ONCOS-102 (Previously CGTG-102) for Therapy of Advanced Cancers
Condition: Malignant Solid Tumour
Intervention: ONCOS-102
Intervention description: GMCSF encoding 3/5 chimeric adenovirus for intratumoral and intravenous injection on day 1, 4, 8, 15, 29, 57, 85, 113 and 141 tested in three different dose cohorts (3x10E10, 1x10E11 and 3x10E11) in combination with low-dose metronomic cyclophosphamide.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase I; Dose escalation; oncolytic virus

Summary:

      The purpose of the study is to investigate the safety and the recommended dose for later use
      of an oncolytic adenovirus CGTG-102 in combination with low-dose oral cyclophosphamide in the
      treatment of advanced cancers.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Solid tumour refractory to evidence-based oncological therapies.

          2. Age 18 years and over.

          3. At least one tumour mass measurable by PET (i.e. PET-positive lesion that can reliably
             be assessed for SUVmax, typically featuring longest diameter ≥2 cm).

          4. Tumour is injectable i.t. by direct visualisation/palpation or by imaging-guidance
             (ultrasound). I.t. includes intracavitary injections, particularly intraperitoneal and
             intrapleural.

          5. Histological confirmation of primary disease or relapse.

          6. Patient has given signed informed consent.

          7. WHO performance score 0-1 and life expectancy more than 3 months.

          8. Previous anti-cancer treatment at least 1 month before Day 1.

          9. Tumour assessed to be suitable for biopsy.

         10. Hepatic, renal and bone marrow functions within normal limits for the target
             population as indicated by the following:

               -  Total bilirubin ≤ the upper limit of normal (ULN).

               -  ASAT, ALAT ≤3.0 × ULN.

               -  Serum creatinine ≤1.5 x ULN.

               -  International normalised ratio (INR) ≤1.5 x ULN.

               -  Haematologic parameters: Patients can be transfused to meet the haemoglobin and
                  platelet count entry criteria.

                    -  Haemoglobin ≥10 g/dL

                    -  Leucocytes ≥2.3 x 109/L

                    -  Platelet count ≥7.5 x 109/L

        Exclusion Criteria:

          1. Use of high dose systemic immune suppressive medication within 3 weeks of anticipated
             first treatment. Note: patients taking low-dose corticosteroids for the treatment of
             nausea and/or taking maintenance corticosteroids are permitted to enrol.

          2. Known infection with HIV or known underlying genetic immunodeficiency disease as these
             might affect the safety and efficacy of treatment.

          3. Treatment of the injected tumour(s) with radiotherapy, chemotherapy, surgery, or an
             investigational drug within 4 weeks prior to the first treatment.

          4. Recent thromboembolic event (deep venous thrombosis, pulmonary embolism).

          5. Clinically significant active infection or clinically significant medical condition
             considered high risk for investigational new drug treatment (e.g. pulmonary,
             neurological, cardiovascular, metabolic, clinically significant and/or rapidly
             accumulating pericardial effusion).

          6. Severe or unstable cardiac disease.

          7. Known brain metastases, glioma. Central nervous system malignancy, including
             carcinomatosis meningitis.

          8. Pulse oximetry oxygen saturation <90% at rest in room air.

          9. Vaccination with a live virus (i.e. measles, mumps, rubella, etc.) <30 days prior to
             the first treatment.

         10. History of hepatic dysfunction, cirrhosis or hepatitis.

         11. Prior organ transplant.

         12. Pregnant or lactating patients.

         13. Evidence of coagulation disorder.

         14. Other conditions which, in the opinion of the investigator, might interfere with the
             study findings or represent a safety hazard for the patient.