E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oral Mucositis in subjects with head and neck cancer receiving concomitant chemotherapy and radiotherapy |
|
E.1.1.1 | Medical condition in easily understood language |
Swelling and or sores occurring in the mouth due to cancer treatment |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028130 |
E.1.2 | Term | Mucositis oral |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
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 |
The primary objective of the clinical trial is to evaluate the safety and
efficacy of ALD518 in modifying the course of oral mucositis (OM)
in subjects with head and neck cancer (HNC) receiving concurrent
chemotherapy and radiotherapy (CRT). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the clinical trial are to determine the
pharmacokinetics and pharmacodynamics of ALD518 and to evaluate
the impact of ALD518 on health and economic outcomes in subjects
with HNC receiving concurrent CRT. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willing and able to understand and sign an Informed Consent Form (ICF) for the clinical trial approved by the Investigator’s local or a central Institutional Review Board (IRB) or Ethic
Committee (EC)
2. Have recently diagnosed (< than 6 months prior to screening visit date), pathologically confirmed, non-metastatic SCC of the oral cavity, oropharynx, hypopharynx or larynx that will be treated with CRT as first-line treatment; subjects with a history of surgical (approximately 4-6 weeks before RT with sufficient time for post-surgical healing) management are eligible
3. Have a plan to receive a continuous course of conventional external beam irradiation delivered by intensity-modulated radiotherapy (IMRT) as single daily fractions of 2.0 to 2.2 Gy, with a cumulative radiation dose between 55 and 72 Gy at each site. Planned radiation treatment fields must include at least 2 oral sites (retromolar trigone, buccal mucosa, floor of mouth, tongue, or soft palate), with each site receiving ≥ 55 Gy
4. Have a plan to receive a standard cisplatin or carboplatin CT regimen
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
6. CRP < 80 mg/L
7. Have adequate hematopoietic, hepatic, and renal function at the screening visit:
Hematopoietic function
• Hemoglobin ≥ 10 g/dL
• Absolute neutrophil counts (ANC) ≥ 1,500 cells/mm3
• Platelet count ≥ 100 × 10^9/L
Hepatic function
• Total bilirubin ≤ 1.25 times the upper-normal limit (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times the ULN
Renal function: Serum creatinine concentration ≤ 2 mg/dL; if result is ≥ 1.4 mg/dL and ≤ 2.0 mg/dL, a 24-hour urinary creatinine clearance test must be performed by the site’s local laboratory. To be eligible for the clinical trial, a subject must
demonstrate a 24-hour urinary creatinine clearance ≥ 50 mL/min or via Cockcroft-Gault calculation
8. Are not breastfeeding, are not pregnant, and do not plan to become pregnant during the clinical trial
9. Females with childbearing potential must provide a negative pregnancy test within the screening period and must be using adequate contraception (oral or injectable [depot] estrogen, and/or progestogen, or selective estrogen receptor modulator contraceptive therapeutic, intrauterine contraceptive device, or double barrier method [e.g., condom and diaphragm or spermicidal gel]). Non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before clinical trial start
10. Males or females aged 18 years or older |
|
E.4 | Principal exclusion criteria |
1. Tumor of the lips, sinuses, salivary glands, nasopharynx or unknown primary tumor
2. Metastatic disease (M1) Stage IV C
3. Any prior history of head and neck cancer
4. Prior radiation to the head and neck
5. Plan to be treated with cetuximab (Erbitux®)
6. Have undergone induction CT
7. History of non-head and neck malignant tumors, excluding non-melanoma skin cancer or
curatively excised in situ cervical carcinoma within the last 5 years
8. Have had a major surgical procedure, other than for HNC, or significant traumatic injury within 4 weeks prior to the initiation of RT; anticipation of need for a major surgical procedure during the clinical trial
9. Active infectious disease, excluding oral candidiasis
10. Have a previous history, or exposure to active tuberculosis or histoplasmosis infection
11. Have active tuberculosis or histoplasmosis infection
12. Have OM at the screening visit
13. Have a diagnosis of autoimmune disease requiring chronic immunosuppression, e.g. methotrexate
14. Known seropositivity for HIV, HBV or HCV
15. Prior use of ALD518 or other monoclonal antibody
16. Have received any experimental, unregistered therapy (within or outside a clinical trial) within 30 days or five plasma half lives (whichever is longer) before dosing
17. Unable to give informed consent or comply with clinical trial requirements, including completing the subject diary and PRO instruments
18. Have any past or current, acute or chronic concurrent medical condition/illness or therapy that, in the opinion of the Investigator, would make the subject unsuitable for the clinical trial or unable to comply with follow-up visits
19. Subjects who have a history of known symptomatic diverticulosis, diverticulitis, perforated diverticular diseases, or small bowel and/or upper GI perforation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Safety Endpoint
1. Safety and tolerability, including incidence of adverse events
(AEs) and serious adverse events (SAEs), deaths, and clinically significant
laboratory abnormalities
Primary Efficacy Endpoint
1. Clinically assessed ulcerative OM (WHO Grade ≥ 2) at a
cumulative radiation dose of 55 Gy |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Safety Endpoint
1. Safety and tolerability will be assessd from randomization through the 12 month follow-up period.
Primary Efficacy Endpoint
1. Oral mucositis will be assessed from the screening visit through the 4 week post RT treatement period. |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints
1. Secondary efficacy endpoints will be evaluated through the Week
4 Post-RT visit, as appropriate
2. OM Assessments
a. Ulcerative (WHO Grade ≥ 2) and severe (WHO Grade ≥ 3)
OM at cumulative doses of 35 Gy, 45 Gy, 55 Gy and 65
Gy
b. Duration of ulcerative and severe OM
c. Time of onset of ulcerative and severe OM
3. Pain Assessments: Mouth and throat soreness associated with OM
(as measured with OMDQ Question 2)
4. Analgesic Consumption: Use of analgesics, expressed in morphine
equivalents per 24 hours
5. Patient Reported Outcomes (PRO): Patient-reported outcomes
associated with HNC (as measured with the OMDQ and FACTHN)
and FACIT-fatigue scale |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Endpoints
1. N/A
2. Oral mucositis will be assessed from the screening visit through the 4 week post RT treatment period.
3. Pain assessments will be assessed utilizing the OMDQ subject diary from baseline through the 4 week post RT treatment period.
4. Analgesic consumption will be assessed utilizing the OMDQ subject diary from baseline through the 4 week post RT treatment period.
5. Patient Reported Outcomes will be assessed utilizing the OMDQ subject diary, FACT-HN and FACIT-F from baseline through the 4 week post RT treatment period.
|
|
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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Canada |
Germany |
Italy |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
Patients will be followed for 1 year from randomization for survival data. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |