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Squamous Cell Carcinoma of the Head and NeckPhase 2VolATILNCT03946358

Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL)

A Phase 2 study testing Blood sample collection, Tumor biopsies and CT scan in people with Squamous Cell Carcinoma of the Head and Neck and Anal Canal Cancer, run by Centre Hospitalier Universitaire de Besancon at 4 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Blood sample collection, Tumor biopsies and CT scan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
4 sitesFrance
Study dates
18 Feb 2020to 1 Nov 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent
  • Histologically confirmed HPV+ cancers, defined by p16+ (IHC) or HPV genotyping, corresponding to one of the following selected squamous cell carcinoma types:
  • Anal cancer
  • Head and Neck carcinoma,
  • cervical and vulvar carcinoma
  • Locally advanced or metastatic disease
Show all 15Show fewer
  • Pre-treated with at least 1 line of anticancer standard treatment (chemotherapy, radiochemotherapy or targeted therapy…)
  • Age ≥ 18 and ≤ 75 years old
  • Measurable disease defined according to iRECIST v1.1 guidelines (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.)
  • Patients must have a mandatory treatment-free interval of at least 21 days following previous systemic anti-cancer treatments
  • Patients who have received previous systemic anticancer treatment and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 (according to National Cancer Institute [NCI] common terminology criteria for adverse events, version 5 (CTCAE v5) with the exception of Grade 2 alopecia
  • Performance status < 2 (Annex 3)
  • Availability of a pre-treatment tumor sample (archival FFPE [formalin-fixed paraffin-embedded] block) and presence of a tumor lesion suitable for a biopsy
  • Patient affiliated to or beneficiary of French social security system
  • Ability to comply with the study protocol, in the Investigator's judgment.

Who cannot join

  • Non-eligible to a clinical trial:
  • Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy. (HPV vaccination is allowed)
  • Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer
  • Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
  • Current participation in a study of an investigational agent or in the period of exclusion
  • Pregnancy, breast-feeding or absence/refusal of adequate contraception for fertile patients during the period of treatment and for 6 months from the last treatment administration
Show all 41Show fewer
  • Patient under guardianship, curatorship or under the protection of justice
  • Cancer-specific exclusion criteria:
  • Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula
  • Uncontrolled tumor-related pain: exposing patients to risk of exposure to corticoids or iterative hospitalizations. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period
  • Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed
  • Non-eligible to treatment:
  • Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition
  • Active or chronic hepatitis B or C and/or HIV positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus
  • Any immunosuppressive therapy (i.e. corticosteroids >10mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy
  • Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed
  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, (see Annex 5 for a more comprehensive list of autoimmune diseases and immune deficiencies) with the following exceptions:
  • Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study,
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study,
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
  • Rash must cover < 10% of body surface area,
  • Disease is well controlled at baseline and requires only low-potency topical corticosteroids,
  • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months,
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of atezolizumab formulation
  • History of idiopathic or secondary pulmonary fibrosis (History of radiation pneumonitis in the radiation field fibrosis is permitted), or evidence of active pneumonitis requiring a systemic treatment with 28 days before the planned start of study therapy
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
  • 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
  • Patient with intra-alveolar hemorrhage, pulmonary fibrosis, or uncontrolled asthma, or chronic obstructive disease (COPD), defined as at least 1 hospitalization within 4 months prior to enrollment or as at least 3 exacerbations during the last year prior to enrollment
  • Patients requiring oxygen therapy
  • Patients with LEVF (Left Ejection Ventricular Fraction) <40%
  • Hospitalization for cardiovascular or pulmonary disease within 4 weeks prior to enrollment.
  • Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study Note: Patients must agree not to receive live, attenuated influenza vaccine (e.g.,FluMist®) within 28 days prior to randomisation, during treatment or within 5 months following the last dose of atezolizumab
  • Inadequate hematology function: Lymphocyte count at baseline < 800/mm3 ; neutrophil count <1500/mm3, platelets <100000/mm3, Hemoglobin<9g/dL
  • Inadequate hepatic function: bilirubin 2.5 fold ULN (upper limit of normal), AST/ALT (ASpartate Transaminase /ALanine Transaminase) 2.5 fold ULN or 5 fold ULN with liver metastasis, International normalized thromboplastin time ratio >1.5
  • Inadequate renal function: MDRD (Modification of Diet in Renal Disease ) CrCl (Creatinine Clearance) <40ml/min
  • Others inadequate laboratory values: serum albumin<30 g/L; troponin > ULN ; BNP (Brain-Type Natriuretic Peptide) > ULN.
  • Active alcohol or drug abuse.

Trial locations and contacts

4 sites in 1 country.

France4 sites

  • CHU de Besançon

    Besançon

  • Centre Georges François Leclerc

    Dijon

  • Centre Léon Bérard

    Lyon, 69000

  • Hospices Civils de Lyon

    Lyon, 69000

Other trials in France

About this study

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

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.

Read more

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.

