial de Barcelona
Medical Oncology, Institut Català d'Oncologìa
Oncología, Hospital Universitario Gregorio Marañón
Servicio de Oncologìa Médica, Hospital Universitario Ramòn y Cajal
Oncología Médica, Hospital Clínico San Carlos
Oncology, Corporaciò Sanitària Parc Taulì

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

GX301 Regimen A (8 administrations)

GX301 Regimen B (4 administrations)

GX301 Regimen C (2 administrations)

Arm Description

Administration time frame: Day 1 to Day 63.

Outcomes

Primary Outcome Measures

Achievement of immunological response

Incidence of adverse events

Changes from baseline in laboratory tests for immunological safety

Secondary Outcome Measures

Changes from baseline in serum prostate-specific antigen (PSA)

Progression-free survival

Overall survival

Incidence of adverse events

Changes from baseline in laboratory tests for immunological safety

Full Information

NCT ID

NCT02293707

First Posted

November 14, 2014

Last Updated

July 21, 2020

Sponsor

Laboratoires Leurquin Mediolanum

Collaborators

Universita degli Studi di Genova

1. Study Identification

Unique Protocol Identification Number

NCT02293707

Brief Title

A Phase II Randomised Trial of Three Regimens of GX301 Vaccination in Castration-resistant Prostate Cancer

Official Title

A Randomised, Parallel-group, Open-label Phase II Trial of the Immunological Effects of Three Regimens of GX301 Vaccination in Castration-resistant Prostate Cancer Patients Who Have Achieved Response or Disease Stability With First-line Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

November 2014 (undefined)

Primary Completion Date

August 2018 (Actual)

Study Completion Date

November 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Laboratoires Leurquin Mediolanum

Collaborators

Universita degli Studi di Genova

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

GX301 is an experimental therapeutic vaccine directed against human telomerase, an enzyme playing an essential role in cancer cell proliferation. This clinical trial will test three different GX301 administration regimens in castration-resistant prostate cancer patients who have achieved response or disease stability with first-line docetaxel treatment. This is aimed at identifying an optimal vaccination regimen. The three regimens will primarily be compared for their efficacy and safety in inducing vaccine-specific immunological responses over a period of 6 months following treatment initiation. In addition, patients will be observed for the occurrence of disease progression and for their vital status up to 24 months.

Detailed Description

GX301, an experimental therapeutic (anti-cancer) vaccine, is composed of four immunogenic peptides from human telomerase and two complementary adjuvants, Montanide ISA-51 VG and imiquimod. An earlier Phase 1 study of GX301 has provided evidence of vaccine-specific immune response in a small sample of stage 4 prostate cancer patients given eight GX301 administrations over 9 weeks. The present Phase 2, randomised, parallel-group, multicentre trial is aimed at comparing three different GX301 administration regimens in patients with progressive, castration-resistant prostate cancer who have completed a first-line docetaxel treatment and have achieved response to chemotherapy or disease stability. Primary comparisons will include regimen efficacy in inducing vaccine-specific immunological responses over a period of 6 months following randomisation; and treatment safety and tolerability over the same period. A further study aim is to investigate whether achievement of immunological response, irrespective of the assigned GX301 regimen, is related to progression-free and/or overall survival. Eligible patients will be randomly assigned to receive one of three GX301 vaccination regimens consisting of two, four or eight administrations, respectively, each regimen being given over a fixed 9-week period. Randomisation ratio will be 1:1:1. Randomisation will be stratified by previous cumulative exposure to docetaxel. Following randomisation, immunological responses to GX301 will be determined over a 6-month period. However, on-study patient observation will be continued until the occurrence of one of the following end-points, whichever the earliest: (a) disease progression; (b) death; (c) completion of an 18-month observation period; or (d) patient's decision to terminate his participation in the study. All patients discharged from the trial for reasons (a) or (c) will undergo a follow-up to ascertain survival until 24 months from randomisation. Data analysis will be carried out in two sequential steps. The first step will focus on co-primary outcomes and will therefore take place upon completion of the study dataset up to the 6-month time-point. The second step will incorporate secondary outcomes and will therefore be conducted upon completion of the full study dataset.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

Castration-resistant prostate cancer, Therapeutic vaccine, Telomerase vaccine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

99 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GX301 Regimen A (8 administrations)

Arm Type

Experimental

Arm Description

Administration time frame: Day 1 to Day 63.

Arm Title

GX301 Regimen B (4 administrations)

Arm Type

Experimental

Arm Description

Administration time frame: Day 1 to Day 63.

