| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locoregional, recurrent head and neck squamous cell carcinoma |
| carcinoma de células escamosas de cabeza y cuello locorregional y recurrente |
|
| E.1.1.1 | Medical condition in easily understood language |
| Recurring head and neck cancer found in tissue near the skin surface, restricted to a localized area |
| cáncer recurrente de cabeza y cuello de un tejido cercano a la piel y en un área localizada |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10060121 |
| E.1.2 | Term | Squamous cell carcinoma of head and neck |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 evaluate the efficacy and safety of ASP-1929 PIT as a monotherapy for the treatment of locoregional, recurrent head and neck squamous cell carcinoma (HNSCC) in patients who have failed or progressed on or after at least two lines of therapy, of which at least one line must be systemic therapy. |
Evaluar la eficacia y la seguridad de la FIT con ASP-1929 en monoterapia para el tratamiento del CCECC locorregional y recurrente en pacientes que han
fracasado o progresado durante o después de al menos dos líneas de tratamiento, de las cuales, al menos, una línea debe ser un tratamiento sistémico. |
|
| E.2.2 | Secondary objectives of the trial |
| Not applicable |
| No procede |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patients with histologically confirmed locoregional persistent, recurrent or second primary squamous cell carcinoma of the Head and Neck, not amenable to curative treatment, including surgery, radiation, or platinum chemotherapy per treatment guidelines.
2. Patient must have failed or progressed on or after at least 2 lines of therapy for squamous cell carcinoma of the head and neck, one of which must be prior systemic platinum-based chemotherapy for treatment of their primary or recurrent head and neck cancer, unless in the opinion of the medical oncologist, the use of platinum-based chemotherapy is contraindicated or not recommended (e.g., renal impairment, allergy to platinum compounds, age, myelosuppression, neuropathy, hearing loss, etc.). Patients who are unable to receive systemic platinum-based chemotherapy should receive an appropriate alternative standard of care systemic therapy for their treatment instead of platinum-based chemotherapy.
a. First-line therapy: The first treatment given for a head and neck cancer. It is often part of a standard set of treatments, such as surgery followed by chemotherapy and radiation, or surgery and radiation, or radiation, or surgery, depending on the stage and location of the head and neck cancer. When used by itself, first-line therapy is the one accepted as the best treatment.
b. Second-line and subsequent lines of therapy: Treatment that is given when initial treatment (first-line therapy and additional lines of therapy) doesn't work or stops working. (e.g. checkpoint inhibitors may be considered if approved and medically indicated).
3. Patients must have completed prior curative radiation therapy for treatment of their head and neck cancer.
4. All locoregional head and neck tumor site(s) are accessible for light illumination treatment.
The accessibility of tumor sites for light illumination treatment must be confirmed by a central radiology review prior to randomization.
5. Target tumors are clearly measurable by contrast enhanced CT scan (or MRI with gadolinium if CT scan is not adequate or the patient has an allergy to CT contrast media).
Measurable disease must be confirmed by central radiology review prior to randomization.
6. Life expectancy > 6 months based on Investigator judgement.
7. Male or female patients at least 18 years old. Female patients must not be pregnant or breastfeeding and must be practicing a medically acceptable form of locally approved birth control, be sterile or post-menopausal. Male patients should be using a medically acceptable form of birth control during the trial or be sterile.
a. Male patients: A male patient must agree to use contraception as detailed in Section 10.4 (Appendix 4 of Protocol) of this protocol during the treatment period and for at least 6 months after the last ASP-1929 infusion and refrain from donating sperm during this period.
b. Female patient: A female patient is eligible to participate if she is not pregnant(see Section 10.4, Appendix 4 of Protocol), not breastfeeding, and at least one of the following conditions applies:
i. Not a woman of childbearing potential (WOCBP) as defined in Section 10.4, Appendix 4 of Protocol
OR
ii. A WOCBP who agrees to follow the contraceptive guidance in Section 10.4, Appendix 4 of Protocol, during the treatment period and for at least 6 months after the last dose of trial intervention and must refrain from breastfeeding for at least 2 months after the last ASP-1929 infusion.
