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

• Status: Completed
• Trial end date: 2019-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PCI Biotech AS
• Treatments: Cisplatin; Gemcitabine

Criteria

Inclusion Criteria:

1. Histopathologically/cytologically (C5) verified adenocarcinoma consistent with cholangiocarcinoma

2. Cholangiocarcinoma that:

• Is considered to be inoperable

• Has a primary lesion in the perihilar biliary duct region that requires stent placement

• Has nodal enlargement ≤ to N1 as per CT/MRI assessment

• If has metastatic disease; this should be confined to the liver parenchyma only

3. Adequate biliary drainage (either at least 50% of the liver volume, or at least two sectors), with no evidence of active uncontrolled infection (patients on antibiotics are eligible).

4. Age ≥ 18 years.

5. Performance status ECOG ≤ 1.

6. Estimated life expectancy of at least 12 weeks.

7. Written informed consent.

Exclusion Criteria:

1. Any prior anti-cancer (either local or systemic) treatment for cholangiocarcinoma.

2. Patients with extra-hepatic metastatic cholangiocarcinoma.

3. Patients with a severe visceral disease other than cholangiocarcinoma.

4. Patients with primary sclerosing cholangitis.

5. Patients with porphyria or hypersensibility to porphyrins.

6. Patients with an active second primary cancer, 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. An active second primary cancer is defined as one with a disease-free interval of < 5 years before registration/randomization.

7. Inability to undergo CT or MRI.

8. Current participation in any other interventional clinical trial.

9. Male patients not willing to use adequate contraception or female patients of childbearing potential not willing to use an effective form of contraception such as hormonal birth control, intrauterine device or double barrier method during PCI treatment and subsequent chemotherapy and for at least 6 months thereafter.

10. Breast feeding women or women with a positive pregnancy test at baseline.

11. 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 (transfusion allowed).

12. Inadequate liver function, defined as:

• Serum (total) bilirubin > 2.5 x the Upper Limit of Normal (ULN) for the institution.

• Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3.0 x ULN (> 5 x ULN if liver metastases are present)

• Alkaline phosphatase (ALP) levels > 5.0 x ULN.

13. Inadequate renal function, defined as:

Creatinine clearance < 60 mL/min

14. Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment.

15. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment.

16. Clinically significant and uncontrolled cardiac disease including unstable angina, acute myocardial infarction within six months prior to baseline, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation.

17. Known allergy or sensitivity to photosensitisers.

18. Ataxia telangiectasia.

19. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the planned PCI treatment, affect patient compliance or place the patient at high risk from treatment-related complications.

20. Significant hearing impairment.

21. Patients concurrently receiving phenytoin.

22. Patients defined as vulnerable according to French law (France only)

23. Patients using or have been using photosensitising drugs within the last 7 days (France only)

24. Patients who have received amiodarone in the last year (France only)