Trial Title:
Therapeutic Vaccine in Patients With Human Papillomavirus HPV-positive Oropharyngeal Cancer
NCT ID:
NCT06007092
Condition:
Head and Neck Carcinoma
Adult Disease
Conditions: Official terms:
Oropharyngeal Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Within each group, patients will be randomized between poly-ICLC- adjuvanted CD40HVac or
placebo in a 5:1 ratio.
12 patients will be treated at each dose level (10 with vaccine and 2 with placebo).
The patients will receive three subcutaneous injections of a poly-ICLC- adjuvanted
CD40HVac or placebo:
- The first injection will occur at week 0
- The second injection will occur at week 4 (±7 days)
- The third injection will occur at week 24 (±7 days)
Primary purpose:
Treatment
Masking:
Double (Participant, Investigator)
Masking description:
double blinded
Intervention:
Intervention type:
Biological
Intervention name:
HPVDC injection level dose 1
Description:
patient receive 3 injections of vaccine at the same level dose
Arm group label:
level dose 1 HPVDC injection
Intervention type:
Biological
Intervention name:
placebo injection level dose 1
Description:
patient receive 3 injections of vaccine at the same level dose
Arm group label:
level dose 1 placebo injection
Intervention type:
Biological
Intervention name:
HPVDC injection level dose 2
Description:
patient receive 3 injections of vaccine at the same level dose
Arm group label:
level dose 2 HPVDC injection
Intervention type:
Biological
Intervention name:
placebo injection level dose 2
Description:
patient receive 3 injections of vaccine at the same level dose
Arm group label:
level dose 2 placebo injection
Summary:
This study is a multicentric double-blind placebo-controlled dose escalation trial of a
CD40HVac vaccine (humanized anti-CD40 mAb fused to HPV16 E6/E7 oncoproteins) adjuvanted
with poly-ICLC (Hiltonol) in patients with HPV16 oropharyngeal carcinoma with no evidence
of residual or recurrent disease after surgery and/or radiochemotherapy.
The primary objective is to determine the recommended phase 2 dose (RP2D) of a
poly-ICLC(Hiltonol)-adjuvanted CD40HVac vaccine according to the safety and the capacity
to elicit immune responses of different doses Two dose levels of poly-ICLC-adjuvanted
CD40.HVac will be explored
- 1st dose level: CD40.HVac 1.0 mg, with 1.0 mg poly-ICLC
- 2nd dose level: CD40.HVac 3.0 mg, with 1.0 mg poly-ICLC The safety data will be
reviewed by an IDSMB that will give recommendations.
Detailed description:
This study is a multicentric double-blind placebo-controlled dose escalation trial of a
CD40HVac vaccine (humanized anti-CD40 mAb fused to HPV16 E6/E7 oncoproteins) adjuvanted
with poly-ICLC (Hiltonol) in patients with HPV16 oropharyngeal carcinoma with no evidence
of residual or recurrent disease after surgery and/or radiochemotherapy.
The primary objective is to determine the recommended phase 2 dose (RP2D) of a
poly-ICLC(Hiltonol)-adjuvanted CD40HVac vaccine according to the safety and the capacity
to elicit immune responses of different doses Two dose levels of poly-ICLC-adjuvanted
CD40.HVac will be explored
- 1st dose level: CD40.HVac 1.0 mg, with 1.0 mg poly-ICLC
- 2nd dose level: CD40.HVac 3.0 mg, with 1.0 mg poly-ICLC The safety data will be
reviewed by an IDSMB that will give recommendations. Within each group, patients
will be randomized between poly-ICLC- adjuvanted CD40HVac or placebo in a 5:1 ratio.
12 patients will be treated at each dose level (10 with vaccine and 2 with placebo).
The patients will receive three subcutaneous injections of a poly-ICLC- adjuvanted
CD40HVac or placebo:
- The first injection will occur at week 0
- The second injection will occur at week 4 (±7 days)
- The third injection will occur at week 24 (±7 days) Within each dose group, a period
of 7 days must be observed between the first administration of vaccine of the first
patient of the group and the first administration of vaccine/placebo of the second
patient of the group.
A safety monitoring is planned in each dose level group:
- If a grade 5 AE occurs (except if related to cancer) at any time, all vaccinations
will be halted, inclusions in the trial will be suspended and an IDSMB meeting
convened for evaluation
- If a grade 4 AE related to vaccine occurs at any time, inclusions in the trial will
be suspended and an IDSMB meeting convened for evaluation
- If a grade 3 AE related to vaccine occurs at any time and does not resolve or
decrease to grade 1 or baseline after 7 days, inclusions in the trial will be
suspended and an IDSMB meeting convened for evaluation The IDSMB recommendations as
to whether or not to continue the trial after its assessment of the AE will be
transmitted to the Steering Committee and to the sponsor.
