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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01068509




Registration number
NCT01068509
Ethics application status
Date submitted
10/02/2010
Date registered
15/02/2010
Date last updated
11/05/2017

Titles & IDs
Public title
Ovarian Cancer Vaccine for Patients in Remission
Scientific title
A Randomized, Open-label Phase IIb Trial of Maintenance Therapy With a MUC1 Dendritic Cell Vaccine (Cvac™) for Epithelial Ovarian Cancer Patients in First or Second Remission
Secondary ID [1] 0 0
CAN-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epithelial Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Cvac

Experimental: Non-randomized Cvac - Participants received 6-8 intradermal injections of Cvac at 4 sites along both upper arms and both thighs. The 6-8 injections contained \~ 60 × 10\^6 dendritic cells. Following evaluation after the first dose, participants received additional injections as described for the randomized Cvac group below.

Experimental: Randomized Cvac - Participants received 6-8 intradermal injections of Cvac at 4 sites along both upper arms and both thighs every 4 weeks for 24 weeks (7 doses at Weeks 8, 12, 16, 20, 24, 28, and 32), and then every 8 weeks for 24 weeks (3 doses at Weeks 40, 48, and 56). The 6-8 injections contained \~ 60 × 10\^6 dendritic cells.

No intervention: Observational standard of care - Participants in this group did not receive any treatment during the study.


Treatment: Other: Cvac
Cvac consists of autologous dendritic cells (DCs) incubated with the antigen, mannosylated fusion protein (M-FP), to target the DCs to the specific mucin 1 antigen.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival
Timepoint [1] 0 0
Baseline to 48 weeks after the last visit or dose of Cvac (up to 104 weeks)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Baseline to the end of the study (up to 4 years 10 months)
Secondary outcome [2] 0 0
Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104
Timepoint [2] 0 0
Baseline to Week 104
Secondary outcome [3] 0 0
Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104
Timepoint [3] 0 0
Baseline to Week 104

Eligibility
Key inclusion criteria
* Female subjects = 18 years old with histologically confirmed Stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer who have previously undergone surgical cytoreduction and received first or second line conventional chemotherapy and are currently in complete remission (based on clinical and radiologic studies).
* Cancer antigen (CA)-125 = upper limit of normal with a prior history of an elevated CA-125.
* Able and willing to undergo mononuclear cell collection.
* Not more than 12 weeks between enrollment and the last dose of chemotherapy that resulted in complete remission.
* No prior surgery to the peritoneum or pleural space within 28 days of enrollment, excluding removal of catheters used for chemotherapy administration.
* No prior treatment with an investigational product within 30 days of enrollment.
* Baseline electrocardiogram within normal limits or any abnormalities deemed not indicative of cardiac disease for which intervention is required.
* Serum creatinine = 2 mg/dL.
* Serum aspartate aminotransferase or serum alanine aminotransferase = 2.5x the upper limit of normal or serum total bilirubin = 1.5x the upper limit of normal.
* White blood cell count = 3.0 K/µL; absolute neutrophil count = 1.5K/µL; hemoglobin = 9.0 g/dL, and platelets = 100,000/mm^3. (These complete blood count results are required for enrollment. It should be noted that complete blood count results, including monocyte count = 0.2 × 10^9/L, will be needed prior to leukapheresis to determine if sufficient dendritic cells can be obtained for Cvac™ manufacture.)
* Life expectancy of at least 12 months.
* Eastern Cooperative Oncology Group Performance Status of 0-1.
* All toxicities from prior therapies, excluding alopecia, must have resolved to Common Terminology Criteria for Adverse Events Grade = 1.
* Must be non-pregnant and, if of childbearing potential, must use adequate birth control (hormonal or barrier method of birth control or abstinence) for the duration of the study and for 3 months after study completion.
* Able to provide written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Coexisting or other malignancies unless in complete remission for not less than 3 years. Does not include in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin for which no restrictions apply, assuming they have been adequately treated.
* Ovarian germ cell, sarcoma, or mixed Mullerian tumors.
* Prior cancer vaccine or cellular therapy.
* Active uncontrolled infections or any organ system toxicity = Grade 2 by Common Terminology Criteria for Adverse Events criteria.
* Inability to provide informed consent or to comply with study-related procedures.
* Concurrent systemic treatment with steroids or other immunosuppressive agents.
* Diagnosed immunodeficiency and/or autoimmune disorders.
* Myocardial infarction in the past 6 months and/or clinically significant heart disease.
* Infection with human immunodeficient virus (HIV), hepatitis B or C virus.
* Pregnant or breastfeeding.
* Evidence or history of central nervous system metastases.
* Full dose anticoagulation therapy administered within 7 days of leukapheresis procedure.
* Hematopoietic growth factors administered within 14 days of enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2015
Sample size
Target
Accrual to date
Final
63
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [2] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Cetnre - East Melbourne
Recruitment hospital [5] 0 0
Austin Health Cancer Centre - Heidelberg
Recruitment postcode(s) [1] 0 0
4120 - Greenslopes
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Prima BioMed Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety and efficacy of an investigational therapeutic agent (Cvac) in ovarian cancer patients in first or second remission and to determine its ability to prevent cancer from returning.