Arm Title

GX301 Regimen C (2 administrations)

Arm Type

Experimental

Arm Description

Administration time frame: Day 1 to Day 63.

Intervention Type

Biological

Intervention Name(s)

GX301

Intervention Description

GX301 therapy consists of four human telomerase reverse transcriptase (hTERT) peptides and two adjuvants. Peptides are hTERT (540-548) Acetate, hTERT (611-626) Acetate, hTERT (672-686) Acetate and hTERT (766-780) Acetate. Adjuvants are Montanide ISA 51 VG and imiquimod 5% cream (Aldara). Each GX301 administration will consist of four intradermal injections - one injection for each hTERT peptide - given at the same time and followed by topical application of imiquimod. Each intradermal injection will consist of a fixed hTERT peptide dose, 500 µg, reconstituted as a solution and mixed with Montanide ISA 51 VG.

Primary Outcome Measure Information:

Title

Achievement of immunological response

Time Frame

Days 90 and 180 following randomisation

Title

Incidence of adverse events

Time Frame

Up to Day 180

Title

Changes from baseline in laboratory tests for immunological safety

Time Frame

Days 63, 90 and 180

Secondary Outcome Measure Information:

Title

Changes from baseline in serum prostate-specific antigen (PSA)

Time Frame

Up to Day 540 or end of observation (if earlier)

Title

Progression-free survival

Time Frame

Up to Day 540 or end of observation (if earlier)

Title

Overall survival

Time Frame

Up to Day 720

Title

Incidence of adverse events

Time Frame

Up to Day 540 or end of observation (if earlier)

Title

Changes from baseline in laboratory tests for immunological safety

Time Frame

Up to Day 540 or end of observation (if earlier)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Documented patient history Histologically confirmed diagnosis of prostate cancer, with an available Gleason score. Diagnosis of progressive, castration-resistant prostate cancer (CRPC), leading to inception of first-line chemotherapy with a docetaxel-based regimen. Completion of chemotherapy with a cumulative delivered dose of 300 to 825 mg/m2 docetaxel. Note: Pre-chemotherapy exposure to abiraterone and prednisone does not preclude eligibility, provided that both agents have been discontinued prior to initiation of docetaxel. Current patient status Ability to understand study-related patient information and provision of written informed consent for participation in the study. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least 6 months. An interval ≥4 weeks elapsed from the last docetaxel administration. Documented achievement of response or disease stability with docetaxel chemotherapy. Absence of cancer-related symptoms suggesting clinical disease progression. Current castrate testosterone level (≤50 ng/dL) due to current gonadotropin-releasing hormone (GnRH) agonist or antagonist therapy or past orchiectomy. Haematology and blood chemistry tests within specified limits. Successful recovery from acute toxicities from prior chemotherapy. Confirmation from the immunology laboratory that the blood sample provided for baseline immunological tests is technically adequate. Exclusion Criteria: Known intolerance to Montanide or imiquimod. Known presence of brain metastatic disease or spinal cord compression. Radiotherapy within the past 4 weeks. Concomitant presence of other primary malignancy Major surgery within 4 weeks prior to randomisation. Cardiovascular illness or complication which, in Investigator's judgment, compromises prognosis at 6 months or prevents the patient from following study procedures. Serious uncontrolled infection. Known presence of active autoimmune disease. Known presence of acquired, hereditary, or congenital immunodeficiency. HIV infection. Current need for immunosuppressive drug therapy, including systemic corticosteroids. Current need for denosumab therapy. (Patients under bisphosphonate treatment are eligible). Skin disease interfering with evaluation of local tolerance of GX301 injections. Participation in any interventional drug or medical device study within 30 days prior to treatment start.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Francesco Boccardo, MD

Organizational Affiliation

DIMI, Università di Genova - Clinica di Oncologia Medica, IRCCS San Martino-IST

Official's Role

Principal Investigator

Facility Information:

Facility Name

S.C. di Oncologia, A.S.O. "Santi Antonio e Biagio e Cesare Arrigo"

City

Alessandria

ZIP/Postal Code

15121

Country

Italy

Facility Name

Oncologia Medica A, Centro di Riferimento Oncologico (CRO)

