E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Oral Mucositis (SOM) Associated with Chemoradiotherapy for Locally Advanced, Non-Metastatic Head and Neck Cancer |
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E.1.1.1 | Medical condition in easily understood language |
A sore and inflamed mouth due to chemoradiotherapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Mouth and tooth diseases [C07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028130 |
E.1.2 | Term | Mucositis oral |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of GC4419 administered intravenously (IV) to subjects receiving post-operative or definitive therapy with single-agent cisplatin plus Intensity Modulated Radiation Therapy (IMRT) for locally advanced, non-metastatic squamous cell carcinoma (SCC) of the head and neck.
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E.2.2 | Secondary objectives of the trial |
- To assess the incidence of severe oral mucositis (SOM; World Health Organization Grade 3 or 4) in the study population.
- To observe tumor efficacy outcomes for the study population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Pathologically-confirmed diagnosis of locally advanced squamous cell carcinoma of the head and neck that will be treated with cisplatin plus concurrent IMRT.
Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criteria #2 and #3 below are eligible for the study.
2. Treatment plan to receive a continuous course of IMRT delivered as single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose of 60-72 Gy. Planned radiation fields must include at least 2 oral sites (left and right buccal mucosa, floor of mouth, left and right lateral tongue, soft palate) with each site receiving a cumulative dose of at least 50 Gy.
Note: Unavoidable doses of at least 50 Gy, to include entrance, exit, and scatter doses, still constitute planned radiation.
3. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
4. Treatment plan to receive standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) or weekly (40 mg/m2 for 6-7 doses). The decision on which cisplatin regimen to use in combination with IMRT and GC4419 will be at the discretion of the Investigator.
5. Age 18 years or older
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
7. Adequate hematologic function as indicated by:
- Absolute neutrophil counts (ANC) ≥ 1,500/mm3
- Hemoglobin (Hgb) ≥ 9.0 g/dL
- Platelet count ≥ 100,000/mm3
8. Adequate renal and liver function as indicated by:
- Serum creatinine acceptable for treatment with cisplatin per institutional guidelines
- Total bilirubin ≤ 1.5 x upper-normal limit (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN
9. Serum pregnancy test negative for women of childbearing potential
10. Males and females must agree to use highly effective method of contraception starting prior to the first day of treatment and continuing after the last dose of GC4419 for 30 days (females) or 90 days (males)
11. Properly obtained written informed consent |
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E.4 | Principal exclusion criteria |
1. Metastatic disease
2. Prior radiotherapy to the region of the study cancer or adjacent anatomical sites or more than 25% of total body marrow-bearing area (potentially interfering with chemo-tolerance)
3. Prior induction chemotherapy or plans for chemotherapy to be administered only sequentially, not concurrently, with IMRT
4. Planned concurrent chemotherapy other than single agent cisplatin
5. Receiving any approved or investigational anti-cancer agent other than those provided for in this study
6. Concurrent participation in another interventional clinical study or use of another investigational agent within 30 days of first dose of GC4419
Note: Patients who are participating in non-interventional clinical studies (e.g., QOL, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.
7. Inability to eat soft solid food at baseline for reasons other than mouth soreness after surgery or dental procedures
8. Complete reliance on parenteral or gastrointestinal tube-delivered nutrition at baseline
Note: Patients who have gastrostomy tubes prophylactically placed are eligible. Patients receiving supplemental nutrition through a gastrostomy tube at baseline may be eligible depending on diet.
9. Malignant tumors other than head and neck cancer (HNC) within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating Investigator
10. Active infectious disease excluding oral candidiasis
11. Presence of oral mucositis at baseline. Subjects with mouth or throat pain solely due to postoperative effects are eligible, however.
12. Known history of human immunodeficiency virus (HIV) or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)
13. Female patients who are pregnant or breastfeeding
14. Known allergies or intolerance to cisplatin and similar platinum-containing compounds
15. Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating Investigator, create a risk for a precipitous decrease in blood pressure.
16. Medical history that includes any condition, or requires the use of concomitant medications which, in the Investigator’s judgment, are associated with or create a risk of increased carotid sinus sensitivity, symptomatic bradycardia, or syncopal episodes. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Frequency, duration, and severity of adverse events (AEs) and serious AEs (SAEs);
- Incidence and shifts of clinically significant laboratory abnormalities |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- AEs and SAEs with onset dates on or after the date of enrollment through 30 days following the last dose of GC4419, IMRT or cisplatin (i.e. whichever occurs last) will be recorded on the CRF. All subjects with SAEs will be followed until the events resolve, stabilize, become chronic, the subject completes the study, or the subject is lost to follow-up.
- Clinical laboratory measurements will be conducted at the Screening Visit, twice during Week 1 (once at the Baseline Visit and again on Day 3, 4 or 5), and once weekly from Week 2 through the last day of IMRT. |
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E.5.2 | Secondary end point(s) |
- Cumulative incidence of SOM, defined as any occurrence of WHO Grade 3-4 OM, from the first IMRT fraction through the end of the study treatment period (last day of IMRT)
- Cumulative incidence of WHO Grade 4 OM and days of Grade 4 OM from the first IMRT fraction through the end of the study treatment period (last day of IMRT)
- Cumulative incidence of SOM, and days of SOM, from the first IMRT fraction through two weeks after the end of IMRT
- Tumor outcomes (locoregional failure, distant metastases, progression-free survival, overall survival) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- OM assessments will be completed at the Screening Visit, at the Baseline Visit, twice weekly (no less than two days apart) within each 5-day IMRT period and on the last day of IMRT or Early Termination Visit.
- At the Last Day of IMRT Visit, a clinical tumor assessment will be conducted.
- Subjects will be followed for survival for two years. The subject’s survival status will be assessed at the following time points: Every 3 months, ± 30 days, throughout the 1st year post-IMRT (Months 3, 6, 9, and 12), and Every 4 months, ± 30 days, throughout the 2nd year post-IMRT (Months 16, 20, and 24). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 20 |