Study objectives

Primary objectives:

* To confirm the safety of administering Cvac in this population.
* To determine the effects of Cvac on progression-free survival (PFS).

Secondary objectives:

* To determine overall survival (OS) for ovarian cancer patients who receive Cvac after achieving remission in the first or second-line setting.
* Evaluation of host immunologic response to Cvac administration.
Trial website
https://clinicaltrials.gov/study/NCT01068509
Trial related presentations / publications
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.
Grossi M, Quinn MA, Thursfield VJ, Francis PA, Rome RM, Planner RS, Giles GG. Ovarian cancer: patterns of care in Victoria during 1993-1995. Med J Aust. 2002 Jul 1;177(1):11-6. doi: 10.5694/j.1326-5377.2002.tb04616.x.
Ozols RF, Rubin SC, Thomas G, et al. Epithelial ovarian cancer. In: Hoskins WJ, Perez CA, Young RC, eds. Principles and Practice of Gynecologic Oncology, 4th ed. Philadelphia: Lippincott Williams & Wilkins. 2005:919-922.
Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; Southwest Oncology Group; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. 2003 Jul 1;21(13):2460-5. doi: 10.1200/JCO.2003.07.013.
Apostolopoulos V, McKenzie IF. Cellular mucins: targets for immunotherapy. Crit Rev Immunol. 1994;14(3-4):293-309. doi: 10.1615/critrevimmunol.v14.i3-4.40.
Desai J, Mitchell P, Loveland B, et al. A phase I trial of dendritic cells pulsed with MUC1 peptide in patients with solid tumours. Proc ASCO 2002; 21:15b (A1868).
Rustin GJ, Nelstrop AE, Bentzen SM, Bond SJ, McClean P. Selection of active drugs for ovarian cancer based on CA-125 and standard response rates in phase II trials. J Clin Oncol. 2000 Apr;18(8):1733-9. doi: 10.1200/JCO.2000.18.8.1733.
Apostolopoulos V, McKenzie IF, Pietersz GA. Breast cancer immunotherapy: current status and future prospects. Immunol Cell Biol. 1996 Oct;74(5):457-64. doi: 10.1038/icb.1996.76.
Apostolopoulos V, Karanikas V, Haurum JS, McKenzie IF. Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen. J Immunol. 1997 Dec 1;159(11):5211-8.
Meyer T, Rustin GJ. Role of tumour markers in monitoring epithelial ovarian cancer. Br J Cancer. 2000 May;82(9):1535-8. doi: 10.1054/bjoc.2000.1174.
Liu PY, Alberts DS, Monk BJ, Brady M, Moon J, Markman M. An early signal of CA-125 progression for ovarian cancer patients receiving maintenance treatment after complete clinical response to primary therapy. J Clin Oncol. 2007 Aug 20;25(24):3615-20. doi: 10.1200/JCO.2006.09.4540.
Clinical Study Report: A Phase II Trial of Cellular Immunotherapy with M-FP Cancer Vaccine in Subjects with Epithelial Ovarian Cancer, 2007 (with permission from Martin Rogers of Prima Biomed).
Immunotherapy for Prostate AdenoCarcinoma Treatment (IMPACT) Phase 3 study summary of sipuleucel-T in castrate-resistant prostate cancer: http://www.bio-medicine.org/medicine-technology-1/
Austin Research Institute. SOP #811609. Leukapheresis for ex vivo Culture or Human Dendritic Cells for Immunotherapy. V004, 9 January 2004.
Austin Research Institute. SOP #8116 Stages 3-4. Procedures for the ex vivo Generation of MF-P Vaccine Pulsed SC, Phase I Clinical Trial. V006, 10 June 2003.
Gray HJ, Benigno B, Berek J, Chang J, Mason J, Mileshkin L, Mitchell P, Moradi M, Recio FO, Michener CM, Secord AA, Tchabo NE, Chan JK, Young J, Kohrt H, Gargosky SE, Goh JC. Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial. J Immunother Cancer. 2016 Jun 21;4:34. doi: 10.1186/s40425-016-0137-x. eCollection 2016.
Public notes

Contacts
Principal investigator
Name 0 0
Heidi Gray, MD
Address 0 0
University of Washington
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01068509