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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01521143




Trial ID
NCT01521143
Ethics application status
Date submitted
17/01/2012
Date registered
25/01/2012
Date last updated
9/12/2016

Titles & IDs
Public title
Cvac as Maintenance Treatment in Patients With Epithelial Ovarian Cancer in Complete Remission Following First-line Chemotherapy or Second-line Treatment
Scientific title
A Randomized Trial of Cvac (Autologous Dendritic Cells Pulsed With Recombinant Human Fusion Protein [Mucin 1-glutathione S-transferase] Coupled to Oxidized Polymannose) as Maintenance Treatment in Patients With Epithelial Ovarian Cancer (EOC) in Complete Remission Following First-line Chemotherapy (A) and Patients With EOC in Second Remission (B)
Secondary ID [1] 0 0
CAN-004
Universal Trial Number (UTN)
Trial acronym
CANVAS
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
Other interventions - Cvac
Other interventions - Placebo

Experimental: Part A - Cvac - Participants received intradermal injections of Cvac given at 4-week intervals for the first 3 doses, and then every 12 weeks for 3 additional doses, for a total of 6 doses over 44 weeks. Each injection had an approximate concentration of 60 × 10^6 viable dendritic cells/mL.

Placebo Comparator: Part A - Placebo - Participants received intradermal injections of placebo given at 4-week intervals for the first 3 doses, and then every 12 weeks for 3 additional doses, for a total of 6 doses over 44 weeks.

Experimental: Part B - Cvac - Participants received intradermal injections of Cvac given at 4-week intervals for the first 3 doses, and then every 12 weeks for 3 additional doses, for a total of 6 doses over 44 weeks. Each injection had an approximate concentration of 60 × 10^6 viable dendritic cells/mL.

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


Other interventions: Cvac
Injections were done at 4 anatomical sites, 1 injection in each of the upper portions of both arms and both thighs.

Other interventions: Placebo
Injections were done at 4 anatomical sites, 1 injection in each of the upper portions of both arms and both thighs.
Placebo consisted of the Cvac formulation buffer (5% HSA, 10% DMSO) with 0.9% simethicone provided in 1 mL vials that had been cryopreserved and stored at the manufacturing facility.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A - Overall Survival - Overall survival was defined as the number of days from Baseline to the date of death from any cause.
Timepoint [1] 0 0
Baseline to the end of the study (up to 3 years, 2 months)
Secondary outcome [1] 0 0
Part A - Time to Next Treatment - Time to next treatment was defined as the number of days from Baseline to the date when the next treatment for epithelial ovarian cancer was started.
Timepoint [1] 0 0
Baseline to the end of the study (up to 3 years, 2 months)
Secondary outcome [2] 0 0
Part A - Progression-free Survival - Progression-free survival was defined as the number of days from Baseline and the documented disease progression as defined by response evaluation criteria in solid tumors (RECIST) or death, whichever occurred earlier. Disease progression was defined as any measurable new lesion(s) that were accurately measured in at least 1 dimension. Any new lesion(s) with a minimum size of 20 mm were deemed as unequivocal (ie, clear or definite) progression. Any new lesion(s) with a minimum size of 15 mm but smaller than 20 mm were considered equivocal progression and had to be confirmed by a follow-up radiological procedure.
Timepoint [2] 0 0
Baseline to the end of the study (up to 3 years, 2 months)
Secondary outcome [3] 0 0
Part B - Overall Survival - Overall survival was defined as the number of days from Baseline to the date of death from any cause.
Timepoint [3] 0 0
Baseline to the end of the study (up to 3 years, 2 months)
Secondary outcome [4] 0 0
Part B - Time to Next Treatment - Time to next treatment was defined as the number of days from Baseline to the date when the next treatment for epithelial ovarian cancer was started.
Timepoint [4] 0 0
Baseline to the end of the study (up to 3 years, 2 months)
Secondary outcome [5] 0 0
Part B - Progression-free Survival - Progression-free survival was defined as the number of days from Baseline and the documented disease progression as defined by response evaluation criteria in solid tumors (RECIST) or death, whichever occurred earlier. Disease progression was defined as any measurable new lesion(s) that were accurately measured in at least 1 dimension. Any new lesion(s) with a minimum size of 20 mm were deemed as unequivocal (ie, clear or definite) progression. Any new lesion(s) with a minimum size of 15 mm but smaller than 20 mm were considered equivocal progression and had to be confirmed by a follow-up radiological procedure.
Timepoint [5] 0 0
Baseline to the end of the study (up to 3 years, 2 months)

Eligibility
Key inclusion criteria
Part A: First Remission

Inclusion Criteria (Part A):

1. Females = 18 years of age at screening with a confirmed diagnosis of Stage III or IV
epithelial ovarian, primary peritoneal, or fallopian tube cancer.

