ONCOS-102 (Previously CGTG-102) for Therapy of Advanced Cancers

• ClinicalTrials.gov Identifier: NCT01598129
• Recruitment Status: Completed
• First Posted: May 15, 2012
• Results First Posted: October 2, 2014
• Last Update Posted: October 24, 2016
• Sponsor: Targovax Oy
• Information provided by (Responsible Party): Targovax ASA ( Targovax Oy )

Tracking Information

• First Submitted Date: April 19, 2012
• First Posted Date: May 15, 2012
• Results First Submitted Date: June 11, 2014
• Results First Posted Date: October 2, 2014
• Last Update Posted Date: October 24, 2016
• Study Start Date: April 2012
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 1, 2014)

• Number of Participants With Any (Serious and Non-Serious) Adverse Event Measured to Assess Safety and Tolerability. [ Time Frame: 6 months ]
• Recommended Phase 2 Dose by Identification of Any Dose Limiting Toxicities [ Time Frame: 6 months ]
  No Dose Limiting Toxicities were observed at any dose level.

• Original Primary Outcome Measures (submitted: May 10, 2012): To determine the recommended phase II dose. [ Time Frame: 12 months ]

Current Secondary Outcome Measures (submitted: October 1, 2014)

To Determine the Safety, Tolerability and Adverse Event Profile of CGTG-102 With Low-dose CPO. To Obtain Preliminary Evidence of Antitumour Activity. [ Time Frame: 12 months ]

Clinical and laboratory assessment. Response rate, disease control rate, progression free and overall survival.

Original Secondary Outcome Measures (submitted: May 10, 2012)

• To obtain preliminary evidence of antitumour activity. [ Time Frame: 12 months ]
  Response rate, disease control rate, progression free and overall survival.
• The effect of CGTG-102 on biological correlates: virus replication, cellular and humoral responses [ Time Frame: 12 months ]
• Quality of Life using EORTC QLQ-C30. [ Time Frame: 12 months ]
  To assess the feasibility and usefulness of EORTC QLQ-C30 for possible use in later studies.

Current Other Pre-specified Outcome Measures (submitted: October 1, 2014)

• Number of Participants With Stable Disease Status as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Evaluation Three Months After Starting CGTG-102 Treatment. [ Time Frame: 3 months ]
• Quality of Life Using EORTC QLQ-C30. [ Time Frame: 12 months ]
  To assess the feasibility and usefulness of EORTC QLQ-C30 for possible use in later studies.
• An Immune Response to Treatment Was Assessed by Measuring a Temporary Increase in Pro-inflammatory Cytokines After Treatment Was Administrered. [ Time Frame: 6 hours ]
• Number of Participants With Infiltration of CD8+ T Cells Into Tumors. [ Time Frame: 6 months ]
• Number of Patients With Induction of Tumor-specific CD8+ T Cells in Peripheral Blood Monomuclear Cells. [ Time Frame: 6 months ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ONCOS-102 (Previously CGTG-102) for Therapy of Advanced Cancers
• Official Title: Exploratory Open Label Study of GM-CSF Coding Oncolytic Adenovirus CGTG-102, With Low Dose Cyclophosphamide in Patients With Refractory Injectable Solid Tumours
• Brief 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.

Detailed Description

CGTG-102 is an adenovirus that has been armed with granulocyte-macrophage colony stimulating factor (GMCSF), a potent stimulator of immunological cells.

With regard to oncolytic viruses, replication in normal cells does not take place, and therefore viruses such as CGTG-102 are not known to cause any disease. Further, to date there has been no incidence of passing the virus on to other humans from patients. Since the virus requires tumor cells to multiply, such events are unlikely.

To this day more than 100 patients have been treated with CGTG-102. This clinical trial will take place over approximately 6 months. The study includes 12 visits to the hospital, 1 screening visit, 9 injection visits including overnight stay at the hospital(performed on trial days 1, 4, 8, 15, 29, 57, 85, 113 and 141), 1 end of treatment visit (day 169) and 1 end of study visit (day 190). Oral treatment with cyclophosphamide (1 pill per day) will start on the day after the first injection and last until visit day 169.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Malignant Solid Tumour

Intervention

Genetic: ONCOS-102

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.

Study Arms

Experimental: CGTG-102

CGTG-102 dose escalation

Intervention: Genetic: ONCOS-102

• Publications *: Ranki T, Pesonen S, Hemminki A, Partanen K, Kairemo K, Alanko T, Lundin J, Linder N, Turkki R, Ristimäki A, Jäger E, Karbach J, Wahle C, Kankainen M, Backman C, von Euler M, Haavisto E, Hakonen T, Heiskanen R, Jaderberg M, Juhila J, Priha P, Suoranta L, Vassilev L, Vuolanto A, Joensuu T. Phase I study with ONCOS-102 for the treatment of solid tumors - an evaluation of clinical response and exploratory analyses of immune markers. J Immunother Cancer. 2016 Mar 15;4:17. doi: 10.1186/s40425-016-0121-5. eCollection 2016.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 10, 2012): 12
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 2013
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland

Administrative Information

• NCT Number: NCT01598129
• Other Study ID Numbers: Oncos-C1
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Targovax ASA ( Targovax Oy )
• Study Sponsor: Targovax Oy
• Collaborators: Not Provided

Investigators

• Study Director: Mikael von Euler, MD PhD; Oncos Therapeutics Ltd.

• PRS Account: Targovax ASA
• Verification Date: October 2016