Neoplasms

All Conditions

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Antimetabolites

Experimental PCI treatment in dose escalation cohorts consist of Amphinex injection (at different doses) plus a single standard dose of Gemcitabine (1000 mg/m2) plus intraluminal light at the tumour area (at different doses). In addition up to 8 cycles of standard chemotherapy doses of Gemcitabine (1000 mg/m2) and Cisplatin (25 mg/m2) was provided. In the Extended part of the study (last cohort) an additional PCI treatment was introduced at Cycle 5 in the treatment Schedule.

Amphinex administration on day 0, followed by gemcitabine administration (1000 mg/m2) and laser light application (652 nm) on day 4 followed by systemic gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) given on Day 1 and Day 8 of each 21-day cycle, for up to a total of eight cycles. Either one or two PCI treatments (Amphinex, Gemcitabine and intraluminal laser light of 652nm) during the 8 cycles of chemotherapy

Amphinex, Gemcitabine and Cisplatin

Dr Richard Sturgess, MD

This is a Phase I Dose Escalation Study in which the safety, tolerability and efficacy of Amphinex®--induced Photochemical Internalisation (PCI) of Gemcitabine followed by Gemcitabine/Cisplatin Chemotherapy will be assessed in patients with advanced inoperable cholangiocarcinomas.

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma arising from the neoplastic transformation of cholangiocytes, the epithelial cells lining the intra-hepatic and extra-hepatic bile ducts. CCA accounts for about 3% of all digestive tumours and 10-15% of the hepatobiliary tumours. It has an annual incidence of 1-2 cases per 100,000 in the Western World, but rates of CCA have been steadily rising worldwide over the past several decades. On a global scale, CCA is the second most common primary hepatic malignancy These tumours have a poor overall survival with a 5-year survival of about 5%. Over 50% of patients present with advanced-stage disease, and the prognosis is poor with the survival of between 6-12 months for unresected patients, even after biliary decompression. CCA may arise anywhere in the biliary tree, from the small, peripheral hepatic ducts to the distal common bile duct. Commonly used classification systems utilise anatomical location to group tumours into three main categories: intra-hepatic (20-25%), perihilar (also including hilar/Klatskin tumour - 50%) and distal (20-25%).

Hilar CCA is an adenocarcinoma of the extrahepatic biliary tree arising from the main left or right hepatic ducts or their confluence. There has a been a growing recognition that hilar CCA disease actually has a distinct biological behaviour and natural history compared to that of (distal) extra-hepatic CCA, and increasing acknowledgment that different therapeutic strategies are required. At initial presentation of patients with extra-hepatic CCA, 30-50% will have local lymph node involvement and 10-20% metastatic spread typically to the liver and peritoneum. With hilar CCA due to the long asymptomatic course, only 20% are resectable at time of diagnosis.

Standard treatment options for CCA include surgery, radiotherapy and chemotherapy, dependent upon if the CCA is intra- or extra-hepatic. Tumour resection is the only potential cure for CCA. Recent advances in transplantation using stringent selection criteria and utilization of neoadjuvant chemoradiation have demonstrated encouraging results with 5 year survival rates of over 70%, with even one series from The Mayo Clinic yielding a 5-year survival rate of 82%. For the 80% who present with unresectable disease, the utility of these modalities combined with biliary decompression interventions only provided a median survival time of 3-6 months from the time of diagnosis.

For these patients with inoperable advanced CCA the main treatment aim is palliative to relieve local symptoms such as pain and jaundice. Surgery for these patients is primarily for creating a bypass in patients who cannot be stented. CCA is remarkably resistant to pharmacological therapy, but activity has been seen using chemotherapy; mainly gemcitabine given either as monotherapy or paired with either a platin derivative or a fluoropyrimidine as a doublet treatment and more recently docetaxel, these give partial response (PR) rates of 0-9% and an average survival advantage of 2-12 months. Concerning biological therapy, the ongoing studies using sorafenib, lapatinib or bevacizumab have yielded some promising results, with sorafenib demonstrating therapeutic benefit in a single arm Phase II study. For patients who are unsuitable for curative resection, the current systemic combination chemotherapy is with cisplatin plus gemcitabine. This was established in the largest randomized phase III study to date in non-operable biliary tract cancer which demonstrated a response rate of 81.4% and a median overall survival (OS) of 11.7 months; notably there was no statistically significant increase in toxicity when compared to gemcitabine monotherapy. The recent advances in interventional and endoscopic technology have seen a rise in highly specialized centres that are able to deliver very precise local control treatments aimed at gaining local control; these include local ablation and embolization, brachytherapy, radio-frequency ablation and, most significantly, photodynamic therapy which (PDT), with its favourable adverse-event profile, is recommended by most recent review articles for non-resectable patients.

