Trial of Vaccine Therapy in Recurrent Platinum Sensitive Ovarian Cancer Patients

Phase I/II Trial of Vaccine Therapy in Recurrent Platinum Sensitive Epithelial Ovarian Cancer Patients Using Autologous Dendritic Cells Loaded With Amplified Ovarian Cancer Stem Cell mRNA, hTERT and Survivin.

In this study the investigators will include patients with relapsed epithelial ovarian cancer. In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Immunotherapy may have potential for consolidation therapy. Dendritic cell vaccine is well toleranted in previous studies, with minor side effects and no serious adverse events registrated In this study, patients will receive DC-vaccine therapy after response to platinum treatment at relapse. The investigtors include patients in good clinical condition with no severe symptoms of the disease. If patients relapse during vaccine treatment, they will be discontinued from the study.

The investigators have included hTERT- and survivin mRNA in addition to amplified cancer stem cell mRNA in the vaccine.

Study Overview

• Status: Terminated
• Conditions: Recurrent Epithelial Ovarian Cancer
• Intervention / Treatment: Biological: DC-006 vaccine

Detailed Description

Study Period:

• Estimated date of first patient enrolled: First quarter of 2011
• Anticipated recruitment period: 3 years
• Estimated date of last patient completed: First quarter of 2017, follow up to 2022.

Treatment duration:

Patients will receive intradermal immunization once a week for 4 weeks followed by monthly "vaccine boost" during the first year. Patients that show immunological response will continue with vaccination every month the second and third year or as long as there is vaccine available. The patients will have follow up for 5 years or until progression of disease as evaluated by the investigator.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital- Norwegian Radium Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed epithelial ovarian cancer. Histologic documentation of the original primary tumor is required via pathology report.
• Completed first line treatment (surgery and adjuvant or neoadjuvant treatment with carboplatine and paclitaxel)
• Relapsed and platinum sensitive epithelial ovarian carcinoma patients with response to chemotherapy in recurrent disease
• If surgery is indicated, the patient should be surgically treated and then starts vaccination with a minimum interval of 28 days.
• Must be ambulatory with an ECOG performance status 0 or 1.
• Life expectancy ≥ 6 months
• Must be of 18-75 years of age

• Must have lab values as the following:

  • ANC ≥ 1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Hb ≥ 9 g/dL (≥ 5.6 mmol/L)
  • Creatinine ≤ 140 μmol/L (1.6 mg/dL); if borderline, the creatinine clearance ≥ 40 mL/min
  • Bilirubin within the upper limit of normal
  • ASAT and ALAT ≤ 2.5 the upper limit of normal
  • Albumin levels above lower normal value
• If the patient has preserved fertility after primary treatment, she must practice adequate contraception during the study treatment
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

• Eligible to otherwise curative treatment.
• History of prior malignancy, other than ovarian cancer, within the last 5 years, with the exception of curatively treated basal cell carcinoma and cancer in situ cervix uteri.
• Prior surgery within the past 28 days
• Clinical ascites or metastatic pleural fluid
• Active infection requiring antibiotic therapy.
• Have known active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis). Patients with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out brain metastasis.
• Significant cardiac or other medical or mental illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, serious cardiac arrhythmia or psychosis.
• Pregnancy or lactation
• Previous adverse reactions to vaccines such as asthma, anaphylaxis or other serious reactions.
• History of immunodeficiency or autoimmune disease such as but not limited to rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis-dermatomyositis, juvenile onset insulin dependent diabetes, or a vasculitic syndrome.
• Positive for syphilis (treponema pallidum), HIV, Hepatitis B and C tests
• Use of systemic glucocorticoids.
• Prior anti-cancer treatment, including radiotherapy, chemotherapy immunotherapy and/or immunomodulating agents stopped for less than 4 weeks before first study treatment administration. Anti hormonal treatment, such as Tamoxifen, may continue until first study treatment administration.
• Any reason why, in the opinion of the investigator, the patient should not participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DC vaccine; Dendritic cells loaded with amplified ovarian cancer stem cell mRNA, hTERT and Survivin.	Biological: DC-006 vaccine; Vaccine is administered every 4 weeks during the first year. Only patients that show immunological response will continue vaccination every months during the 2nd and 3rd year.; Other Names: Dendritic cell vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of adverse events	Patients are coming every 4 weeks to the site during the 3 years vaccination period and every 6 months during the 5 years follow up period. Biochemistry and hematology results, vital signs and ECOG performance status will be measured at those timepoints during vaccination period.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine immunological response to the vaccine (induction of specific T-cell response)		8, 12 weeks after start of vaccination and every 3 months thereafter
Determine time of disease progression and survival time.	Clinical response will be evaluated via: measurement of CA-125 every 4 weeks; physical examination every 3rd months during vaccination; CT taken every 3rd months during vaccinaton and every 3-6 months during follow up.	Every 4 weeks during vaccination and every 3-6 months during follow up
Treatment free interval	Start date of new antineoplastic therapy since discontinuation of the study will be recorded to capture information regarding treatment free interval.	up to 5 years after vaccination

Collaborators and Investigators

• Sponsor: Steinar Aamdal

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: March 30, 2011
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (ESTIMATE): April 12, 2011

Study Record Updates

• Last Update Posted (ACTUAL): February 26, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Recurrence; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: DC-006