Drug supply issue

This clinical study aims to explore intrapleural low-dose Visudyne®-mediated photodynamic therapy (photo-induction) as a pathway to promote the uptake of systemically administered Lipoplatin™ in pleural malignancies of patients undergoing video-assisted talcage for their malignant pleural effusions. Photo-induction is expected to overcome the chemo-resistance of pleural malignancies for cisplatin-based chemotherapeutics and thereby improve local tumor control.

The primary objective of the study is to assess the safety and tolerability of intrapleural Visudyne®-mediated photo-induction as a means to selectively increase tumor uptake of systemically administered Lipoplatin™ in patients with primary or secondary pleural malignancies.

The secondary objectives are:

Assessment of treatment efficacy as measured by dyspnea reduction, pleural effusion free survival as well as local relapse rate, progression free and median overall survival.

Analysis of the pleural intratumor penetration of Lipoplatin™ by repeated biopsies for Lipoplatin concentration measurements before and after Visudyne® treatment as well as vessel modulation related parameters (pericyte coverage, vessels morphology).

Inclusion criteria

• Stage IV breast, ovarian, gastric, colorectal, germ cell, lung, bladder, sarcoma or head and neck carcinoma requiring systemic chemotherapy OR alternatively

• Stage I/II malignant pleural mesothelioma OR alternatively

• Stage III/IV mesothelioma requiring systemic chemotherapy OR alternatively

• Stage IVa thymic malignancies AND

• Cytologically proven malignant pleural effusion requiring VATS pleurodesis

• PS 0-1

• Age 18-80

• Written informed content

• Life expectancy >3 months

• Laboratory Requirements - within 28 days prior to enrollment:

• Haematology:

  • absolute granulocytes ≥1× 109/L
  • platelets ≥100 × 109/L
  • leukocytes ≥3 × 109

• Biochemistry:

  • Bilirubin ≤3 × upper limit of normal (<5x if liver metastasis present)
  • AST(SGOT) ≤2.5 × upper limit of normal (<5x if liver metastasis present)
  • Creatinine clearance ≥50 mL/min according to Cockroft and Gault

• No major cardio-pulmonary co-morbidity precluding a surgical approach according to local standards

• Enrollment decision at the institutional multidisciplinary tumor board

• Patient must be willing to use effective methods of contraception. Female patients must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception in addition to either an intrauterine device or hormonal contraception until at least of 3 months after the study treatment. Male patients must agree to use a barrier method (condom) for 3 months after study treatment.

Exclusion criteria

• Grade >2 peripheral neuropathy
• Any concurrent anticancer systemic therapy within 14 days before the study intervention
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study e.g. Known or suspected allergy to the investigational agent or any agent given in association with this trial.

Clinically serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy.

• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Severe interstitial pneumonia or pulmonary fibrosis
• Chronic corticosteroid use at equivalent dose of >30mg/d methylprednisolone
• Pregnancy or breast-feeding
• Porphyria
• Severe liver insufficiency