Phase I Dose escalation study With 4 cohorts of different doses of light and fimaporfin (Dose Escalation) plus and additional cohort With one repeated treatment of the dose selected for one treatment (Extended).

A Phase I/II Safety and Efficacy Study of PCI of Gemcitabine and Chemotherapy in Patients With Cholangiocarcinomas

A Phase I/II Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of Amphinex®-Induced Photochemical Internalisation (PCI) of Gemcitabine in Patients With Advanced Inoperable Cholangiocarcinomas

From date of registration to reintervention

Skin photosensitivity - protection information- testing information and events

Local tumour responses by assessment of radiological data

Clinically significant toxicity or abnormal laboratory value assessed as unrelated to the underlying disease, criteria's based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.02:

* Photosensitivity Grade 3 outside the treatment area, except for areas exposed for skin sensitivity tests and areas exposed for re-introduction to normal light. Patient compliance with light protection guidelines MUST be followed; noncompliance will be taken into account
* Phototoxicity Grade 4 inside the treatment area (e.g., duodenal ulceration).
* Non-haematological toxicity (excluding nausea and vomiting) ≥Grade 3.
* Neutropenia or thrombocytopenia Grade 4.
* All other Grade 3 toxicities that are clinically unexpected.

Clinically significant toxicity or abnormal laboratory value assessed as unrelated to the underlying disease criteria's based on the NCI CTCAE version 4.02:

* Photosensitivity Grade 3 outside the treatment area, except for areas exposed for skin sensitivity tests and areas exposed for re-introduction to normal light despite following prescribed precautions. Patient compliance with light protection guidelines MUST be followed; noncompliance will be taken into account
* Clinically significant phototoxicity inside the treatment area (e.g., duodenal ulceration, cholangitis or pancreatitis requiring interventional radiology, operative intervention or would lead to such intervention including events that would have life-threatening consequences)
* A toxicity of any grade that is clinically unexpected and considered related to the PCI treatment (changes to cisplatin treatment alone will not be included as part of this assessment).

PCI Biotech AS

Symptoms and General Pathology

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Disease Attributes

Neoplasms, Squamous Cell

Anti-Infective Agents

Bleomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Drug: Amphinex induced PCI of bleomycin

Intervention:Intravenous administration of Amphinex (day 0) followed by intravenous administration of bleomycin and laser light application (day 4). Laser light application could be both interstitial and/or superficial depending on the tumour location.

Intravenous administration of 0.25 mg/kg Amphinex (day 0) followed by intravenous administration of bleomycin (15000 IU/m2, day 4) and laser light application (3 hours (+/- 1 hour) after bleomycin administration).

Amphinex induced PCI of bleomycin

Baris Karakullukcu, MD

The purpose of this study is to evaluate the efficacy and safety of Amphinex induced PCI of bleomycin ('PC-A11') with superficial and/or interstitial laser light application in patients with recurrent SCCHN.

Approximately 650 000 new cases of head and neck cancer are diagnosed worldwide each year (2). Europe alone, it is estimated that there are approximately 143 000 new cases and more than 68 000 deaths each year (3). The vast majority (\>90%) of head and neck malignancies are squamous cell carcinomas. Most (60-70%) patients with squamous cell carcinoma of the head and neck (SCCHN) present with loco regionally advanced disease.

Standard treatment options for SCCHN include surgery, radiotherapy and chemotherapy. Single-modality treatment with surgery or radiotherapy is generally recommended for the 40% of patients who present stage I or II disease. Each of the two modalities results in similar survival with cure rates ranging between 60% and 90%.

For the 60% of the patients who present with locally advanced disease at diagnosis, combined modality therapy is generally recommended. For patients with unresectable disease the current standard treatment is concurrent cisplatin-based chemoradiation. This is also the standard for patients with resectable disease when organ preservation is desired and, as adjuvant treatment, for patients with high-risk pathological findings at surgical resection.

Despite such an approach, a substantial percentage of patients (20-30%) develop local and/or regional recurrences and distant metastases. Recurrent disease is often not resectable, and even in resectable cases, some patients decline the surgical procedure due to quality of life considerations. Additionally, in recurrent disease the radiation tolerance of the normal tissues makes re-irradiation technically challenging and frequently more toxic than the initial course. The prognosis of patients with recurrent or metastatic SCCHN is generally poor, with a median survival of 6-9 months.