Being tested
Blood sample collection, Tumor biopsies, CT scan, Atezolizumab, UCPVax
Keywords
Human PapillomaVirus (HPV), Atezolizumab, Cancer vaccine, Cancer immunotherapy, Telomerase
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Anal Canal Carcinoma, Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood sample collectionBiological

    Four blood samples will be collected at:

    • baseline
    • 2 months from inclusion (+/- 1 week)
    • 4 months from inclusion (+/- 1 week)
    • the end of vaccination visit (+/- 1 week).

    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.

  • Tumor biopsiesProcedure or surgery

    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

  • CT scanOther

    A CT scan will be planned

    • at baseline
    • at tumor evaluation visit (8 weeks)
    • every 8 weeks (+/- 1 week)
    • at end of treatment visit.

  • AtezolizumabDrug

    Also called anti-PD-L1

    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.

  • UCPVaxDrug

    Also called Vaccine

    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).

Study groups in NCT03946358
Study groupRoleWhat they receive
Atezolizumab and UCPVaxExperimentalInduction phase: * Atezolizumab 1200 mg intravenous (IV) every 3 weeks since day 1 * 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) * Atezolizumab 1200 mg IV every 3 weeks until disease progression or unacceptable toxicity until disease progression or unacceptable toxicity.
Receives: Biological: Blood sample collection; Procedure: Tumor biopsies; Other: CT scan; Drug: Atezolizumab; Drug: UCPVax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate at 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.

    Measured: 4 months

Secondary outcomes (4)

  1. Overall survival

    Delay from the date of inclusion to death from any cause

    Measured: through study completion, an average of 2 years

  2. Progression free-survival

    Delay from the date of inclusion to the disease progression or death from any cause whichever occurs first

    Measured: through study completion, an average of 2 years

  3. Health related quality of life (HrQoL)

    Health related quality of life will be assessed using EORTC (European Organisation for Research and Treatment of Cancer) questionnaire

    Measured: From to inclusion patient for maximum of 2 years

  4. Safety of UCPVax in association with anti-PD-L1

    Toxicities graded according to NCI-CTCAE criteria version 5

    Measured: From to inclusion patient for maximum of 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2019
  2. Study start18 Feb 2020
  3. Primary completion1 Mar 2024
  4. Study completion1 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03946358
Sponsor's protocol ID
P/2019/418
Acronym
VolATIL
Status last verified
Nov 2024
First submitted
7 May 2019
Last updated
20 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kim S, Francois E, Andre T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouche O, Desrame J, Zoubir M, Ghiringhelli F, Parzy A, De La Fouchardiere C, Smith D, Deberne M, Spehner L, Badet N, Adotevi O, Anota A, Meurisse A, Vernerey D, Taieb J, Vendrely V, Buecher B, Borg C. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018 Aug;19(8):1094-1106. doi: 10.1016/S1470-2045(18)30321-8. Epub 2018 Jul 2.

    PubMed 30042063

  • Godet Y, Fabre E, Dosset M, Lamuraglia M, Levionnois E, Ravel P, Benhamouda N, Cazes A, Le Pimpec-Barthes F, Gaugler B, Langlade-Demoyen P, Pivot X, Saas P, Maillere B, Tartour E, Borg C, Adotevi O. Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response. Clin Cancer Res. 2012 May 15;18(10):2943-53. doi: 10.1158/1078-0432.CCR-11-3185. Epub 2012 Mar 8.

    PubMed 22407833

  • Dosset M, Godet Y, Vauchy C, Beziaud L, Lone YC, Sedlik C, Liard C, Levionnois E, Clerc B, Sandoval F, Daguindau E, Wain-Hobson S, Tartour E, Langlade-Demoyen P, Borg C, Adotevi O. Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor. Clin Cancer Res. 2012 Nov 15;18(22):6284-95. doi: 10.1158/1078-0432.CCR-12-0896. Epub 2012 Oct 2.

    PubMed 23032748

  • Dosset M, Vauchy C, Beziaud L, Adotevi O, Godet Y. Universal tumor-reactive helper peptides from telomerase as new tools for anticancer vaccination. Oncoimmunology. 2013 Mar 1;2(3):e23430. doi: 10.4161/onci.23430.

    PubMed 23802085

  • Rebucci-Peixoto M, Vienot A, Adotevi O, Jacquin M, Ghiringhelli F, de la Fouchardiere C, You B, Maurina T, Kalbacher E, Bazan F, Meynard G, Clairet AL, Fagnoni-Legat C, Spehner L, Bouard A, Vernerey D, Meurisse A, Kim S, Borg C, Mansi L. A Phase II Study Evaluating the Interest to Combine UCPVax, a Telomerase CD4 TH1-Inducer Cancer Vaccine, and Atezolizumab for the Treatment of HPV Positive Cancers: VolATIL Study. Front Oncol. 2022 Jul 19;12:957580. doi: 10.3389/fonc.2022.957580. eCollection 2022.

    PubMed 35928870

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Blood sample collection, Tumor biopsies and CT scan in people with Squamous Cell Carcinoma of the Head and Neck and Anal Canal Cancer, run by Centre Hospitalier Universitaire de Besancon at 4 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate at 4 months (time frame: 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03946358, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.

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