Oral Squamous Cell Carcinoma (OSCC)
Conditions
Keywords
neoadjuvant, Nivolumab, anti-PD-1
Brief summary
This is a Phase II, single-centre, non-randomized, single-arm clinical trial to investigate the efficacy and safety of neoadjuvant nivolumab therapy in adult participants with resectable, locoregionally advanced Oral Squamous Cell Carcinoma (OSCC) tumors. Identification of predictive molecular biomarkers of tumor response to treatment will also be performed.
Detailed description
Patients 18 years old and above, any gender, naïve to immunotherapy, and with histologically confirmed T2-4 N0-3 M0 resectable Oral Squamous Cell Carcinoma tumors will be eligible for this clinical trial. Enrolled patients must be fit and eligible for the primary treatment of curative surgery at the primary tumor site with sentinel node identification and removal. Total 60 patients fulfilling eligibility criteria will be included during the period of three years and will receive a total of 2 doses (240 mg per dose) of nivolumab at day 1 and day 15 prior to the curative standard of care surgery. After the study treatment and standard of care surgery, the study participants will be offered evidence-based adjuvant therapy, such as radiotherapy, chemoradiotherapy and checkpoint inhibitors or combination treatments, according to the existing evidence. The study duration per participant after inclusion is approximately 27 weeks including two study-related follow-up visits at 3 and 6 months after the second nivolumab dose. Survival status and disease status of every participant will be also reviewed in medical records at 1, 2, 3 and 5 years after the second nivolumab dose.
Interventions
Nivolumab at day 1 and day 15 prior to the curative standard of care surgery.
Sponsors
Prof. Lars Olaf Cardell
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The subject is willing to participate and has given their written and dated consent to participate in the trial. * Naïve to immunotherapy. ≥ 18 years of age at the time of signing the informed consent. * Primary histologically or cytologically confirmed Oral Squamous Cell Carcinoma classified according to the ICD-10 classification. * Stage T2-4 N0-3 M0. * The subject is planned for curative surgery as the primary treatment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Distant metastases (pathologically proven, radiologic or clinical evidence of distant metastatic disease). This includes all diseases below the clavicles, as well as disease metastatic to the bone, brain, or in the spinal canal. * Active malignancy requiring concurrent treatment or history of another primary malignancy. * History of radio- and/or chemotherapy. * Pregnant, breastfeeding, planning pregnancy or refusal to use highly effective contraception method during the treatment period and for at least 5 months after the last dose. * History of systemic treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. * Prior organ transplantation. * Treatment with a live (attenuated) vaccine within 4 weeks before Screening visit. * Initiation of allergen immunotherapy within 3 months prior Screening visit or a plan to begin therapy during the trial. * Known or suspected systemic hypersensitivity to the active substance nivolumab including any of the OPDIVO™ excipients. * History of systemic hypersensitivity or anaphylaxis to other monoclonal antibodies including any excipient. * Active, known, or suspected autoimmune disease or inflammatory disease (e.g. lupus, inflammatory bowel disease \[e.g. colitis or Crohn's disease\]), diverticulitis, rheumatoid arthritis, Sarcoidosis, Wegener syndrome, Grave's disease, uveitis, etc.) that has required systemic treatment with immune modifying agents in the last 2 years (e.g. replacement therapy such as thyroxine, insulin or physiological corticosteroids is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of response | From start of neoadjuvant treatment to end of neoadjuvant treatment (before surgery), up to approximately 4 weeks | Frequency of tumor response measured as Objective Response Rate (ORR) based on the standard RECIST v1.1 criteria, assessed using radiographic images. |
| Frequency of pathological response | From start of neoadjuvant treatment to end of neoadjuvant treatment (before surgery), up to approximately 4 weeks | Tumour pathological response, defined as percentage residual tumour cells after treatment, measured as Pathologic Complete Response, pCR (no residual tumour cells in tumor bed or lymph nodes), Major Pathological Response, MPR (≤10% residual viable tumour), Pathological Partial Response, pPR (≤50% residual viable tumour). |