2. Undergone optimal debulking surgery, defined as = 1 cm of residual tumor.

3. Undergone standard platinum and taxane first-line chemotherapy.

4. Signed an informed consent form (ICF).

5. Completed study procedures within the study timelines.

6. Mucin 1-positive tumor as determined by central immunohistopathology.

7. Adequate renal function in the opinion of the investigator based on serum creatinine
and/or glomerular filtration rate.

8. Adequate liver function, defined as serum glutamic oxaloacetic transaminase/aspartate
aminotransferase (SGOT/AST) and serum glutamic pyruvic transaminase/alanine
aminotransferase (SGPT/ALT) = 2× ULN and serum bilirubin = 1.5 × ULN, unless Gilbert's
syndrome had been previously confirmed for the patient.

9. Adequate bone marrow function, defined as white blood cells (WBCs) = 3.0 K/µL,
absolute neutrophil count (ANC) = 1.5 × 109/L, hemoglobin = 9 g/dL, and platelets =
100 × 109/L.

10. Life expectancy of at least 12 months at the time of screening as judged by the
investigator.

11. Not pregnant, and if of childbearing potential, agreed to use a highly effective
method of birth control (implanted, injectable, or oral combination hormonal method
alone or in possible combinations, intrauterine device, vasectomized partner, or
abstinence) prior to study entry, for the duration of the study, and for 3 months
after the last dose of study agent. Male partners of a study patient must use a condom
in addition to the acceptable method of contraception for the female partner, as
specified above.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (Part A):

1. Non-epithelial ovarian cancer, including ovarian germ cell, sarcoma, mixed Müllerian
tumors, or mucinous carcinoma of the peritoneum.

2. Malignancy other than epithelial ovarian cancer, except those that had been in
complete response for a minimum of 3 years, and except carcinoma in-situ of the cervix
or basal cell and squamous cell carcinomas of the skin that had been adequately
treated.

3. Treatment with any investigational product (for any condition) within 4 weeks of
screening.

4. Concurrent systemic treatment with steroids or other immunosuppressant agents at a
dose considered by the investigator to be higher than a standard physiological dose.

5. Evidence of severe or uncontrolled cardiac disease, including myocardial infarction or
unstable angina within 6 months of screening, congestive heart failure, or ventricular
arrhythmias requiring medication.

6. Clinically significant abnormalities as measured by electrocardiogram (ECG).

7. Active uncontrolled infection.

8. Uncontrolled hypertension.

9. Diagnosed immunodeficiency or autoimmune disorder.

10. Infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV), or
active and infectious hepatitis B virus (HBV) infection.

11. Pregnant or lactating.

12. Evidence or history of central nervous system metastasis.

13. Known hypersensitivity to any of the components of the study agent.

14. Active or latent infection with Mycobacterium tuberculosis in any body tissue
(especially renal and/or lung).

15. Any other health condition that would preclude participation in the study in the
judgment of the principal investigator.

Part B: Second Remission

Inclusion Criteria (Part B):

1. Females = 18 years of age at screening with a confirmed diagnosis of epithelial
ovarian, fallopian tube, or peritoneal cancer.

2. Underwent standard cytoreductive surgery and first-line chemotherapy containing
platinum before first relapse and were in complete remission for at least 6 months
prior to relapse.

3. Relapsed once and then underwent standard platinum-based second-line chemotherapy (at
least 3 cycles is required) with or without a second bulk-reducing surgery.

4. Second remission defined as:

1. No definitive evidence of disease (NED) on computed tomography (CT) or magnetic
resonance imaging (MRI) of the abdomen and pelvis;

2. CA-125 = upper limit of normal (ULN) or 90% reduction in CA-125 since start of
second-line chemotherapy;

3. Negative physical exam (ie, no clinical signs).

5. Life expectancy = 3 months in the opinion of the investigator.

6. Signed an informed consent form (ICF).

7. Willing and able to complete study procedures within the expected study timelines.

8. Mucin 1-positive tumor as determined by central immunohistopathology.

9. Histologically documented EOC, fallopian tube, or peritoneal cancer (patients with
pseudomyxoma, mesothelioma, unknown primary tumor, sarcoma, or neuroendocrine
histology, with borderline ovarian cancer, ie, patients with low malignant potential
tumors, and with clear cell or mucinous histology are excluded).

