A multicenter, open label Phase I/II study to determine the safety and immune modulating effects of the therapeutic Human Papilloma Virus Type 16 (HPV16) E6/E7 Synthetic Long Peptides Vaccine (ISA101/ISA101b) immunotherapy in combination with standard of care therapy (carboplatin and paclitaxel with or without bevacizumab) in women with HPV16 positive advanced or recurrent cervical cancer who have no curative treatment options.
- Conditions
- advanced or recurrent cervical cancercervical cancer10038594
- Registration Number
- NL-OMON45132
- Lead Sponsor
- ISA Therapeutics B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 50
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 permitted. 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, and have consented with chemotherapy with carboplatin and paclitaxel, before the start of the informed consent procedure for the study.
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 judgment 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.
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 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
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 pegylated, cremophor also known as Macrogolglycerol Ricinoleate, or IFNa for those subjects assigned to pegylated IFNa cohorts).
7) Any contraindication to the use of authorized applied products (i.e. paclitaxel, carboplatin or bevacizumab).
8) Inadequate bone marrow function
9) Inadequate liver function
10) Clinical suspicion or radiological evidence of brain or leptomeningeal metastases.
11) Previous or current malignancies at other sites
12) Active HIV, chronic hepatitis B or C infection.
13) 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.
14) Pregnancy or lactation.
15) Major surgical procedure within 28 days prior to the first study treatment.
16) Uncontrolled sustained hypertension
17) Clinically significant (i.e. active) cardiovascular disease
18) History of severe bronchial asthma and/or severe allergy.
19) Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, auto-immune diseases) that may interfere with the planned treatment (i.e. the possibility to receive all six cycles of planned chemotherapy including the concomitant vaccinations), affect patient compliance or place the patient at high risk from treatment-related complications
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method