Patients with advanced (Stage IIIb-IVa with involvement of lymph nodes beyond the renal vein) or metastatic (stage IVb )or recurrent HPV16 positive cervical cancer for whom no curative treatment options exist MedDRA version: 18.0 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Human Papilloma Virus (HPV) type 16 E6/E7 synthetic long peptide (SLP®) vaccine
Product Code: ISA101
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed
Sponsors
ISA Therapeutics B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Women = 18 years of age. 2) Cervical cancer confirmed by histology. 3) Advanced (Stage IIIb/IVa with para-aortic lymph nodes involvement beyond the renal vein) or, metastatic (Stage IVb ) or recurrent cervical cancer confirmed by clinical and/or radiological proof with no curative treatment options. 4) Tumour must be HPV16 positive (to be determined on archival tumour tissue (=10 years old); if that is not available a pre-treatment biopsy will be required). 5) Patients should be eligible for chemotherapy with carboplatin and paclitaxel. 6) Performance status (WHO scale/ECOG) = 1. 7) Written informed consent according to local guidelines. 8) Written approval by the treating physician / investigator of his/her clinical judgement that the patient has a reasonable life expectancy and is sufficiently fit and motivated to complete the study treatment and comply to all study procedures specified by the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 43 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Treatment: 1) Prior treatment with anti-HPV agents. 2) Chronic systemic steroid use. Local application (i.e. stable doses of topical or inhaled corticosteroids) is allowed. 3) Less than 4 weeks since the last treatment with other cancer therapies, (i.e. endocrine therapy, immunotherapy, radiotherapy, chemotherapy, etc), less than 8 weeks for cranial radiotherapy, and less than 6 weeks for nitrosoureas and mitomycin C. 4) Toxicities resulting from previous anti-cancer therapy (radiation, chemotherapy or surgery) must be resolved to = grade 2 as defined by CTCAE version 4.0. 5) Recent treatment (within 30 days of first study treatment) with another investigational drug. Haematology and biochemistry: 6) Inadequate bone marrow function: Absolute Neutrophil Count (ANC) 2 x upper normal limit (ULN); or • ASAT or ALAT > 2.5 x ULN (> 5 x ULN in patients with liver metastases); or • Alkaline phosphatase levels > 2.5 x ULN (> 5 x ULN in patients with liver metastases, or > 10 x ULN in patients with bone metastases). Other: 8) Clinical suspicion or radiological evidence of brain or leptomeningeal metastases. A CT/MRI scan should be performed if there is any clinical evidence of brain metastases. 9) Previous or current malignancies at other sites, with the exception of basal or squamous cell carcinoma of the skin and with the exception of other malignancies from which the patient may be considered cured as evidenced by complete regression of all lesions >10 years ago. 10) Active HIV, chronic hepatitis B or C infection. 11) Patients of childbearing potential (defined as 180 mm Hg and/or diastolic > 110mm Hg). 15) Clinically significant (i.e. active) cardiovascular disease defined as: • Stroke within = 6 months prior to day 1; • Transient Ischemic Attack (TIA) within = 6 months prior to day 1; • Myocardial infarction within = 6 months prior to day 1; • Unstable angina; • New York Heart Association (NYHA) Grade II or greater Congestive Heart Failure (CHF); • Serious cardiac arrhythmia requiring medication; 16) History of severe bronchial asthma and/or severe allergy. 17) Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, auto-immune diseases) that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and HPV-specific immune responses of the therapeutic Human Papilloma Virus Type 16 (HPV16) E6/E7 Synthetic Long Peptides Vaccine (ISA101) at different doses with or without interferon alpha as combination therapy with carboplatin and paclitaxel in women with HPV16 positive advanced or recurrent cervical cancer who have no curative treatment options;Secondary Objective: To evaluate the clinical efficacy of the therapeutic Human Papilloma Virus Type 16 (HPV16) E6/E7 Synthetic Long Peptides Vaccine (ISA101) at different doses with or without interferon alpha as combination therapy with carboplatin and paclitaxel in women with HPV16 positive advanced or recurrent cervical ;Primary end point(s): Safety will be determined by the incidence rate at each dose level based on the following safety parameters: adverse events (AE) and serious adverse events (SAEs), changes in haematology and chemistry values, including those associated with hepatic and renal function, and assessment of physical examinations, vital signs and performance status. NCI-CTCAE version 4.0 will be used. HPV-specific immune responses: HPV-specific immune responses to the ISA101 vaccine with or without pegylated IFNa in combination with carboplatin and paclitaxel will be determined by the quality, breadth and magnitude of the HPV16 E6/E7-specific T-cell responses as measured by a validated assay (IFN?-ELISPOT) following injection of the different doses of the ISA101 vaccine. ;Timepoint(s) of evaluation of this end point: during 18 weeks of duration of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Antitumor efficacy according to RECIST 1.1: o Objective Response Rate (ORR) will be calculated as the proportion of patients with a best overall response of confirmed Complete Response (CR) or Partial Response (PR). o Disease Control Rate (DCR) will be calculated as the proportion of patients with a best overall response of confirmed CR, PR or Stable Disease (SD). o Progression Free Survival (PFS) is defined as the time from start of carboplatin and paclitaxel treatment to the documented progression or death from any cause ;Timepoint(s) of evaluation of this end point: At 9 weeks, 18 weeks, and a follow up at 30 weeks, 42 weeks and 52 weeks excluding patients with confirmation of progressive disease | — |
Countries
Belgium, Germany, Netherlands
Contacts
Public ContactClinial Department
ISA Therapeutics B.V.
Outcome results
None listed