City

Aviano

ZIP/Postal Code

33081

Country

Italy

Facility Name

Oncologia Medica, Azienda Ospedaliero Universitaria - Policlinico Consorziale

City

Bari

ZIP/Postal Code

70124

Country

Italy

Facility Name

U.O.C. Urologia 1, A.O.U. Consorziale Policlinico di Bari

City

Bari

ZIP/Postal Code

70124

Country

Italy

Facility Name

Oncologia Medica, A.O. Spedali Civili

City

Brescia

ZIP/Postal Code

25123

Country

Italy

Facility Name

S.C. Oncologia Medica, Presidio Ospedaliero Busto Arsizio

City

Busto Arsizio

ZIP/Postal Code

21052

Country

Italy

Facility Name

IRCCS Fondazione del Piemonte per l'Oncologia (FPO)

City

Candiolo

ZIP/Postal Code

10060

Country

Italy

Facility Name

Clinica di Oncologia Medica, IRCCS San Martino-IST

City

Genova

ZIP/Postal Code

16132

Country

Italy

Facility Name

U.O. Medicina Oncologica - Ospedale San Raffaele IRCCS

City

Milano

ZIP/Postal Code

20132

Country

Italy

Facility Name

Unità Oncologica Medica Urogenitale, Istituto Europeo di Oncologia

City

Milano

ZIP/Postal Code

20141

Country

Italy

Facility Name

Dipartimento Uro-Ginecologico, IRCCS Istituto Nazionale Tumori - Fondazione Pascale

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Facility Name

U.O.C. di Oncologia Medica, A.O.R.N. "Antonio Cardarelli"

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Facility Name

Oncologia Medica, A.O. Universitaria San Luigi Gonzaga

City

Orbassano

ZIP/Postal Code

10043

Country

Italy

Facility Name

U.O. di Oncologia, AUSL di Piacenza

City

Piacenza

ZIP/Postal Code

29100

Country

Italy

Facility Name

Unita Oncologica, Azienda Ospedaliera S. Maria degli Angeli

City

Pordenone

ZIP/Postal Code

33170

Country

Italy

Facility Name

U.O.C. di Oncologia Medica, Policlinico "Le Scotte"

City

Siena

ZIP/Postal Code

53100

Country

Italy

Facility Name

Oncologia Medica d.U., Policlinico G.B. Rossi, A.O.U.I. Verona

City

Verona

ZIP/Postal Code

37134

Country

Italy

Facility Name

Medical Oncology, Hospital Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Clìnic i Provincial de Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Medical Oncology, Institut Català d'Oncologìa

City

L'Hospitalet De Llobregat, Barcelona

ZIP/Postal Code

08907

Country

Spain

Facility Name

Oncología, Hospital Universitario Gregorio Marañón

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Servicio de Oncologìa Médica, Hospital Universitario Ramòn y Cajal

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Oncología Médica, Hospital Clínico San Carlos

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Oncology, Corporaciò Sanitària Parc Taulì

City

Sabadell, Barcelona

ZIP/Postal Code

08208

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

23591981

Citation

Fenoglio D, Traverso P, Parodi A, Tomasello L, Negrini S, Kalli F, Battaglia F, Ferrera F, Sciallero S, Murdaca G, Setti M, Sobrero A, Boccardo F, Cittadini G, Puppo F, Criscuolo D, Carmignani G, Indiveri F, Filaci G. A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer. Cancer Immunol Immunother. 2013 Jun;62(6):1041-52. doi: 10.1007/s00262-013-1415-9. Epub 2013 Apr 17.

Results Reference

background

PubMed Identifier

25714118

Citation

Fenoglio D, Parodi A, Lavieri R, Kalli F, Ferrera F, Tagliamacco A, Guastalla A, Lamperti MG, Giacomini M, Filaci G. Immunogenicity of GX301 cancer vaccine: Four (telomerase peptides) are better than one. Hum Vaccin Immunother. 2015;11(4):838-50. doi: 10.1080/21645515.2015.1012032.

Results Reference

background

PubMed Identifier

34351436

Citation

Filaci G, Fenoglio D, Nole F, Zanardi E, Tomasello L, Aglietta M, Del Conte G, Carles J, Morales-Barrera R, Guglielmini P, Scagliotti G, Signori A, Parodi A, Kalli F, Astone G, Ferrera F, Altosole T, Lamperti G, Criscuolo D, Gianese F, Boccardo F. Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial. Cancer Immunol Immunother. 2021 Dec;70(12):3679-3692. doi: 10.1007/s00262-021-03024-0. Epub 2021 Aug 5.

Results Reference

derived

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A Phase II Randomised Trial of Three Regimens of GX301 Vaccination in Castration-resistant Prostate Cancer

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