advanced or recurrent cervical cancer cervical cancer
Conditions
Interventions
Subjects eligible for the study will be assigned to a dose level cohort. All
patients will be treated with AUC 6 Carboplatin and 175 mg/m2 paclitaxel.
Patients will be treated at one of 4 different
Sponsors
ISA Therapeutics B.V.
Eligibility
Age
18 Years to 99 Years
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) 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 (
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints of the study are: • Safety: o Safety will be determined by the incidence rate at each dose level based on the following safety parameters: adverse events (AEs) 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. The safety profile of ISA101b in the bridging cohort(s) will be qualitatively compared to the safety profile observed at the same dose level(s) of ISA101. • HPV-specific immune responses: o 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 (IFNγ-ELISPOT) following injection of the different doses of the ISA101 vaccine. o The HPV-specific immune responses to ISA101b in the bridging cohort(s) will be qualitatively compared to the responses observed at the same dose level(s) of ISA101. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoint: • 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 (with or without bevacizumab) treatment to the documented progression or death from any cause. Exploratory endpoint: • General responsiveness of the immune system as measured by exploratory assays , in particular 1) lymphocyte proliferation as measured by 3H-thymidine incorporation in PBMCs in response to HPV E6/E7 peptides in vitro, 2) antigen-presenting cell (APC) function tests, 3) assay of myeloid and lymphoid cell composition as assessed by flow cytometry and 4) recall proliferative responses of PBMC in response to common microbial antigens as measured by 3H-thymidine incorporation. . | — |
Countries
Netherlands
Outcome results
None listed