| Frequency of volumetric tumour response | From start of neoadjuvant treatment to end of neoadjuvant treatment (before surgery), up to approximately 4 weeks | Volumetric tumour response, measured by radiographic images and/or physical measurements and assessments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-related Adverse events (TRAEs) | From start of neoadjuvant treatment up to and including 6 months. | Incidence of treatment related adverse events classified according to the definitions in NCI CTCAE version 5.0. |
| Incidence of Serious adverse events (SAE) | From start of neoadjuvant treatment up to and including 6 months. | Incidence of serious adverse events |
| Change from baseline in hematology parameters | From screening visit, assessed at regular intervals up to 6 months after first neoadjuvant treatment | Change from baseline in white blood cells (WBC), white blood cell differentiation, absolute neutrophil count (ANC), thrombocytes/platelets, erythrocytes (haematocrit), (B)Erc-MCH, (B)Erc-MCV, haemoglobin (Hb). |
| Change from baseline in clinical chemistry parameters | From screening visit, assessed at regular intervals up to 6 months after first neoadjuvant treatment | Change from baseline in Electrolyte status: sodium (Na), potassium (K), calcium (Ca), creatinine, Liver status: albumin, bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), lactate dehydrogenase (LD), gamma-glutamyl transferase (GGT), Amylase, glucose, and c-reactive protein (CRP). |
| Change from baseline in vital signs | From screening visit up to 6 months after first neoadjuvant treatment | Change in vital signs including heart rate, systolic and diastolic blood pressure, body temperature, respiratory rate. |
| Change from baseline in Electrocardiogram (ECG) values | From screening visit up to 6 months after first neoadjuvant treatment | Change from baseline in ECG values, including ECG QT interval, heart rhythm and rate, ST segment and T wave |
| Rate of postoperative complications | From surgery to date of any postoperative complication, assessed up to 5 months post surgery | Rate of postoperative complications |
| Incidence of surgery delays or surgery cancelation | From start of neoadjuvant treatment to date of surgery, assessed up to 6 months | Incidence of surgery delays/cancellations due to disease progression or treatment related adverse reactions during the neoadjuvant treatment period. |
| Incidence of reduced extent of surgical intervention | At surgery, 3 weeks after start of neoadjuvant treatment | Incidence of reduced extent of surgical intervention with achieved negative/clear surgical margins (SM) or spared from surgery due to complete response to neoadjuvant therapy. |
| Incidence of immunogenicity | From pre-screening to 5 months after surgery | Incidence of immunogenicity as measured by the presence of antidrug antibody (ADA) and neutralizing antibodies (NAb) to nivolumab |
| Proportion of participants with progression-free survival (PFS) and event-free survival (EFS) at distinct timepoints | From second dose of neoadjuvant treatment, assessed one, two, three, four and five years after the second dose of neoadjuvant treatment | Number of patients that had not experienced disease progression (PFS) or any event (EFS) such as recurrence, treatment-related complications, or death at distinct time points. |
| Rate of overall survival at distinct timepoints up to 5-year follow-up | From second dose of neoadjuvant treatment, assessed one, two, three, four and five years after second dose of neoadjuvant treatment. | Number of patients that survived at distinct time points up to 5-year follow-up |
| Effect of neoadjuvant nivolumab treatment on a quality of life (QOL) | From screening visit assessed up to 6 months | Time to clinically relevant changes defined as ≥10-point change for all scales in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC QLQ-H\&N35). |
| Incidence of HPV status in tumour | At pre-screening visit, 1-5 weeks before first neoadjuvant treatment | HPV status assessment of tumor and incidence reporting during pre-screening. |
| Correlation of HPV status and response to neoadjuvant therapy | From pre-screening visit to end of neoadjuvant treatment, up to 8 weeks | Correlation of HPV status and response to neoadjuvant therapy as defined RECIST 1.1 |
| Proportion of patients with response at lymph nodes | From pre-screening to surgery, up to 8 weeks | Lymph node response, according to the RECIST v1.1 criteria |
| Change in the number of metastatic lymph nodes | From prescreening to surgery, up to 8 weeks | Number of metastatic lymph nodes, defined according to the RECIST v1.1 criteria. |
Countries
Sweden
Contacts
CONTACTLars Olaf Cardell, MD, PhD
CONTACTHanna Carstens, MD
Outcome results
None listed