Clinical trial of Cvac in patients with pancreatic cancer

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2014-000676-26-PL
• Date of registration: 02/09/2014
• Prospective Registration: Yes
• Primary sponsor: Prima BioMed Ltd
• Public title: Clinical trial of Cvac in patients with pancreatic cancer
• Scientific title: A Phase 2 Trial of Cvac (Autologous Dendritic Cells Pulsed with Recombinant Human Fusion Protein [Mucin 1-Glutathione S-Transferase] Coupled to Oxidized Polymannose) in Patients with Resected Stage I or Stage II Adenocarcinoma (Cancer) of the Pancreas
• Date of first enrolment: 20/11/2014
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000676-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Bulgaria, Germany, Poland, Ukraine

Contacts

• Name: Medical Monitor; Holbrook Kohrt MD
• Affiliation: Prima BioMed Ltd

• Name: Medical Monitor; Holbrook Kohrt MD
• Affiliation: Prima BioMed Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Patients may be enrolled if they meet all of the following criteria at screening:
1. Histologically or cytologically diagnosed adenocarcinoma of the pancreas, stage I or stage II disease;
2. Postoperative confirmed R0 or R1 resection status with no evidence of residual disease based on radiographic imaging;
3. CA 19-9 less than 2 × the ULN by the central laboratory;
4. No greater than 6 weeks since completion of prior therapy, which includes surgery with or without radiation or chemotherapy;
5. Mucin 1-positive tumor as determined by central immunohistopathology. Sites will be asked to submit archival tissue (patients may start the study if tissue is available at an outside hospital, but not yet requested or received);
6. Signed an ICF;
7. Willing and able to complete study procedures within the study timelines;
8. Life expectancy of at least 6 months in the investigator’s opinion;
9. = 18 years of age;
10. ECOG performance status < 2 (Karnofsky = 70%);
11. Normal organ and marrow function: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × ULN and serum bilirubin = 1.5 × ULN unless Gilbert’s syndrome has previously been confirmed for the patient, white blood cells (WBCs) = 3.0 K/µL, absolute neutrophil count (ANC) = 1.0 × 109/L, hemoglobin = 8 g/dL, and platelets = 100 × 109/L;
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 Cvac. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Active, acute, or chronic clinically significant infections or bleeding;
2. Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg) or history of congestive heart failure (= Grade 2);
3. Active angina pectoris, stroke, or recent myocardial infarction (within 6 months);
4. Additional uncontrolled, serious medical or psychiatric illness;
5. Evidence or history of central nervous system metastases;
6. Inadequate renal function defined as a creatinine clearance < 60 mL/min as determined by the central laboratory;
7. Additional malignancy diagnosed within 5 years of study enrolment, except carcinoma in situ of the cervix or basal cell and squamous cell carcinomas of the skin;
8. Treatment with any other investigational agent (for any condition) within 4 weeks of screening;
9. Infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis (Treponema pallidum [TPHA]);
10. Concurrent systemic treatment with steroids or other immunosuppressant agents at a dose considered by the investigator to be higher than a standard physiological dose;
11. Active autoimmune disease; any previous autoimmune disease must not require chronic treatment in the 6 months prior to screening.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Maintenance treatment with Cvac in patients with resected stage I or stage II adenocarcinoma (cancer) of the pancreas
MedDRA version: 17.1 Level: PT Classification code 10033609 Term: Pancreatic carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Cvac
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Unknown
Other descriptive name: DC-M-FP
Concentration unit: Other
Concentration type: equal
Concentration number: 60000000-

Primary Outcome(s)

Secondary Objective: Secondary Objectives
• To assess the duration of Progression-Free Survival (PFS) and Overall Survival (OS) following the initiation of Cvac in this patient population

Exploratory Objectives
• To evaluate the time to next treatment (TTNT)
• To evaluate immunologic response to Cvac administration in this patient population
• To investigate biomarkers, including tumor and immune characteristics, of clinical efficacy of Cvac in this patient population
• To assess the change in quality of life (QoL) following the initiation of Cvac in this patient population

Timepoint(s) of evaluation of this end point: See Protocol Table 1 for Schedule of Safety and Tolerability Assessments

Safety and tolerability will be assessed by the following:
• Adverse events evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
• Clinically relevant changes from baseline in vital signs
• Clinically relevant changes from screening in 12-lead ECG
• Clinically relevant changes from baseline in physical examinations
• Clinically relevant changes from baseline in safety laboratory assessments (haematology with differential count, biochemistry, and urinalysis)
• Clinically relevant autoantibody laboratory assessments

Primary end point(s): Safety and Tolerability

Main Objective: To assess the safety and tolerability of Cvac in patients with resected stage I or stage II adenocarcinoma (cancer) of the pancreas

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See Protocol Table 1 for Schedule of Efficacy and Other Assessments

OVERALL SURVIVAL
After documented PD, approximately every 24 weeks for at least 3 years following baseline or until death or the end of the study, investigators will continue to contact patients or caretakers to assess survival.

PROGRESSION-FREE SURVIVAL
Each patient will be assessed for PD at approximately 12 weeks after baseline, and then every 12 weeks thereafter, until PD is determined by the investigator, or until death, or until the end of the study, whichever occurs first. For any patients who progress and continue to receive Cvac, the date and type of response (e.g., stable disease, disease progression) should be collected for any subsequent radiological scans completed.

Secondary end point(s): EFFICACY ENDPOINTS
The efficacy endpoints for this pilot study include OS and PFS.
OS is defined as the number of days between the start date of treatment with Cvac and the date of death from any cause. The duration of OS will be right-censored based on the date the patient was last known to be alive for those who are alive or lost to follow-up as of the data analysis cut off date.

PFS is defined as the number of days between the start date of treatment with Cvac and the earlier of documented disease progression as defined by RECIST criteria or death without prior progression. The date of disease progression or censoring for PFS will be determined according to the conventions listed in the May 2007 FDA Guidance for Industry, ‘Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics’ (www.fda.gov/cder/guidance/7478fnl.htm).

QUALITY OF LIFE
Change from baseline for the following QoL measures:
• European Organization for Research and Treatment of Cancer–Quality of Life Questionnaire (EORTC QLQ-C30, version 3)
• Module QLQ-PAN26

EXPLORATORY ENDPOINTS
• Time to Next Treatment (TTNT)
• Change in immunologic parameters
• Change in CA 19-9
• Change in ECOG performance status
• Change in tumour and immune biomarkers (protein and RNA)

DEFINITIONS
• TTNT is defined as the time from baseline (Week 0) to the date when a next treatment for EOC is started.
• PFS is defined as the time from baseline (Week 0) to the date of the radiological scan used to determine PD or date of death from any cause (PFS event).
• Each patient will be assessed for PD per standard of care at the clinical site, until PD is determined by the investigator, or until death, or until end of study, whichever occurs first for the patient.
• Radiological scans should be performed using the same technique (CT or MRI) throughout the study if possible.
• QoL will be assessed at baseline, after each dose of study agent, and at PFS Follow-Up Visits.

Secondary ID(s)

2014-000676-26-BG

CAN-301

Source(s) of Monetary Support

Prima BioMed Ltd