8. Patients must have an ECOG score of 0 – 1.
9. Patients must understand the investigational nature of the trial, be willing to comply with all study procedures and follow-up, and patient or patient’s legal guardian must sign a written informed consent, per local regulations. |
1. Pacientes con carcinoma de células escamosas de cabeza y cuello locorregional, persistente y recurrente o segundo carcinoma primario, no susceptible a tratamiento curativo, lo que incluye cirugía, radioterapia o quimioterapia con platino conforme a las directrices de tratamiento.
2. El paciente no debe haber fracasado o progresado durante o después de al menos 2 líneas de tratamiento para el carcinoma de células escamosas de cabeza y cuello, una de las cuales debe ser quimioterapia sistémica con platino previa para el tratamiento del cáncer de cabeza y cuello primario o recurrente, a menos que, en opinión del oncólogo médico, el uso de quimioterapia con platino esté contraindicado o no esté recomendado (p. ej., insuficiencia renal, alergia a compuestos con
platino, edad, mielosupresión, neuropatía, pérdida de audición, etc.). Los pacientes que no puedan recibir quimioterapia sistémica con platino deben recibir un tratamiento sistémico de práctica clínica habitual y adecuado para su tratamiento, en lugar de la quimioterapia con platino.
a. Tratamiento de primera línea: El primer tratamiento administrado para un cáncer de cabeza y cuello. A menudo forma parte de un conjunto estándar de tratamientos, tales como intervención quirúrgica seguida de quimioterapia y radioterapia, la intervención quirúrgica y radioterapia, la radioterapia o la intervención quirúrgica, dependiendo del estadio y la localización del cáncer de cabeza y cuello. Cuando se usa por sí solo, el tratamiento de primera línea es el aceptado como mejor tratamiento.
b. Tratamiento de segunda línea y líneas posteriores: Tratamiento que se administra cuando el tratamiento inicial (tratamiento de primera línea y líneas adicionales) no funciona o deja de funcionar (p. ej., se puede considerar el uso de inhibidores de puntos de control si están aprobados y médicamente
indicados).
3. Los pacientes deben haber completado la radioterapia curativa anterior para el tratamiento del cáncer de cabeza y cuello.
4. Todas las localizaciones del/de los tumor(es) de cabeza y cuello locorregionales son accesibles para el tratamiento de iluminación con luz. La accesibilidad de las localizaciones del tumor para el tratamiento de iluminación con luz debe confirmarse mediante una revisión central de radiología antes de la aleatorización.
5. Los tumores diana son claramente medibles por TAC con contraste (o RM con gadolinio, si la TAC no es adecuada o el paciente tiene alergia al medio de contraste de la TAC). La enfermedad medible se tiene que confirmar mediante una revisión central de radiología antes de la aleatorización.
6. Esperanza de vida >6 meses, en base al criterio del investigador.
7. Pacientes de ambos sexos de al menos 18 años. Las pacientes no deben estar embarazadas o en periodo de lactancia y deberán utilizar un método anticonceptivo médicamente aceptable y aprobado de forma local, ser estériles o posmenopáusicas. Los pacientes varones deben usar un método anticonceptivo médicamente aceptable durante el ensayo o ser estériles.
8. Los pacientes deben tener una puntuación de ECOG de 0 a 1.
9. Los pacientes deben entender la naturaleza experimental del ensayo, estar dispuestos a cumplir con todos los procedimientos del estudio y el seguimiento y el paciente o el tutor legal del paciente deben firmar un consentimiento informado por escrito, de conformidad con los reglamentos locales. |
|
| E.4 | Principal exclusion criteria |
1. Patients with a history of significant (> or = Grade 3) cetuximab infusion reactions.
2. Patients who have been treated with prior systemic chemotherapy or targeted small molecule therapy or radiation therapy within 2 weeks of trial Day 1 or who have not recovered (ie, < or = Grade 1 or at baseline) from adverse events due to previously administered agent.
3. Patients who have been treated with an anticancer monoclonal antibody therapy within 4 weeks of trial Day 1 or who have not recovered (ie, < or = Grade 1 or at baseline) from adverse events due to previously administered agent.
4. Patients who have been treated with an investigational agent or intervention within 4 weeks of trial Day 1 or who have not recovered (ie, < or = Grade 1 or at baseline) from adverse events, due to previously administered agent or intervention.
5. Present history of distant metastatic disease (M1).
6. Patients who are actively undergoing treatment of or have a diagnosis of an active cancer other than nonmelanoma skin cancer or HNSCC.
7. Tumor in enhanced CT scan invading a major blood vessel (such as the carotid artery) unless the vessel has been embolized, stented or surgically ligated to prevent potential bleeding from a blood vessel (hemorrhage), as confirmed by central radiology review prior to randomization.
8. Patients with a hemoglobin < 9.0 g/dL, WBC < 2000/microL, and platelets < 100 x 10 ^3/microL.
9. Patients with impaired hepatic function defined as alkaline phosphatase (hepatic; alkaline phosphatase [ALP]) > 2 times upper limit of normal, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit of normal, or total serum bilirubin > 2 mg/dL (unless the patient has Gilbert’s disease).
10. Patients with impairment of renal function (Cockcroft-Gault GFR (mL/min/1.73 m^2) < 30).
Cockcroft-Gault GFR Creatinine Clearance Value = {[(140–age) x weight (kg)] / (Scr x 72)} (x 0.85 for females)
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with trial requirements.
12. Patient requires examinations or treatments within 4 weeks after ASP-1929 administration where they would be exposed to significant light (eg, eye examinations, elective surgical procedures) unrelated to the study treatment.
13. Unwilling or unable to follow protocol requirements.
14. Any condition which in the Investigator’s opinion deems the patient an unsuitable candidate to receive study drug.
15. Patients who have been previously treated or randomized to any trial using ASP-1929 or RM-1929 as the study drug. |
1. Pacientes con antecedentes de reacciones importantes (> o = grado 3) a la infusión de cetuximab.
2. Pacientes que han sido tratados con quimioterapia sistémica o tratamientos dirigidos con fármacos de molécula pequeña o radioterapia en las 2 semanas previas al día 1 del ensayo o que no se hayan
recuperado (es decir, ≤< o =grado 1 o nivel inicial) de los acontecimientos adversos debido al fármaco administrado previamente.
3. Pacientes que han sido tratados con un anticuerpo monoclonal antineoplásico en las 4 semanas previas al día 1 del ensayo o que no se hayan recuperado (es decir, < o = grado 1 o nivel inicial) de los
acontecimientos adversos debido al fármaco administrado previamente.
4. Pacientes que han sido tratados con un fármaco o una intervención en investigación en las 4 semanas previas al día 1 del ensayo o que no se hayan recuperado (es decir, < o = grado 1 o nivel inicial) de cualquier acontecimiento adverso debido al fármaco o a la intervención que se administraron previamente.
5. Presentar antecedentes de enfermedad metastásica a distancia (M1).
6. Pacientes que se someten al tratamiento de forma activa para, o tienen un diagnóstico de cáncer activo distinto de cáncer de piel no melanoma o CCECC.
7. Tumor en una exploración por TAC o RM con aumento que revele una invasión de un gran vaso sanguíneo (como la arteria carótida), a menos que el vaso se haya embolizado, se haya colocado un stent o se haya ligado quirúrgicamente para evitar el posible sangrado de un vaso sanguíneo (hemorragia), según se confirme mediante revisión central de radiología antes de la aleatorización.
8. Los pacientes con una hemoglobina <9,0 g/dl, LEU <2000/microl y plaquetas <100 x 10 ^3 /microl.
9. Pacientes con afectación de la función hepática, definida como fosfatasa alcalina (hepática; FA) >2 veces el límite superior de la normalidad, AST o ALT >3 veces el límite superior de la normalidad, o bilirrubina sérica total >2 mg/dl, a menos que el paciente tenga la enfermedad de Gilbert.
10. Pacientes con afectación de la función renal (TFG de Cockcroft-Gault (ml/min/1,73 m ^2 ) <30. Valor del aclaramiento de creatinina según TFG de Cockcroft-Gault = {[ (140–edad) x peso (kg) ]/(S cr x 72) } (x 0,85 para las mujeres).
11. Enfermedad intercurrente no controlada, que incluye, entre otras, la infección en curso o activa, la insuficiencia cardíaca congestiva sintomática, la angina de pecho inestable, la arritmia cardíaca o la
enfermedad psiquiátrica/situaciones sociales que pudieran limitar el cumplimiento de los requisitos del ensayo.
12. El paciente requiere evaluaciones o tratamientos dentro de las 4 semanas posteriores a la administración de ASP-1929, con lo que estaría expuesto a una cantidad de luz significativa (p. ej., exploraciones
oculares, procedimientos quirúrgicos programados) no relacionada con el tratamiento del estudio.
13. Rechazo o incapacidad para seguir los requisitos del protocolo.
14. Cualquier afección que, en opinión el investigador, haga que el paciente no sea considerado un candidato apto para recibir el fármaco del estudio.
15. Pacientes que hayan sido tratados o aleatorizados previamente en cualquier ensayo que utilice ASP-1929 o RM-1929 como fármaco del estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•Progression-Free Survival (PFS)
•Overall Survival (OS) |
•Supervivencia libre de progresión (SLP)
•Supervivencia global (OS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| See Figure 1 in protocol: Patients who continue in the treatment (up to 12 months): every 4 weeks for the first 25 weeks then every 8 weeks for the next 27 weeks. Patients with progressive disease will be moved to long-term follow up and be contacted every 12 weeks |
| Véase la figura 1 del protocolo: lo pacientes que continuen en tratameinto (hasta 12 meses): cada 4 semanas durante las primeras 25 semanas, después cada 8 semanas durante 27 semanas. Los pacientes con progresión de la enfermedad pasarán a seguimiento a largo plazo y serán contactados cada 12 semanas. |
|
| E.5.2 | Secondary end point(s) |
•Objective Response Rate (ORR)
•Complete Response (CR)
• Complete Response by Biopsy (CRb)
• Duration of Response (DoR)
• Event-Free Survivial (EFS)
• Objective unique target and non-target tumor(s) assessment and response rates using CT RECIST 1.1, Choi criteria, and CT tumor volumetrics
• Presence of anti-drug antibodies (ADA)
• Population PK |
•Tasa de respuesta objetiva (TRO)
•Respuesta completa (RC)
• Respuesta completa por biopsia (RCb)
• Duración de la respuesta (DDR)
• Supervivencia libre de enfermedad (SLE)
• Evaluación objetiva de lesiones tumorales diana y no diana y tasa de respuesta mediante RECIST 1.1, criterios Choy y evaluaciones volumétricas del tumor
• Presencia de anticuerpos antifármaco (ADA)
• Farmacocinética |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| See Figure 1 in protocol: Patients who continue in the treatment (up to 12 months): every 4 weeks for the first 25 weeks then every 8 weeks for the next 27 weeks. Patients with progressive disease will be moved to long-term follow up and be contacted every 12 weeks |
| Véase la figura 1 del protocolo: lo pacientes que continuen en tratameinto (hasta 12 meses): cada 4 semanas durante las primeras 25 semanas, después cada 8 semanas durante 27 semanas. Los pacientes con progresión de la enfermedad pasarán a seguimiento a largo plazo y serán contactados cada 12 semanas. |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| 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 |
| Belgium |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Japan |
| Korea, Republic of |
| Netherlands |
| Poland |
| Spain |
| Taiwan |
| 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
|
| LVLS |
| Última visita del último paciente |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 30 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 36 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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