Squamous cell carcinoma of the head and neck MedDRA version: 17.1 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Debio 1143
Product Code: 1143
Pharmaceutical Form: Capsule
INN or Proposed INN: {(5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1
Sponsors
Debiopharm International S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years and over. 2. Newly diagnosed histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx. 3. Patient selected for primary surgical treatment. 4. ECOG PS 0-1. 5. Neutrophil count > 1'500/mm3; platelet count > 75'000/mm3; WBC = 3.0/10-9L; bilirubin or creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Nasopharynx cancer, nasal cavity, and paranasal sinuses carcinomas, recurrent SCCHN. 2. Weight loss of more than 10% in the previous month. 3. Tumour of less than 2 cm in its largest diameter. 4. Distant metastases. 5. Active second malignancy during the last 5 years except non-melanomatous skin cancer or carcinoma in situ of the cervix. 6. Prior treatment with IAP inhibitors and TNF inhibitors. 7. Use or requirement for use of aspirin or aspirin-containing products with > 160 mg of aspirin per day. 8. Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation. 9. Non-compensated liver cirrhosis (Child-Pugh class C). 10. Concomitant treatment with a drug on the prohibited medication list in Section 7.8.2. 11. Patients with known history of uncontrolled or symptomatic angina, arrhythmias or congestive heart failure. 12. If female, pregnant or lactating. 13. Unable to swallow and retain oral medications. 14. Know contraindication to 18F-FDG PET.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the pharmacodynamic activity of Debio 1143, alone or in combination with cisplatin, in patients with squamous cell carcinoma of the head and neck;Secondary Objective: To assess the safety profile of Debio 1143 alone and combined with cisplatin (CDDP). To determine the safety on patient post operative bleeding and wound healing. To assess the ability of to induce cellular apoptosis, and/or tumour necrosis and/or reduce tumour proliferation. To assess any early evidence of biological response as evaluated by 18F-FDG PET; To assess potential effect on immune signalling. To explore plasma PK and tissue levels of Debio 1143 and its metabolite D-1143-MET1. To explore potential PBs ( may include but not limited to DNA alterations, mRNA, and protein levels) that may be predictive of differences in response. To explore genes that may be involved in DMET activity of Debio 1143 to identify potential genetic variations that may be predictive of differences in the PK . To correlate 18F-FDG PET results with PK and PDy if deemed appropriate. ;Primary end point(s): To assess the effect of Debio 1143 and Debio 1143 combined with CDDP on cIAP-1 levels in patients with SCCHN.;Timepoint(s) of evaluation of this end point: At end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Change in vital signs and ECOG PS. 2.Incidence of SAEs. 3.Incidence and severity of AEs graded according to the NCI-CTCAE v4 criteria. 4.Incidence and severity of laboratory abnormalities graded according to the NCI-CTCAE v4 criteria. 5.Rate of severe post-operative bleeding defined as decrease of haemoglobin (Hb) > 2 g/dL and clinical evidence of blood loss (eg, melaena, haematuria or surgical wound bleeding). Each case of Hb decrease > 2 g/dL with iron blood deficiency will be discussed between the Investigator and the Study Medical Monitor to decide whether the observed AE is related or not to post-surgical signs of bleeding. 6. Rate of delayed wound healing defined as presence of surgical wound or surgical wound healing complications at 3-4 weeks from surgery as per the Surgeon's judgment. 7. Assessment of the effect of Debio 1143 alone or combined with CDDP on apoptosis, and/or necrosis and/or proliferation markers in tumours. 8. Measurement of any early biological response to Debio 1143 alone or combined with CDDP by 18F-FDG PET. 9. Assessment of the effect of Debio 1143 alone or combined with CDDP on immune signalling. 10. PK parameters (Cmax, Tmax, AUC, T1/2, Ctrough, Cav, ARCmax, ARAUC, LIAUC, CL/F [only Debio 1143?, V/F [only Debio 1143?) of Debio 1143 alone and its metabolite D-1143-MET1 in plasma. 11. Tumour concentration distribution of Debio 1143 based on MALDI-MS method. 12. PK parameters (Cmax, AUC, CL) of free and total CDDP in plasma. 13. Visual predictive check of relationships between selected PK parameters and PDy and PGx markers. 14. Association of predictive markers with a PDy activity of Debio 1143. 15. Genetic variations in DMET genes associated with differences in the PK disposition of Debio 1143. 16. Exploration of relationships between 18F-FDG PET imaging results and PK/PDy markers if deemed appropriate. ;Timepoint(s) of evaluation of this end point: At end of study | — |
Countries
France
Contacts
Public ContactRegulatory Affairs
Debiopharm International S.A.
Outcome results
None listed