Enrolment into the second dose group will open depending on the safety data of the first
dose group during the safety observation period and after IDSMB and Steering Committee
validation. For each patient, this safety observation period begins from the first
administration and stops 2 weeks after the second injection, i.e. at Week 6.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Males and females ≥ 18 years of age.
2. Willing and able to comply with scheduled visits, treatment schedule, laboratory
testing, and other requirements of the study.
3. Subjects with histologically confirmed oropharyngeal squamous cell carcinoma.
4. HPV16 genotyping determined by a specified central reference laboratory with an
established polymerase chain reaction (PCR)- based assay on FFPE archived tumor
biopsies (or 10 slices of 5µm).If local HPV16 genotype assessment has been
performed, the subject can be enrolled if the result shows HPV16 positivity.
Confirmation of HPV16 positive status will be performed retrospectively by the
central laboratory on archived tissue. Formalin- fixed tumour biopsies or surgical
piece before local radical treatment can be optionally available for translational
research.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Comprehensive curative treatment according to the disease stage and national
guidelines, completed at least 16 weeks prior to study drug administration. The
recommended duration between end of curative treatment and study drug administration
is 18 to 20 weeks.
7. No evidence of residual or recurrent disease on the last assessment, comprising a
physical examination, a head and neck CT-scan or a head and neck MRI, and a thoracic
CT Scan (and TEP-scan only for patients traited by radiotherapy or radiochemotherapy
without surgery).
8. Vaccination for Covid and Flu vaccines are authorised 4 weeks before or after the
administration of poly-ICLC-adjuvanted CD40HVac (2 weeks during flu period for the
Flu vaccine)
9. Screening laboratory values must meet the following criteria and should be obtained
within 14 days prior to randomization:
i) White blood cell count (WBC) ≥ 2 x 109/L ii) Absolute neutrophil count (ANC) ≥
1.5 x 109/L iii) Platelets ≥ 100 x 109/L iv) Hemoglobin ≥ 9.0 g/dL v) Serum
creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) > 40
mL/min (using the Cockcroft-Gault formula): Female CrCl = (140 - age in years) x
weight in kg x 0.85/ 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years)
x weight in kg x 1.00 / 72 x serum creatinine in mg/dL vi) Hepatic function: Total
bilirubin ≤ 1.5 x ULN. Subjects with Gilbert's Disease and total bilirubin up to 3 x
ULN may be eligible if total bilirubin< 3.0 mg/dL.Transaminases (ALT and AST) ≤ 3 x
ULN, Alkaline phosphatase ≤ 2.5 x ULN
10. Participants who were born female: negative serum or urine beta human chorionic
gonadotropin (β-HCG) pregnancy test performed before randomisation and on the day of
initial IMP administration (W0)
• Reproductive status: if heterosexually active female, consistently using an
effective method of contraception with partner for sexual activity that could lead
to pregnancy from at least 21 days prior to enrolment through 4 months after the
last administration.
Effective contraception is defined as using any of the following methods:
- Condoms (male or female) with or without a spermicide;
- Intrauterine device (IUD);
- Intrauterine hormone releasing system (IUS);
- Hormonal contraception (progesterone only);
- Successful vasectomy in the male partner (considered successful if a
participant reports that a male partner has (i) documentation of azoospermia by
microscopy, or (ii) a vasectomy more than 2 years ago with no resultant
pregnancy despite unprotected sexual activity postvasectomy);
- Or not be of reproductive potential, such as having reached menopause (no
menses for 1 year without an alternative medical cause) or having undergone
hysterectomy, bilateral oophorectomy, or tubal ligation.
- Agree not to seek pregnancy including through alternative methods, such as
artificial insemination or in vitro fertilization until 4 months after the last
administration.
Participants who were born male, if heterosexually active male, using an effective
method of contraception with their partner from the first day of IMP administration
until 4 months after the last administration. This also applies to sperm donation.
11. Patient should understand, sign, and date the written informed consent form prior to
any protocol-specific procedures performed.
12. Patients must be affiliated to a social security system or beneficiary of the same
Exclusion Criteria:
1. Clinical evidence on physical or radiological examination of residual or recurrent
HPV-driven carcinoma on the primary site, in neck lymph nodes, or in any distant
site metastasis.
