Cisplatin-based Chemotherapy Combined With P16_37-63 Peptide Vaccination in Patients With HPV-positive Cancers

NCT02526316 | Completed Phase 1 DMC

• 1 other identifier: VICORYX-2
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

HPV-induced Cancers

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Immune response against peptide P16_37-63

  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

  week 1

• Immune response against peptide P16_37-63

  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

  week 3

• Immune response against peptide P16_37-63

  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

  week 9

• Immune response against peptide P16_37-63

  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

  week 11

• Immune response against peptide P16_37-63

  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

  week 17

• Immune response against peptide P16_37-63

  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

  week 19

• Immune response against peptide P16_37-63

  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

  week 25

Secondary Outcomes (4)

• Tumor response as assessed by CT or MRI scans according to RECIST

  baseline, after every cycle up to 25 weeks

• Case wise listing of progression-free survival

  four weeks after last vaccination

• Safety of the vaccine administration as assessed by the number and severity of adverse events categorized according to CTC criteria version 4.0.

  up tp week 25, 4 weeks after last vaccination

• Case wise listing of overall survival

  four weeks after last vaccination

Study Arms (1)

P16_37-63 Vaccination

OTHER

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; Biological: P16_37-63 peptide without Montanide® ISA-51 VG

Interventions

P16_37-63 peptide combined with Montanide® ISA-51 VG BIOLOGICAL

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

P16_37-63 Vaccination

P16_37-63 peptide without Montanide® ISA-51 VG BIOLOGICAL

Patients will receive 30 mcg P16\_37-63 peptide injected intradermally for test on delayed-type hypersensitivity (DTH) reactions.

P16_37-63 Vaccination

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Oryx GmbH & Co. KG: lead

Study Sites (1)

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Penile Neoplasms; Anus Neoplasms; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Vulvar Diseases; Vaginal Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Penile Diseases; Male Urogenital Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2015
• First Posted: August 18, 2015
• Study Start: June 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: July 2, 2017

Record last verified: 2017-06

Locations

DE (1)