The therapeutic ratio in recurrent SCCHN is narrow. Therefore, there is a large unmet medical need for novel treatments in this patient group, both to lengthen overall survival, and to improve the patients' quality of life.

A Study to Evaluate the Safety and Efficacy of Amphinex Induced PCI of Bleomycin for Recurrent Head and Neck Cancer.

Open-label, Single Arm, Multi-centre, Phase II Study to Evaluate the Safety and Efficacy of Amphinex Induced PCI of Bleomycin With Superficial and Interstitial Laser Light Application in Patients With Recurrent Head and Neck Cancer

The run-in part and expansion part secondary outcome measure

The run-in part and expansion part secondary endpoint

The run-in part and expansion part safety endpoint

The run-in part and expansion part secondary outcome measures

Skin and Connective Tissue Diseases

Breast Neoplasms

Neoplasm Metastasis

Dermatologic Agents

Photosensitizing Agents

The photosensitiser Amphinex is activated by Laser to enhance the effect of Bleomycin

Amphinex

Laser

Martin Forster, MD

The primary goal of this extension study is to further investigate the tolerability and efficacy in a phase I setting in order to see whether lower doses than the initial study dose of 0.25 mg/kg bw Amphinex in Amphinex-based PCI of bleomycin will show a comparable or improved safety and tolerability profile in combination with comparable signs of efficacy.

Use of Amphinex for the enhancement of Bleomycin at the intracellular target. The photosensitizer Amphinex is activated by Laser Light at 652 nm.

Superficial lesions (cutaneous or subcutaneous) was treated with the laser light after administration of Amphinex and Bleomycin according to time scheduled provided.

Safety and preliminary effect data where evaluated at a lower dose than explored in the preceeding dose escalating study with Amphinex.

Dose Escalating Study for Amphinex-based PCI of Bleomycin.

Dose Escalating Study to Evaluate the Tolerability, Efficacy and Safety of Amphinex 0.125 mg/kg or Lower in Amphinex-based PCI of Bleomycin in Patients With Local Recurrence or Advanced/Metastatic, Cutaneous or Sub-cutaneous Malignancies.

Plasma samples for pharmacokinetic (PK) evaluation will be collected from patients and the presence of Amphinex and/or other unidentified metabolites will be assessed using a validated analytical method

Systematic skin photosensitivity tests will be carried out using a white light source with an emission spectrum that, relatively to the luminance and within +/- 50%, excites Amphinex with the same efficiency as sunlight. The luminance will be 500 lux, which is comparable to bright indoor light, and 100.000 lux, which is comparable to direct sunlight. The phototoxic reaction will be scored at specific time points following the light exposure (see the study flowchart Appendix B). This information will be used to predict the degree of photosensitivity of the skin.

Maximal pain during the procedure will be recorded immediately after the procedure on a 10 centimetre visual analogue scale (VAS). Pain will also be recorded 24 hours after the illumination and on day 4. The end-points of the VAS will be "no pain" and "unbearable pain

A formal efficacy analysis is not appropriate for this trial. The response data will be documented by descriptive summary tables. No statistical comparison of dose levels will be done. Fluorescence measurements over time and lesion response evaluation according to RECIST (see Appendix E) will be presented for APT and PP stratified by dose level.

* Summaries of the adverse event rates and laboratory changes from baseline stratified by dose level.
* Listings and frequency tables categorizing laboratory and non-laboratory adverse events by maximum CTCAE toxicity grade and relationship to study drug.
* Pain measurement, fluorescence measurement, skin photosensitivity measurement

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I/II Safety and Efficacy Study of PCI of Gemcitabine and Chemotherapy in Patients With Cholangiocarcinomas	NCT01900158	Cholangiocarcin...	Amphinex, Gemci...	18 Years -	PCI Biotech AS
A Study to Evaluate the Safety and Efficacy of Amphinex Induced PCI of Bleomycin for Recurrent Head and Neck Cancer.	NCT01606566	Recurrent Head ... Carcinoma, Squa...	Amphinex induce...	18 Years -	PCI Biotech AS
A Phase I/II Safety and Efficacy Study of PCI of Gemcitabine and Chemotherapy in Patients With Cholangiocarcinomas	NCT01900158	Cholangiocarcin...	Amphinex, Gemci...	18 Years -	PCI Biotech AS
Dose Escalating Study for Amphinex-based PCI of Bleomycin.	NCT01872923	Cutaneous or Su...	Amphinex Bleomycin Laser	18 Years -	PCI Biotech AS

Spots Global Cancer Trial Database for amphinex

Every month we try and update this database with for amphinex cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for amphinex

Every month we try and update this database with for amphinex cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for amphinex cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.