p53 Synthetic Long Peptides Vaccine With Cyclophosphamide for Ovarian Cancer

Ovarian Cancer Clinical Trial

— ISA-P53-CTX  

Official title:

p53 Synthetic Long Peptides Vaccine With Cyclophosphamide for Ovarian Cancer a Phase II Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00844506
• Other study ID #: ISA-P53-CTX
• Secondary ID: EUDRACT 2007-007
• Status: Completed
• Phase: Phase 2
• First received: February 13, 2009
• Last updated: February 24, 2011
• Start date: October 2008
• Est. completion date: July 2009

Study information

• Verified date: February 2011
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Ministry of Health, Welfare and Sport
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the addition of cyclophosphamide to the treatment with the p53-SLP vaccine improves clinical efficacy and immunogenicity of the p53-SLP vaccine in ovarian cancer patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent.

• Histological proven epithelial ovarian carcinoma.

• At least 4 weeks after termination of the last course of chemotherapy.

• Rising CA-125 serum levels after "first line" treatment and no measurable disease according to the RECIST (Response Evaluation Criteria in Solid Tumours) criteria, or Rising CA-125 serum levels after "first line" treatment with measurable disease according to the RECIST (Response Evaluation Criteria in Solid Tumours) criteria, but not willing or otherwise not fit to receive "second line" chemotherapy.

• Age 18 years or older, and an life expectancy of at least 3 months.

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

• Performance status 0 to 2 (WHO scale).

• Adequate hepatic, renal, and bone marrow function as defined:

ASAT < 100 U/l; ALAT < 113 U/l; PT 9-12 seconds; APTT 23-33 seconds; creatinine < 135 µmol/l; WBC > 3.0 x 109/L; platelets > 100 x 109/L; hemoglobin > 6.0 mmol/l.

• Adequate venous access for blood collection and i.v. administration of cyclophosphamide.

Exclusion Criteria:

• Pregnancy and / or breast feeding.

• (A)symptomatic cystitis.

• Other malignancies (previous or current), except basal or squamous cell carcinoma of the skin.

• Immunosuppressive agents, except for topical and inhalation corticosteroids.

• Prior therapy with a biological response modifier.

• Any other major disease that may interfere with the conduct of the study (e.g. uncontrolled hypertension, severe and/or unstable heart disease, neurological and psychiatric disorders).

• Signs or symptoms of CNS metastases.

• Known substance abuse (drug or alcohol).

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• P53-SLP vaccine
The P53-SLP vaccine is a vaccine consisting of a total of 10 long (30 amino acids on average length) peptides, covering the p53 protein sequence from amino acid 70 to 251, combined with Montanide ISA51 an adjuvant with a sustained dendritic cell activating ability. Patients will be immunised subcutaneously with the peptide vaccine four times with a three week interval (300µg/peptide).
• Cyclophosphamide
Two days prior to each peptide vaccination, patients will receive 300mg/m2 cyclophosphamide i.v.

Locations

Country	Name	City	State
Netherlands	University Medical Centre Groningen	Groningen

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Center Groningen	Dutch Cancer Society, ISA Pharmaceuticals B.V.

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

Lambeck A, Leffers N, Hoogeboom BN, Sluiter W, Hamming I, Klip H, ten Hoor K, Esajas M, van Oven M, Drijfhout JW, Platteel I, Offringa R, Hollema H, Melief K, van der Burg S, van der Zee A, Daemen T, Nijman H. P53-specific T cell responses in patients with malignant and benign ovarian tumors: implications for p53 based immunotherapy. Int J Cancer. 2007 Aug 1;121(3):606-14. — View Citation

Speetjens FM, Kuppen PJ, Welters MJ, Essahsah F, Voet van den Brink AM, Lantrua MG, Valentijn AR, Oostendorp J, Fathers LM, Nijman HW, Drijfhout JW, van de Velde CJ, Melief CJ, van der Burg SH. Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Clin Cancer Res. 2009 Feb 1;15(3):1086-95. doi: 10.1158/1078-0432.CCR-08-2227. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical responses to the p53 synthetic long peptide vaccine preceded by cyclophosphamide will be assessed by measurement of serum CA-125 levels and CT-scan.		day 105 - 126 after first gift of cyclophosphamide	No
Primary	Immunogenicity will be evaluated by assessing induction and frequency of p53-specific T cells by proliferation and IFN-? ELISPOT.		after fourth immunization	No
Secondary	Safety of the vaccine preceded by cyclophosphamide will be assessed by monitoring the incidence and severity of adverse events using Common Terminology Criteria for Adverse Events v3.0.		durante study	Yes