Cisplatin-based Chemotherapy Combined With P16_37-63 Peptide Vaccination in Patients With HPV-positive Cancers (VICORYX-2)

Study Description

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Brief Summary:

The study will include 10 patients with HPV-associated ano-genital cancer (cervical, vulvar, vaginal, penile, anal) or HPV-associated head and neck cancer, who are planned to receive a cisplatin-based chemotherapy (alternatively a carboplatin-based chemotherapy may be selected by investigators choice). Patients will receive P16_37-63 peptide (100 µg) combined with Montanide® ISA-51 VG subcutaneously once a week for four weeks, followed by a 4 week rest period (1 cycle). The vaccination is to be started one week before the initiation or continuation of the cisplatin-based chemotherapy. Concurrent radiation is allowed and should be documented. The vaccination schedule will be repeated up to a total of 3 cycles (= 6 months) or until progression or intolerable toxicity. If chemotherapy is withheld (e.g. for toxicity), vaccination treatment can be continued.

Condition or disease	Intervention/treatment	Phase
HPV-induced Cancers	Biological: P16_37-63 peptide combined with Montanide® ISA-51 VG; Biological: P16_37-63 peptide without Montanide® ISA-51 VG	Phase 1

Detailed Description:

10 patients with HPV- and p16INK4a-positive cervical, vulvar, vaginal, penile, anal or head and neck cancer will be enrolled. The p16INK4a-peptide (p16INK4a-37-63, 100 mcg) mixed with MONTANIDE ISA-51 VG (0.3 ml) will be administered subcutaneously once weekly for four weeks, followed by a 4-week rest period (1 cycle). This schedule will be repeated for a total of 3 cycles (= 6 months) or until tumor progression or intolerable toxicity is documented. The first application will be done one week before chemotherapy initiation or continuation. Concurrent radiation is allowed and should be documented. If chemotherapy is withhold for toxicity, vaccination treatment can be continued.

Patients will be seen at baseline/screening and at every visit for safety assessment until disease progression or discontinuation of trial therapy for other reasons. Immunological assessments will be made in all patients. The immunological assessment includes the delayed time hypersensitivity response (DTH) against the P16_37-63 peptide. Therefore in week 1, 9, 17 and 25, 30 mcg P16_37-63 peptide solution without MONTANIDE ISA-51 VG will be injected at a separate site from the vaccination site intradermally. Immunological responses are evaluated at baseline and after vaccination in weeks 9, 17 and 25 (ELISPOT) and in weeks 1, 3, 9, 11, 17, 19 and 25 (ELISA) and are compared to the antigen-specific immune response measured before vaccination (week 1). Radiological tumor assessment (CT, MRI) will be performed at baseline and then every 8 weeks (after every cycle). There will be a follow- up visit four weeks after the last vaccination for safety. Further follow-up regarding progression and death can be performed, e.g. via a phone call. Autoimmunity will be assessed every 8 weeks. Safety of the immunization will be analyzed as assessed by the number and severity of adverse events categorized according to CTC criteria

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	11 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Pilot Study on Concurrent Cisplatin-based Chemotherapy Combined With Vaccination Therapy With the P16_37-63 Peptide in Patients With HPV- and p16INK4a-positive Cancer
Study Start Date :	June 2015
Actual Primary Completion Date :	May 2017
Actual Study Completion Date :	May 2017

Arms and Interventions

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Arm

Intervention/treatment

P16_37-63 Vaccination; Patients will receive P16_37-63 peptide (100 μg) combined with Montanide® ISA-51 VG subcutaneously once a week for four weeks, followed by a 4 week rest period (1 cycle). The vaccination is to be started one week before the initiation or continuation of the cisplatin-based chemotherapy.

Biological: P16_37-63 peptide combined with Montanide® ISA-51 VG; Patients will receive P16_37-63 peptide (100 µg) combined with Montanide® ISA-51 VG vaccination subcutaneously once a week for four weeks, followed by a 4 week rest period Biological: P16_37-63 peptide without Montanide® ISA-51 VG; Patients will receive 30 mcg P16_37-63 peptide injected intradermally for test on delayed-type hypersensitivity (DTH) reactions.

