Study of Volrustomig (MEDI5752) as Sequential Therapy Versus Observation in Participants with Unresected Locally Advanced Head and Neck Squamous Cell Carcinoma, Who Have NotProgressed Following Definitive Concurrent Chemoradiotherapy
- Conditions
- Health Condition 1: C109- Malignant neoplasm of oropharynx,unspecified
- Registration Number
- CTRI/2024/05/067983
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
Inclusion criteria
Screening Part I
In order to allow for pre-cCRT tumor sample collection, Part I Screening procedures may begin before cCRT is initiated.
1. Participant must be 18 years of age, at the time of signing the ICF.
2. Histologically or cytologically documented LA squamous cell carcinoma of the OP, HP, OC, or LX with no evidence of M0.
3. Confirmed unresected Stage III HPV-mediated OPC, ie, T 0-3 N3 M0, or T4 N 0-3 M0; confirmed Stage IVA, IVB HPV-negative OPC/non-OPC, ie, T 1-3 N2 M0, or T4a-b any N, M0 or any T, N3, M0 or select Stage III ie, T3N1 according to the eighth edition of the AJCC staging manual TNM staging system.
4. Confirmation of acceptable FFPE tumor tissue sample to assess PD-L1 expression. Samples must be acquired less than 3 months prior to first dose of cCRT. If such a sample is not available, a fresh tumor biopsy is required.
5. For participants with OPC only: documented HPV status by IHC analysis with CINtec® Histology p16 Assay. If not available, a tumor tissue sample should be collected for testing at the central laboratory.
6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Screening Part I ICF and Screening Part II ICF. Provision of signed and dated written Screening Part I ICF prior to any mandatory study-specific procedures and analyses is required. Before entering Screening Part II, a separate signed and dated written ICF is required. Participants may enter Screening Part II even if the results of the Screening Part I procedures are still pending. If investigators have confirmation of tumor tissue sample availability per tissue sample requirements in Inclusion Criteria 4 and 5, Screening Part I and II ICFs may be signed at the same visit.
Screening Part II
Participants may enter Screening Part II even if the results of the Screening Part I procedures are still pending. Participants are eligible to be randomized to the study only if all of the following Screening Part II inclusion criteria and none of the exclusion criteria apply:
Type of Participant and Disease Characteristics
7. Participants will have completed standard-of-care definitive cCRT with curative intent within 12 weeks 84 days prior to randomization as presented below. If baseline CT, MRI images are equivocal and or residual disease is suspected, investigators are strongly recommended to perform an FDG, PET assessment to confirm absence of progression. Where FDG, PET, avid lesions are detected and accessible, an endoscopy is recommended to be performed and a biopsy taken as clinically indicated to confirm residual disease and evaluate whether participation in this study is appropriate.
a. If cisplatin-based systemic anticancer treatment was administered, participants will have received a cumulative cisplatin dose of 200 mg m2 overall. For example:
High-dose cisplatin for 3 cycles plus concomitant RT
OR
Weekly cisplatin for 6 to 7 cycles plus concomitant RT.
b. If non-cisplatin-based systemic anticancer treatment was administered, participants will have received either:
Carboplatin combined with 5-FU for 3 cycles, plus concomitant RT
OR
Carboplatin combined with paclitaxel for 6 to 7
Exclusion criteria
Exclusion Criteria should be assessed at Screening Part II only. Participants are excluded from the study if any of the following criteria apply
Medical Conditions
1.Histologically, cytologically confirmed head and neck cancer of any other primary
anatomic location in the head and neck not specified in the Inclusion Criteria including participants with squamous cell carcinoma of unknown primary or non-squamous histologies eg, nasopharynx or salivary gland. Participants with 1 primary tumors are not eligible for the study.
2.Participants with any of the following:
a.Residual disease that needs further treatment with curative intent eg, salvage surgery, neck dissection, and RT after definitive cCRT administration per investigators’ assessment and institutional clinical practice;
b. LA-HNSCC that was resected before definitive cCRT
c. LA-HNSCC that was treated and is recurrent at the time of screening.
3.Participants who have received RT alone as definitive local therapy for LA HNSCC.
4.History of another primary malignancy except for
a. T1N0M0 or T2N0M0 HNSCC resected 2 years before the first dose of study intervention with no RT or CTx.
b. Malignancy treated with curative intent with no known active disease 2 years before the first dose of study intervention and of low potential risk for recurrence.
c. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
d. Adequately treated carcinoma in situ without evidence of disease.
e. Cancer participant with incidental histologic findings of prostate cancer that,in the opinion of the investigator, is not deemed to require active therapy eg, incidentalprostate cancer identified following cystoprostatectomy that is TNM Stage pT2N0 may be enrolled.
5. Unresolved toxicities caused by previous anticancer therapy, defined as toxicities other than alopecia and vitiligo not yet resolved to NCI CTCAE Version 5.0 Grade 1 or baseline. Participants with an irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included.eg, hearing loss.
6. As judged by the investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results.
7.Evidence of the following infections:
a.Active infection including TB clinical evaluation that includes clinical history, physical examination, and radiographic findings and TB testing in line with local standard clinical practice.
OR
b. Uncontrolled HIV infection, the following criteria are required to define well-controlled HIV infection.
Undetectable viral RNA load for 6 months,
Cluster of differentiation 4 count of 500 cells µL, stable for at least 6 months on the same anti-HIV medications, and
No history of AIDS (defined by either CD4 T cell count 200 cells µL and or AIDS-defining opportunistic infection.
OR
c Active or uncontrolled HBV or HCV. Participants are eligible if they:
Have controlled HCV viral load defined as undetectable HCV RNA by polymerase chain reaction either spontaneously or in response to a successful prior course of anti-HCV therapy.
Have recei
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method