2. Any serious or uncontrolled medical disorder that, in the opinion of the
investigator, may increase the risk associated with study participation or study
drug administration, impair the ability of the subject to receive protocol therapy,
or interfere with the interpretation of study results.
3. Subjects with active, known, diagnosed or suspected auto-immune disease. Subjects
suffering from vitiligo, type I diabetes mellitus, residual hypothyroidism due to
autoimmune thyroiditis only requiring thyroid hormone replacement therapy, or
psoriasis not requiring systemic treatment can be enrolled.
4. Patients diagnosed with active interstitial lung disease (ILD)/pneumonitis or a
history of ILD/pneumonitis within the last 5 years, or another condition requiring
immunosuppressive doses of medication such as systemic corticosteroids or absorbed
topical corticosteroids (doses ≥ 10 mg/day prednisone or equivalent) or other
immunosuppressive medications within 14 days of study drug administration. Inhaled
or topical corticosteroids and adrenal replacement doses < 10 mg daily prednisone or
equivalent are permitted.
5. Subjects requiring maintenance treatment with immunosuppressive doses of systemic
corticosteroids. Subjects being treated with a short course of corticosteroids (> 10
mg/day prednisone equivalents) should discontinue this therapy at least 2 weeks
prior to start of study treatment.
6. Prior treatment with therapeutic anti-HPV vaccines.
7. Invasive surgery (defined as surgical intervention requiring general or spinal
anesthesia, and hospital admission) within 28 days prior to start of study
treatment.
8. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus or
hepatitis C virus.
9. Patient with active infection must be postponed until infection resolution
10. Subjects with an uncontrolled or significant heart disease such as long QT syndrome
with QTcF > 480 ms on baseline ECG, NYHA III/IV or uncontrolled arrhythmia.
11. History of organ transplantation, including allogenic peripheral stem cell or bone
marrow transplantation.
12. Participation in another clinical study with an investigational product during the
last 6 months and while on study treatment
13. Vaccination for Covid and Flu vaccines is not permitted within 4 weeks prior the
first vaccination with polyICLC adjuvanted CD40HPVac (2 weeks during flu period for
the Flu vaccine.
14. Treatment is not permitted within 4 weeks prior the first vaccination and 4 months
after the last injection. Furthermore, the use of this medication will be considered
as a deviation to the protocol.
- curative treatment within 12 weeks before the first injection,
- Corticosteroids,
- Live attenuated vaccines (such as measles, mumps, and rubella [MMR]; oral polio
vaccine [OPV]; varicella; yellow fever) or any vaccines that are not live
attenuated (eg, tetanus, pneumococcal, Hepatitis A or B) except IMP vaccine.
- Immunosuppressive medications (Not excluded: [1] corticosteroid nasal spray;
[2] inhaled corticosteroids; [3] topical corticosteroids for mild,
uncomplicated dermatitis; or [4] a single course of oral/parenteral
corticosteroids at doses < 2 mg/kg/day and length of therapy < 11 days with
completion at least 30 days prior to enrollment)
- Blood products
- Immunoglobin
- Anti-tuberculosis drugs
- Immunomodulators (such as cytokines or interferons) or immunosuppressive drugs
during 8 weeks preceding the screening visit and as of 4 months after the last
injection will not be allowed. If any patient needs chronic use of one of these
medicine during this period, the subject will be withdrawn from the
investigational product but should be followed at all visits as planned by the
protocol
- Antipyretic will not be allowed twelve (12) hours before immunization as
preventive treatment of pain or fever.
15. Pregnant or breastfeeding women or intending to become pregnant during study
16. Patient under guardianship or deprived of his liberty by a judicial or
administrative decision or incapable of giving its consent
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94 805
Country:
France
Status:
Recruiting
Contact:
Last name:
Philippe GORPHE, Dr
Phone:
+33 (0)1 42 11 42 11
Email:
philippe.gorphe@gustaveroussy.fr
Contact backup:
Last name:
Caroline EVEN, Dr
Phone:
+33 (0)1 42 11 42 11
Email:
caroline.even@gustaveroussy.fr
Start date:
July 31, 2023
Completion date:
August 2026
Lead sponsor:
Agency:
Gustave Roussy, Cancer Campus, Grand Paris
Agency class:
Other
Collaborator:
Agency:
LinKinVax
Agency class:
Other
Source:
Gustave Roussy, Cancer Campus, Grand Paris
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06007092
