| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent head and neck squamous cell carcinoma (HNSCC) insuitable for surgery and radiotherapy |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067821 |
| E.1.2 | Term | Head and neck cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The ‘run-in part’ primary objective:
• To determine a safe light dose for PC-A11 with interstitial laser light application in patients with recurrent head and neck squamous cell carcinoma unsuitable for surgery and radiotherapy and eligible for interstitial laser light application.
The ‘expansion part’ primary objective:
• To assess the efficacy of PC-A11 with superficial and/or interstitial laser light application in patients with recurrent SCCHN by means of local non-progression rates at 6 months. |
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| E.2.2 | Secondary objectives of the trial |
The ‘run-in part’ secondary objective secondary objectives:
• To make a preliminary assessment of efficacy at 3 months
• To assess the safety and tolerability;
• To characterize the pharmacokinetics (PK);
• To test the Quality of Life (QoL).
The ‘expansion part’ secondary objectives:
• To assess efficacy by means of:
– Local non-progression rate at 3 months;
– Objective Overall Response Rate (ORR);
– Disease Control Rate (DCR);
– Progression Free Survival (PFS);
– Overall Survival (OS);
• To assess the safety and tolerability;
• To characterize the pharmacokinetics (PK);
• To test the Quality of Life (QoL).
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible to participate in this study, patients must meet the following eligibility criteria:
1. Study eligibility reviewed and approved by interdisciplinary hospital team.
2. Age ≥ 18 years.
3. Histologically or cytologically confirmed diagnosis of recurrent or metastatic SCCHN, with or without metastasis considered unsuitable for surgery and radiotherapy (patients with distant or regional metastatic disease may be eligible if local palliation is needed).
4. Performance status (ECOG ≤ 1).
5. At least one measurable target lesion at baseline.
6. Local disease including margins treatible with superficial and/or interstitial laser light application. For superficial lesions: entire tumour assessable for laser light application, treatment margin is 0.5 cm. For interstitial lesions: insertion of implants feasible, treatment margin is 1.0 cm.
7. Estimated life expectancy of at least 12 weeks.
8. Written informed consent.
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| E.4 | Principal exclusion criteria |
Prior Treatment:
1. Local treatment (e.g. surgery or radiation) of their SCCHN by surgery within the previous 4 weeks or by radiation within the previous 3 months.
2. Previous treatment with systemic chemotherapy for their SCCHN within the last 4 weeks.
3. Previous treatment with Photodynamic Therapy within the last 6 months.
4. Prior treatment with bleomycin.
5. Prior treatment with PC-A11.
6. Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) which did not resolve to ≤ grade 2 (as defined by CTCAE version 4.0).
Current Treatment:
7. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another investigational study.
8. Other concurrent anticancer therapies.
9. Treatment with a medicinal product with known or potential drug-drug interaction with bleomycin or Amphinex.
Haematology, coagulation and biochemistry:
10. Inadequate bone marrow function:
• Absolute Neutrophil Count (ANC): < 1.5 x 109/L, or platelet count <100 x 109/L or haemoglobin < 6 mmol/L.
11. Inadequate liver function, defined as:
• Serum (total) bilirubin > 2 x the Upper Limit of Normal (ULN) for the institution.
• Aspartate Amino Transferase (ASAT) or Alanine Amino Transferase (ALAT) > 2.5 x ULN.
• Alkaline phosphatase levels > 2.5 x ULN.
12. Glomerular filtration rate (GFR) < 30ml/min.
13. Clinical significant electrolyte abnormalities (Potassium, Magnesium, Phosphate that is greater than CTCAE grade 3 for both low and high values)
Other:
14. Tumours known or suspected to be eroding into the dura mater or a major blood vessel, e.g. carotid artery (interna and /or communis) in or adjacent to the illumination site (minimum distance between tumour tissue and critical structure should be 0.5 cm for superficial tumours and 1.0 cm for interstitial tumours).
15. Nasopharyngeal carcinoma.
16. Conditions contraindicated for bleomycin treatment (current lung infection, severely impaired pulmonary function) excluded by lung function test (either formal lung function test for patients able to undertake such assessment, or a suitable opinion by an appropriately trained Respiratory / Anaesthetic Clinical Specialist).
17. Conditions that worsen when exposed to light (including porphyria).
18. Inability to undergo CT or MRI.
19. Pregnancy or lactation (female patients with childbearing potential). Serum pregnancy test to be performed within 7 days prior to study PC-A11 treatment start, or within 14 days followed by a confirmatory urine pregnancy test within 7 days prior to study treatment start.
20. For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients who are not surgically sterile or with female partners of childbearing potential: absence of highly effective method of contraception resulting in a low failure rate (i.e. less than 1% per year). These methods of contraception according to the note for guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP/ICH/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence and vasectomy. Note: Abstinence is only acceptable as true abstinence: when this is in line with the preferred and usual lifestyle of the subject, periodic abstinence (eg calender, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
21. Planned surgery, endoscopic examination or dental treatment in first 30 days after PC-A11 treatment.
22. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PC-A11 treatment.
23. Congestive heart failure NYHA Class III and IV. Cardiac arrhythmias (except for atrioventricular block type I, Mobitz type II, and Wenckebach type) signs and symptoms of relevant cardiovascular disease.
24. Known allergy or sensitivity to photosensitisers.
25. Ataxia telangiectasia
26. Concomitant malignant disease, with exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix.
27. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the planned PC-A11 treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The ‘run-in part’ primary endpoint:
Dose-limiting toxicities (DLT) and the safety profile of PC-A11 in patients undergoing interstitial laser light application
The ‘expansion part’ primary endpoint:
The proportion of patients with non-progressive local disease 6 months after start of PC-A11 treatment assessed according to modified RECIST 1.1 criteria
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The ‘run-in part’ primary endpoint:
- 4 week (DLT assessment)
-3 months (overall safety profile)
The ‘expansion part’ primary endpoint:
6 months after start of treatment |
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| E.5.2 | Secondary end point(s) |
The ‘run-in part’ secondary endpoints:
1. The proportion of patients with non-progressive local disease 3 months after start of PC-A11 treatment assessed according to modified RECIST 1.1 criteria.
2. PFS defined as the time from start of PC-A11 treatment to the documented progression or death from any cause.
3. To characterize the pharmacokinetics (PK);
4. To test the Quality of Life (QoL).
The ‘expansion part’ secondary endpoints:
1. To assess efficacy by means of Local non-progression rate at 3 months;
2. To assess efficacy by means of Objective Overall Response Rate (ORR);
3. To assess efficacy by means of Disease Control Rate (DCR);
4. To assess efficacy by means of Progression Free Survival (PFS);
5. To assess efficacy by means of Overall Survival (OS);
6. To characterize the pharmacokinetics (PK);
7. To test the Quality of Life (QoL).
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
The ‘run-in part’ secondary endpoints:
1. 3 months after start of PC-A11 treatment
2. Timepoint for progression or death
3. day 0, day1, day 6, day 7, week 4, week 8 and week 12
The ‘expansion part’ secondary endpoints:
1. 3 months after start of PC-A11 treatment
2-3. 12 months after start of PC-A11 treatment
4 -5. time of death
6. day 0, day1, day 6, day 7, week 6, and week 12
7. day 0, day 7, week 6, week 12, week 18, week 24, week 36, week 48
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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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 | 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
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| End of trial is last subject last visit |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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