Outcome Measures

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Primary Outcome Measures :

1. Immune response against peptide P16_37-63 [ Time Frame: week 1 ]
   A positive immune response is defined as positive DTH response against peptide P16_37-63 and/or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) 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
2. Immune response against peptide P16_37-63 [ Time Frame: week 3 ]
   A positive immune response is defined as positive DTH response against peptide P16_37-63 and/or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) 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
3. Immune response against peptide P16_37-63 [ Time Frame: week 9 ]
   A positive immune response is defined as positive DTH response against peptide P16_37-63 and/or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) 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
4. Immune response against peptide P16_37-63 [ Time Frame: week 11 ]
   A positive immune response is defined as positive DTH response against peptide P16_37-63 and/or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) 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
5. Immune response against peptide P16_37-63 [ Time Frame: week 17 ]
   A positive immune response is defined as positive DTH response against peptide P16_37-63 and/or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) 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
6. Immune response against peptide P16_37-63 [ Time Frame: week 19 ]
   A positive immune response is defined as positive DTH response against peptide P16_37-63 and/or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) 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
7. Immune response against peptide P16_37-63 [ Time Frame: week 25 ]
   A positive immune response is defined as positive DTH response against peptide P16_37-63 and/or a humoral (ELISA for the detection of p16-specific IgG/IgM/IgA) 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

Secondary Outcome Measures :

1. Tumor response as assessed by CT or MRI scans according to RECIST [ Time Frame: baseline, after every cycle up to 25 weeks ]
2. Case wise listing of progression-free survival [ Time Frame: four weeks after last vaccination ]
3. Safety of the vaccine administration as assessed by the number and severity of adverse events categorized according to CTC criteria version 4.0. [ Time Frame: up tp week 25, 4 weeks after last vaccination ]
4. Case wise listing of overall survival [ Time Frame: four weeks after last vaccination ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Histologically confirmed, advanced HPV-positive cervical, vulvar, vaginal, penile, anal or head and neck cancer cancer
• HPV positivity as tested by HPV genotyping from paraffin embedded tumor tissue using Linear Array HPV Genotyping test from Roche Diagnostics Germany GmbH
• Diffuse expression of p16INK4a in the tumor as analyzed by immunohistochemistry on paraffin embedded tumor tissue using the CINtec p16INK4a histology kit
• Planned cisplatin-based chemotherapy with an expected duration of at least 2 months. A carboplatin-based therapy may be selected as an alternative by investigators choice
• Expected survival of at least 3 months
• Full recovery from prior surgery, chemotherapy or radiation therapy (except for alopecia, fatigue or neurotoxicity of grade 1 or 2
• ECOG performance status 0, 1 or 2
• The following laboratory results: Neutrophil count ≥ 1.5 x 109/L Lymphocyte count ≥ 0.5 x 109/L Platelet count ≥ 100 x 109/L Serum bilirubin < 2mg/dL
• Patient´s written informed consent for participation in the trial

Exclusion Criteria:

• Prior treatment with P16_37-63 peptide
• Clinically significant heart disease (NYHA Class III or IV)
• Other serious illnesses, e.g., 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
• Known HBV, HCV or HIV positivity
• 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. Appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)
• 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)

Contacts and Locations

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Locations

Germany
Krankenhaus Nordwest
Frankfurt, Germany, 60488

Sponsors and Collaborators

Oryx GmbH & Co. KG

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Oryx GmbH & Co. KG
ClinicalTrials.gov Identifier:	NCT02526316 History of Changes
Other Study ID Numbers:	VICORYX-2
First Posted:	August 18, 2015
Last Update Posted:	July 2, 2017
Last Verified:	June 2017

Keywords provided by Oryx GmbH & Co. KG:

cervical cancer; vulvar cancer; vaginal cancer	penile cancer; anal cancer; head and neck cancer

Additional relevant MeSH terms:

Cisplatin; Vaccines; Freund's Adjuvant; Antineoplastic Agents	Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic