Trial of RNActive®-Derived Prostate Cancer Vaccine in Metastatic Castrate-refractory Prostate Cancer

Phase 1

Terminated

• Conditions: Prostate Cancer

• Registration Number: NCT01817738
• Lead Sponsor: CureVac

Brief Summary

The purpose of this study is to determine whether the new RNActive®-derived prostate cancer vaccine CV9104 prolongs survival in patients with asymptomatic or minimally symptomatic metastatic prostate cancer that is castrate resistant.

Detailed Description

The study is the first clinical study with the new prostate cancer vaccine CV9104. This vaccine is composed of 6RNActive®-based compounds, each encoding for an antigen that is overexpressed in prostate cancer compared to healthy tissues. RNActive®-based vaccines are a novel class of vaccines based on messenger RNA.

The study is a double-blind randomized placebo-controlled phase I/II trial in men with asymptomatic- minimally symptomatic metastatic castrate-refractory prostate cancer.

The phase 1 (safety lead- in) part of the trial has the primary objective to assess the safety of CV9104 and to determine the dose for the randomized phase II part.

The primary objective of the phase II part is to compare overall survival in patients treated with CV9104 compared to patients treated with placebo.

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2013-02-08
• Study First Submitted QC: 2013-03-22
• Study First Posted: 2013-03-25
• Status Verified: 2016-04
• Primary Completion: 2016-08
• Study Completion: 2017-01
• Last Update Submitted: 2017-02-15
• Last Update Posted: 2017-02-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 197

Inclusion Criteria

1. Male, age ≥18 years

2. Histologically confirmed castrate refractory metastatic adenocarcinoma of the prostate with progressive disease after surgical castration or during androgen suppression therapy including a GNRH agonist or antagonist and after at least 1 additional anti-hormonal manipulation; and serum testosterone level of < 50 ng/dL or < 1.7 nmol/L

   Progression will be confirmed either

   • radiologically or
   • by 2 consecutive rises of PSA, measured at least 1 week apart, resulting at least in a 50% increase over the nadir and a PSA > 2 ng/mL.
   • An antiandrogen withdrawal response must have been excluded after discontinuation of antiandrogen therapy for at least 6 weeks.

3. Metastatic disease confirmed by imaging

4. ECOG performance status 0 or 1

Key

Exclusion Criteria

1. Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
2. Treatment with any investigational anticancer agents within 4 weeks prior to first dose of study drug
3. Systemic treatment with immunosuppressive agents
4. Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection (upper arms or thighs) preventing the administration of i.d. injections into areas of healthy skin.
5. History of or current autoimmune disorders
6. Primary or secondary immune deficiency.
7. Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
8. Symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris or myocardial infarction, significant cardiac arrhythmia, history of stroke or transient ischemic attack, all within 6 months prior to enrolment or severe hypertension according to WHO criteria or uncontrolled hypertension at the time of enrolment (systolic blood pressure ≥ 180 mm Hg)´
9. Previous chemotherapy for metastatic PCA.
10. Previous anti-hormonal treatment with abiraterone or any other investigational anti-hormonal treatment.
11. Cancer-related pain requiring opioid narcotics within 28 days before enrolment or an average pain score of > 3 on a visual analogue scale.
12. Presence of visceral metastases.
13. History of other malignancies other than PCA over the last 5 years (except basal cell carcinoma of the skin).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Phase I (Safety Lead-In): Occurrence of dose-limiting toxicity (DLT) during the first 4 weeks of treatment (after administration of 3 vaccinations and after a 1 week observation period	Up to 4 weeks	Safety Lead in Portion: Patients will receive CV9104 at a starting dose of 1920 µg in weeks 1, 2 and 3. Safety lead-in patients will be observed for DLTs until 1 week after Vaccination 3 (week 4). In case no DLTs will be observed vaccinations will continue in weeks 5, 7, 9, 12, 15, 18 and 24, then every 6 weeks for up to 12 months after the first vaccination and then every 3 months thereafter until one of the criteria for study treatment discontinuation is met
Phase II (Randomised Portion): Overall Survival from time of randomisation- up to 3.5-4 years.	Overall survival will be assessed during the lifetime of the study

Secondary Outcome Measures

Name	Time	Method
Progression free survival from date of randomisation	Every 3 months for up to 2 years
Cellular and humoral immune response rate against the 6 antigens encoded by CV9104	Immune responses will be assessed at baseline, in week 6 and week 24 after start of vaccination
Progression free survival from randomisation until second progression on first subsequent therapy	Every 3 and 6 months up to 2 years
Absolute change and area under the curve from baseline EQ-5D score and pain sub-score	Assessments at baseline, weeks 5, 9,18, 24 and thereafter every 3 months for up to 2 years
Progression free survival from start of first subsequent systemic therapy	Every 6 months until 2 years
Percent change to maximal and to minimal PSA from baseline and before start of first subsequent systemic cancer therapy and from start of first systemic therapy to end of first subsequent systemic therapy	Every 3 months up to 2 years
Time to symptom progression based on FACT P score and subscores	Assessments at baseline, weeks 5, 9,18, 24 and every 3 months for up to 2 years

Trial Locations

Locations (48)

Krajská zdravotní, a.s. - Nemocnice Chomutov, o.z.Onkologické oddělení; 🇨🇿 Chomutov, Czech Republic

Fakultní nemocnice Olomouc, Urologická klinika; 🇨🇿 Olomouc, Czech Republic

Multiscan, a.s, Oddělení klinické a radiační onkologie; 🇨🇿 Pardubice, Czech Republic

Thomayerova nemocnice, Urologické oddělení; 🇨🇿 Praha, Czech Republic

Krajská zdravotní, a.s. - Masarykova nemocnice Ústí nad Labem; 🇨🇿 Usti nad Labem, Czech Republic

Institut Gustave Roussy; 🇫🇷 Villejuif cedex, France

Universitätsklinikum Aachen Klinik für Urologie; 🇩🇪 Aachen, Germany

Vivantes Klinikum Am Urban Klinik für Urologie; 🇩🇪 Berlin, Germany

Medizinisches Zentrum Friedensplatz; 🇩🇪 Bonn, Germany

Universitätsklinikum Dresden Klinik und Poliklinik für Urologie; 🇩🇪 Dresden, Germany

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