Study of the Therapeutic Vaccine (ISA101) to Treat Advanced or Recurrent Cervical Cancer
Conditions
Cervical Cancer
Conditions: official terms
Uterine Cervical Neoplasms
Conditions: Keywords
Advanced or recurrent cervical cancer, HPV16 positive, No curative treatment options
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: ISA101
Type: Drug
Overall Status
Recruiting
Summary
The purpose of the study is to assess the safety, tolerability and to assess the HPV-specific immune responses of different doses of ISA101 vaccine with or without pegylated IFNα as combination therapy with carboplatin and paclitaxel.
Detailed Description
A majority of cervical carcinomas are caused by an uncontrolled, persistent infection with high risk Human Papilloma Virus (HPV). ISA101 is a novel therapeutic synthetic long peptide (SLP) vaccine targeting HPV16 which is being developed and has shown efficacy in patients with high-grade premalignant vulvar lesions caused by HPV with only minor toxicity. For most advanced cancers, chemotherapy remains the treatment modality of choice but has been considered to be immunosuppressive. However, accumulating evidence indicates that many modalities of conventional chemotherapy not only are less immunosuppressive than previously thought but in fact can exert favorable effects on the tumor micro-environment by interfering with suppressive immune cells and by stimulating the release of immune activating molecules by tumor cells. Thus chemotherapy may enhance tumor-specific immunity and synergize with cancer immunotherapy. Addition of pegylated interferon alpha (IFNα) two-b (IIb) to vaccination might even further improve the immune response. This multicenter, open label, non-randomized Phase I/II study will be performed to assess the safety and tolerability of the ISA101 vaccine, and the immune modulating effects of ISA101 with or without pegylated IFNα when combined with carboplatin and paclitaxel.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Female
Criteria: Inclusion Criteria:

1. Women ≥ 18 years of age.

2. Cervical cancer confirmed by histology.

3. Advanced or metastatic or recurrent cervical cancer confirmed by clinical and/or radiological proof with no curative treatment options.

4. Tumour must be HPV16 positive.

5. 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.

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 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 conform the protocol.

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 must be resolved to ≤ grade 2.

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) < 1.5 x 109/L, or platelet count < 100 x 109/L or hemoglobin < 6 mmol/L.

7. Inadequate liver function, defined as:

- Serum (total) bilirubin > 2 x upper normal limit (ULN);

- Aspartate Aminotransferase (ASAT) or Alanine Aminotransferase (ALAT) > 2.5 x ULN (> 5 x ULN in patients with liver metastases);

- 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.

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 who are not on oral contraceptives or do not use effective means of contraception.

12. Pregnancy or lactation. Serum pregnancy test to be performed within 7 days prior to study treatment start in patients of childbearing potential.

13. Major surgical procedure within 28 days prior to the first study treatment.

14. Uncontrolled sustained hypertension (systolic > 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 that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
Locations
UZA
Antwerp, Belgium
Status: Recruiting
Chirec Cancer Institute
Brussels, Belgium
Status: Recruiting
UZG
Gent, Belgium
Status: Recruiting
UZL
Leuven, Belgium
Status: Recruiting
AMC
Amsterdam, Netherlands
Status: Recruiting
NKI/AVL
Amsterdam, Netherlands
Status: Recruiting
UMCG
Groningen, Netherlands
Status: Recruiting
LUMC
Leiden, Netherlands
Status: Recruiting
Radboud UMC
Nijmegen, Netherlands
Status: Recruiting
Start Date
September 2013
Completion Date
January 2016
Sponsors
ISA Pharmaceuticals
Source
ISA Pharmaceuticals
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page