E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced HPV- and p16INK4a-positive cervical, vulvar, vaginal, penile, anal or head and neck cancer |
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E.1.1.1 | Medical condition in easily understood language |
advanced cervical, vulvar, vaginal, penile, anal or head and neck cancer that is tested HPV- and p16INK4a-positive |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10008230 |
E.1.2 | Term | Cervix neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10002125 |
E.1.2 | Term | Anal canal neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026339 |
E.1.2 | Term | Malignant neoplasm of penis, part unspecified |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10046896 |
E.1.2 | Term | Vaginal neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10047750 |
E.1.2 | Term | Vulval neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase I Part:
Safety of the vaccine
Phase IIa Part:
Immune response against the p16_37-63 peptide |
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E.2.2 | Secondary objectives of the trial |
Phase I Part:
Immune response against the p16_37-63 peptide
Tumor response
Phase IIa Part:
Safety of the vaccine
Tumor response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Histologically confirmed, advanced HPV-positive cancers of entities and stages as defined in the following listing under progression, regression or with stable disease (and still incurable) after standard therapy or after refusal of standard therapy as defined in the following listing or with contraindications for standard treatment
•HPV positivity
•Diffuse expression of p16INK4a in the tumor
•Expected survival of at least six months.
•Full recovery from surgery, chemo therapy or radiation therapy.
•ECOG performance status 0, 1 or 2.
•adequate blood and biochemistry parameters
•Male or female* patients ≥ 18 years old
•Patient´s written informed consent for participation in the trial
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E.4 | Principal exclusion criteria |
•Prior treatment with P16_37-63 peptide
•Clinically significant heart disease (NYHA Class III or IV).
•Other serious illnesses, eg, serious infections requiring antibiotics or bleeding disorders.
•History of immunodeficiency disease or autoimmune disease.
•Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available.
•HBV, HCV or HIV positivity.
•Chemotherapy, any type of radiation therapy, or immunotherapy within 4 weeks before study entry
•Concomitant treatment with steroids, antihistaminic drugs, or nonsteroidal anti-inflammatory drugs (unless used in low doses for prevention of an acute cardiovascular event or for pain control). Topical or inhalational steroids are permitted.
•Participation in any other clinical trial involving another investigational agent within 4 weeks.
•Pregnancy or lactation.
•Women of childbearing potential who are not using a medically acceptable means of contraception.
•Psychiatric or addictive disorders that may compromise the ability to give informed consent.
•Lack of availability of a patient for immunological and clinical follow-up assessment.
•Brain metastases (symptomatic and non-symptomatic) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase IIa: Immune response against peptide P16_37-63. A positive immune response is defined as positive DTH response against peptide P16_37-63 or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) and/or CD8 and/or CD4 cellular (IFN gamma ELISpot for the detection of p16INK4a-specific T cells) immune response exceeding the assay specific cut-off values for a positive response against peptide P16_37-63. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
humoral immune response at weeks 1, 3, 9, 11, 17, 19, 25
cellular immune response and DTH: weeks 1, 9, 17, 25. |
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E.5.2 | Secondary end point(s) |
Safety of the vaccine
Tumor response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
safety: at every visit
tumor response: every 8 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit is the end of the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |