| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locoregional, recurrent head and neck squamous cell carcinoma |
|
| 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 |
|
| 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 | 21.0 |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
|
| 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.
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, liver disease, 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 therapy: Treatment that is given when initial treatment (first-line therapy) doesn't work or stops working.
3. Patients must have completed prior curative radiation therapy for treatment of their head and neck region.
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. |
|
| E.4 | Principal exclusion criteria |
1. Patients with a history of significant (≥ 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, ≤ 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, ≤ 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, ≤ 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 or MRI 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).
8. Patients must have a Hemoglobin ≥ 9.0 g/dL, WBC ≥ 2000/μL, and Platelets ≥ 100 x 10³/μL.
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 (patients with Gilbert's disease will be excluded if they have a bilirubin ≥ 5 mg/dL).
10. Patients with impairment of renal function (Cockcroft-Gault GFR (mL/min/1.73 m²) < 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•Progression-Free Survival (PFS)
•Overall Survival (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 |
|
| 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 1.1with modifications, Choi criteria with modifications, and CT tumor volumetrics
• Presence of anti-drug antibodies (ADA)
• Population PK
|
|
| 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 |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 |
| Greece |
| Japan |
| Korea, Republic of |
| 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
|
|
| 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 | 36 |
| 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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