Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL) (VolATIL)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03946358|
Recruitment Status : Not yet recruiting
First Posted : May 10, 2019
Last Update Posted : July 24, 2019
70% all cases of cervical cancer, 95% of anal cancers and about 70% of oropharyngeal cancers are linked to Human Papillomavirus (HPV) infection. HPV oncogenic proteins are trans-activators of telomerase. Indeed, E6 oncoprotein transactivates the human telomerase (hTert). Our group has conducted a clinical trial (NCT02402842) in advanced squamous cell anal cancer (SCCA) and investigators have shown a correlation between the presence of anti-HPV immunity and anti-telomerase T helpher 1 (TH1) CD4 T cell responses, establishing telomerase as an appropriate antigen in HPV-related cancers.
Tumor-reactive CD4+ T cells have been found to ensure efficient effector Cytotoxic T Lymphocytes (CTL) recruitment at the tumor site. Promoting tumor specific TH1 CD4 activation might be an attractive therapeutic option to enhance anti-PD-1/PD-L1 (Programmed cell Death-1/Programmed cell Death-Ligand1) efficacy. However, no option is currently available to expand tumor specific TH1 lymphocytes in most patients. Then, investigators have identified four novel MHC (Major Histocompatibility Complex) class II-restricted peptides derived from human telomerase reverse transcriptase (TERT) referred as "Universal Cancer Peptides" (UCP). UCPVax is a therapeutic cancer vaccine developed by our team and composed of two separate peptides called UCP2 and UCP4 derived from telomerase. This UCPVax vaccine is currently evaluated in a multicenter phase I/II study in Non Small Lung Cancer (NSCLC) (NCT2818426) and seems to show to be safe and immunogenic.
PD-1/PD-L1 immune checkpoint is a relevant candidate target for immunotherapy in HPV+ cancers, based on the prominent role of PD-1 and its ligand PD-L1 in HPV-driven immune-evasion. There is a strong rational of using PD-1 therapy in HPV+ cancers, however anti-PD-1/PD-L1 treatment induces a limited number of long term responses in HPV disease. Combining anti-PD-1/PD-L1 therapy with an antitumor vaccine gains serious consideration in HPV+ cancers. Indeed, anti-cancer vaccines can induce tumor-specific T cells expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses.
So investigators propose to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer vaccine (UCPVax) with atezolizumab in patients with HPV+ cancers by evaluation of the objective response rate at 4 months according to iRecist criteria.
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma of the Head and Neck Anal Canal Cancer Cervical Cancer||Biological: Blood sample collection Procedure: Tumor biopsies Other: CT scan Drug: Atezolizumab Drug: UCPVax||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study Evaluating the Interest to Combine UCPVax a CD4 TH1-inducer Cancer Vaccine and Atezolizumab for the Treatment of Human PapillomaVirus Positive Cancers|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||September 2022|
Experimental: Atezolizumab and UCPVax
Biological: Blood sample collection
Four blood samples will be collected at:
A total of 8 EDTA (ethylenediaminetetraacetic acid) tubes of 6 ml will be collected at each time point to perform:
PBMC collection: 6 EDTA tubes of 6 ml of peripheral blood mononuclear cell [PBMC] will be sent to the central laboratory (Biomonitoring Platform of Besançon, CHRU de Besançon located at Etablissement Français du Sang) at room temperature within 24 hours via an approved carrier for their processing, storage and immunomonitoring analysis. A sending sheet of the samples will be attached to each single sample.
Plasma collection: One 6 ml EDTA tube should be frozen in each investigation center for plasma collection.
Plasma for circulating tumoral DNA (ctDNA) collection: One 6 ml EDTA tube should be frozen in each investigation center for ctDNA collection.
Procedure: Tumor biopsies
A tumor biopsy will be realized and centralized at baseline and at 2 months. Collection of tumor biopsies will be guided by ultrasound or CT scan
Other: CT scan
A CT scan will be planned
Induction phase: Atezolizumab 1200 mg intravenous every 3 weeks since day 1
Boost phase: Atezolizumab 1200 mg intravenous every 3 weeks until disease progression or unacceptable toxicity until disease progression or unacceptable toxicity.
Other Name: anti-PD-L1
Induction phase: UCPVax (combined with Montanide ISA51 as adjuvant) at 1 mg subcutaneously in two separate sites (one site per peptide) at day 1, 8, 15, 29, 36 and 43 (induction phase).
Boost phase: UCPVax boosts vaccine every 6 weeks for the 2 first boosts (boost 1 and boost 2) and then every 9 weeks (boost 3 to boost 5).
Other Name: Vaccine
- Objective response rate at 4 months [ Time Frame: 4 months ]The main objective of this clinical trial is to assess the efficacy of a strategy combining UCPVax and atezolizumab treatment in patients with HPV+ cancer by evaluation of the objective response rate at 4 months according to iRecist.
- Overall survival [ Time Frame: through study completion, an average of 2 years ]Delay from the date of inclusion to death from any cause
- Progression free-survival [ Time Frame: through study completion, an average of 2 years ]Delay from the date of inclusion to the disease progression or death from any cause whichever occurs first
- Health related quality of life (HrQoL) [ Time Frame: From to inclusion patient for maximum of 2 years ]HrQoL will be assessed using EORTC questionnaire (European Organisation for Research and Treatment of Cancer) questionnaire
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03946358
|Contact: Christophe BORG, Pr||+33 (0)3 81 47 99 email@example.com|
|Contact: Laura MANSI, Dr||+33 (0)3 70 63 22 firstname.lastname@example.org|
|CHU de Besançon|
|Contact: Christophe BORG, Pr|
|Centre Georges François Leclerc|
|Contact: Nicolas ISAMBERT, Dr|
|Contact: François-Clément BIDARD, Pr|
|Principal Investigator:||Christophe BORG, Pr||CHU Besançon|