lung cancer non-small cell
Conditions
Interventions
Product Name: UCPVax
Pharmaceutical Form: Solution for injection
Sponsors
Centre Hospitalier Régional Universitaire de Besançon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- Male or female patients, age = 18 and = 89 years old 2- Written informed consent 3- Histologically or cytologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma or other) 4- Stage IIIB not amenable to radiotherapy or stage IV cancer according to the TNM classification (7th edition ref) or recurrent NSCLC after surgery not amenable to loco-regional therapy. 5- Pre-treated with at least 2 lines of systemic treatment (chemotherapy or targeted therapy) with a delay of at least three weeks between the last chemotherapy treatment and the first UCPVax injection, or 3 days after three last tyrosine kinase inhibitor dose and the first UCPVax injection. Chemoradiation for stage IIIB disease is considered as one treatment line. 6- At least one measurable lesion by CT scan or MRI based on RECIST criteria version 1.1 7- Performance status 0 or 1 on the ECOG scale 8- Life-expectancy > 3 months 9- Adequate hematological, hepatic, and renal function: o Hemoglobin = 10.0 g/dL o White blood cells (WBC) = 3.0 x 109/L including neutrophils = 1.5 x 109/L and total lymphocytes count = 1.0 x 109/L o Platelets count = 100 x 109/L o Serum alkaline phosphatase = 3 x ULN in the absence of liver or bone metastases and = 5 x ULN in patients with documented bone or liver metastases o Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] = 2.5 x ULN in the absence of liver metastases and = 5 x ULN in case of liver metastases. o Total bilirubin = 1.5 x ULN o Glomerular Filtration Rate = 60 mL/min (according to Modification of the Diet in Renal Disease [MRDR] formula or Cockroft & Gault formula) o Serum albumin = 30 g/L 10- Effective contraception during the study period and for 1 month after the last study treatment administration. Male patients with a partner at risk of pregnancy should use an appropriate contraception method. 11- Affiliation to French social security or receiving such a regime. 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1- Prior history of other malignancy except for: basal cell carcinoma of the skin, cervical intra-epithelial neoplasia and other cancer curatively treated with no evidence of disease for at least 5 years 2- Symptomatic brain metastases. Patients with controlled brain metastases after radiation therapy or with asymptomatic brain metastases may be included. 3- History of autoimmune diseases (lupus, rheumatoid arthritis, inflammatory bowel disease…) 4- Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (prednisone or prednisolone = 10 mg/day is allowed) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to the start of the study treatment 5- Positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C virus (HCV); presence in the serum of the antigens HBs 6- Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment 7- Pregnancy or lactating patients. 8- Patients with any medical or psychiatric condition or disease, 9- Patients under guardianship, curatorship or under the protection of justice.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I - To estimate the Maximum Tolerated Dose (MTD) and select the Recommended Phase II Dose (RP2D). Phase II - To determine the immunogenicity of UCPVax according to the dose level. ;Secondary Objective: Phase I - To evaluate the acute immunological safety. Phase II - To estimate objective response rates, - To estimate Progression-free survival (PFS) and overall survival, - To evaluate the vaccine-induced CD4 T helper polarization - To assess the efficacy of vaccine according to pre-existing antitumor immune response - To assess health related quality of life - To assess long-term safety ;Primary end point(s): Phase I : Dose Limiting Toxicity (DLT) of UCPVax Phase II : UCP-specific CD4 T cell responses measured in peripheral blood using IFN-? ELISPOT;Timepoint(s) of evaluation of this end point: Phase I : until day 57 Phase II : at baseline, day 29 and prior 1st and 4th boost vaccination and at the end of treatment visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I : - Acute immunological safety measured at baseline, at day 29 (before vaccination n°4) and at day 57 (DLT evaluation): - Routine blood laboratory abnormalities (graded by NCI CTCAE v.4.03) - Circulating auto-antibodies (ANA) - Absolute cell counts of blood lymphocytes subset (B, T, NK) measured by flow cytometry. - Blood abnormalities linked to cytokines release measured by ELISA, (IL-1b, IL-6, IL-8, IL-2, TNFa, IFN-g, IL-17, sCD25) Phase II: - Tumor response evaluated per RECIST v1.1 at day 57 and then every 8 weeks. Objective response rate (ORR) is defined as the addition of complete response (CR) and partial response (PR) rates. Disease control rate is defined as ORR and SD (stable disease). - Progression-free survival (PFS) is defined as the delay from the date of inclusion to the disease progression (RECIST) or death from any cause whichever occurs first, censoring cases without progression at the date of last disease assessment. - Overall survival (OS) is defined as the delay from the date of inclusion to death from any cause. - UCP-specific CD4 T cell polarization measured by intracellular cytokine secretion assay (ICS) and ELISA at baseline, at days 29 and prior 1st and 4th boost vaccination and at the end of treatment visit. - Health related Quality of Life (QoL): EORTC-QLQ-C30 (time to QoL score deterioration). HrQoL will be assessed using EORTC QLQ-C30 and LC13 modules specific to lung cancer at baseline, at days 29 and 57, at each boost vaccine and at the end of treatment visit. - Adverse Events according to NCI CTCAE v.4.03 ;Timepoint(s) of evaluation of this end point: Phase I : at day 29 (before vaccination n°4) and at day 57 Phase II : at day 57 and then every 8 weeks/to the disease progression (RECIST) or death | — |
Countries
France
Contacts
Public ContactChef de projet
DRCI
Outcome results
None listed