A study to investigate the efficacy and safety of the PC-A11 treatment in patients with head and neck cancers.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2011-003751-19-GB
• Date of registration: 05/12/2011
• Prospective Registration: Yes
• Primary sponsor: PCI Biotech AS
• Public title: A study to investigate the efficacy and safety of the PC-A11 treatment in patients with head and neck cancers.
• Scientific title: An open-label, single arm, multi-centre, Phase II study to evaluate the safety and efficacy of PC-A11 with superficial and interstitial laser light application in patients with recurrent head and neck squamous cell carcinoma unsuitable for surgery and radiotherapy
• Date of first enrolment: 02/05/2012
• Target sample size: 99
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003751-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Lithuania, Netherlands, Spain, United Kingdom

Contacts

• Name: clinical operations
• Affiliation: Theradex (Europe) Ltd

• Name: clinical operations
• Affiliation: Theradex (Europe) Ltd

Key inclusion & exclusion criteria

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 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 treatable with superficial and/or interstitial laser light application. For superficial lesions: entire tumour accessible 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 43

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 10^9/L, or platelet count <100 x 10^9/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 m

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Recurrent head and neck squamous cell carcinoma (HNSCC) insuitable for surgery and radiotherapy
MedDRA version: 18.0 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Amphinex
Product Code: PC-A11
Pharmaceutical Form: Concentrate for solution for infusion
Other descriptive name: TPCS2a
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: BLEOMYCIN
CAS Number: 11056-06-7

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: 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).

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

Timepoint(s) of evaluation of this end point: The ‘run-in part’ primary endpoint:
3 months after start of treatment

The ‘expansion part’ primary endpoint:
6 months after start of treatment

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The ‘run-in part’ secondary endpoints:
1. 3 months after start of PC-A11 treatment
2. Continuously during 3 months after start of PC-A11 treatment
3. day 0, day1, day 6, day 7, week 4, and week 12
4. day 0, 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. 3 months after start of PC-A11 treatment
7. day 0, day1, day 6, day 7, week 6, and week 12
8. day 0, day 7, week 6, week 12, week 18, week 24, week 36, week 48

Secondary end point(s): The ‘run-in part’ secondary endpoints:
1. To make a preliminary assessment of efficacy at 3 months
2. To assess the safety and tolerability;
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 assess the safety and tolerability;
7. To characterize the pharmacokinetics (PK);
8. To test the Quality of Life (QoL).

Secondary ID(s)

2011-003751-19-DE

PCIA202/10

Source(s) of Monetary Support

PCI Biotech AS

Ethics review

Status: Approved
Approval date:
Contact: