An experimental study in women with cervical cancer to test the safety and activation of the patient's own immune system after treatment with chemotherapy in combination with a vaccine directed against an infection with Human Papilloma Virus Type 16 (HPV16).
- Conditions
- 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 existMedDRA version: 19.0 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001804-12-BE
- Lead Sponsor
- ISA Therapeutics B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 90
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) For cohort 10 (and 12), patients should be eligible to receive bevacizumab at each site per standard of care, patients may be primary stage IVB (including persistent) or first recurrent carcinoma of the uterine cervix (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma). Prior treatment with chemotherapy for recurrent disease is not allowed. However, one prior line of chemotherapy with platinum during primary radio-chemotherapy or platinum-base chemotherapy as neoadjuvant chemotherapy prior to surgery is permitted.
5) 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).
6) Patients should be eligible for chemotherapy with carboplatin and paclitaxel.
7) Performance status (WHO scale/ECOG) = 1.
8) Written informed consent according to local guidelines.
9) 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 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
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.
6) Patients with known hypersensitivity to any component of the Investigational Medicinal Product (e.g. ISA101/ISA101b, Montanide, dimethylsulfoxide, Macrogolglycerol Ricinoleate, also known as cremophore, or pegylated IFNa for those subjects assigned to pegylated IFNa cohorts).
Haematology and biochemistry:
7) Inadequate bone marrow function: Absolute Neutrophil Count (ANC) < 1.5 x 109/L, or platelet count < 100 x 109/L or hemoglobin < 6 mmol/L.
8) Inadequate liver function, defined as:
• Serum (total) bilirubin > 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:
9) 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.
10) 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.
11) Active HIV, chronic hepatitis B or C infection.
12) Patients of childbearing potential (defined as < 2 years after last menstruation and having an intact reproductive system), not willing to consistently and correctly use a contraceptive method according to ICH (M3) resulting in low failure rate, i.e. less than 1% per year such as oral contraceptives or use of effective means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel).
13) Pregnancy or lactation. Serum pregnancy test to be performed within 7 days prior to study treatment start in patients of childbearing potential.
14) Major surgical procedure within 28 days prior to the first study treatment.
15) Uncontrolled sustained hypertension (systolic > 180 mm Hg and/or diastolic > 110mm Hg).
16) 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 Hea
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method