10. Adequate end-organ and hematological function as defined by:

1. Adequate bone marrow function: white blood cells (WBCs) = 3.0 K/µL, absolute
neutrophil count (ANC) = 1.5 × 109/L, hemoglobin = 9 g/dL, and platelets = 100 ×
109/L.

2. Adequate renal function, defined as serum creatinine = 1.5 × ULN.

3. Adequate liver function, defined as serum glutamic oxaloacetic
transaminase/aspartate aminotransferase (SGOT/AST) and serum glutamic pyruvic
transaminase/alanine aminotransferase (SGPT/ALT) = 2 × ULN and serum bilirubin =
1.5 × ULN.

11. Generally well-controlled blood pressure with systolic blood pressure = 140 mmHg and
diastolic blood pressure = 90 mmHg prior to randomization (antihypertensive
medications are permitted). Low-dose chronic hormonal or steroidal treatments are also
permitted.

12. Not pregnant, and if of childbearing potential, agrees to use a highly effective
method of birth control (implanted, injectable, or oral combination hormonal method
alone or in possible combinations, intrauterine device, vasectomized partner, or
abstinence) prior to study entry, for the duration of the study, and for 3 months
after the last dose of study agent. Male partners of a study patient must use a condom
in addition to the acceptable method of contraception for the female partner, as
specified above.

13. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 (applicable at the baseline
visit only).

Exclusion Criteria (Part B):

1. More than 2 previous lines of chemotherapy for EOC, fallopian tube, or peritoneal
cancer.

2. Primary platinum-refractory or platinum-resistant disease (ie, patients who progress
prior to cessation of induction therapy [platinum refractory] or recur within 6 months
after cessation [platinum resistant]).

3. Treatment with any investigational product (for any condition) within 4 weeks of
screening. Enrolled in or has not completed at least 28 days of treatment (prior to
screening) since ending another investigational device or drug treatment, or currently
receiving other investigational treatments.

4. Concurrent systemic treatment with steroids or other immunosuppressant agents at a
dose considered by the investigator to be higher than a standard physiological dose.

5. Evidence of severe or uncontrolled cardiac disease, including myocardial infarction or
unstable angina within 6 months of screening, congestive heart failure, or ventricular
arrhythmias requiring medication.

6. Diagnosed immunodeficiency or autoimmune disorder.

7. Infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV), or
active and infectious hepatitis B virus (HBV) infection.

8. Pregnant or lactating.

9. Evidence or history of central nervous system metastasis.

10. Known hypersensitivity to any of the components of the study agent.

11. Any unresolved persistent toxicities from prior systemic therapy that are either Grade
3 or Grade 4 (except alopecia) per the Common Terminology Criteria for Adverse Events
(CTCAE) version 4.0.

12. Intent to treat patient with both an anti-angiogenesis therapy (such as bevacizumab)
and a poly (ADP-ribose) polymerase (PARP) inhibitor as part of maintenance therapy.
Only one or the other are permitted while the patient is on study and must be started
between the Baseline visit and Visit 1 (first treatment visit) if it will be used as
part of the patient's maintenance therapy regimen.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [2] 0 0
Royal Brisbane and Women`s Hospital - Herston
Recruitment postcode(s) [1] 0 0
- Greenslopes
Recruitment postcode(s) [2] 0 0
- Herston
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
New Jersey
Country [5] 0 0
United States of America
State/province [5] 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
As < 10% of the necessary patients required by the protocol were recruited and the data were
not intended to support a labeling claim, it was determined that the abbreviated clinical
study report (CSR) was the appropriate reporting format. No efficacy analyses were performed
as the trial was terminated early with incomplete enrollment of < 10%.

The purpose of this study is to determine if an investigational cell therapy called Cvac can
help epithelial ovarian cancer (EOC) from returning when administered to patients who are in
complete remission after surgical removal of their tumor followed by standard first-line
(Part A) or second-line (Part B) chemotherapy. Following remission, patients will undergo
leukapheresis for the manufacture of the study agent. After completion of chemotherapy and
confirmation of remission, patients will enter the treatment phase of the study.
Trial website
https://clinicaltrials.gov/show/NCT01521143
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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