Malignant Solid Tumour
Conditions
Keywords
Phase I, Dose escalation, oncolytic virus
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.
Interventions
GENETICONCOS-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.
Sponsors
Targovax Oy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any (Serious and Non-Serious) Adverse Event Measured to Assess Safety and Tolerability. | 6 months | — |
| Recommended Phase 2 Dose by Identification of Any Dose Limiting Toxicities | 6 months | No Dose Limiting Toxicities were observed at any dose level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Safety, Tolerability and Adverse Event Profile of CGTG-102 With Low-dose CPO. To Obtain Preliminary Evidence of Antitumour Activity. | 12 months | Clinical and laboratory assessment. Response rate, disease control rate, progression free and overall survival. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Infiltration of CD8+ T Cells Into Tumors. | 6 months | — |
| 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. | 3 months | — |
| Number of Patients With Induction of Tumor-specific CD8+ T Cells in Peripheral Blood Monomuclear Cells. | 6 months | — |
| Quality of Life Using EORTC QLQ-C30. | 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. | 6 hours | — |
Countries
Finland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CGTG-102 CGTG-102 dose escalation
CGTG-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. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Deterioration of WHO status to WHO 4 | 2 |
| Overall Study | Disease progression | 6 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | CGTG-102 |
|---|---|
| Age, Continuous | 63 years |
| Number of cancer indications | 9 participants |
| Region of Enrollment Finland | 12 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 5 / 12 |
Outcome results
Primary
Number of Participants With Any (Serious and Non-Serious) Adverse Event Measured to Assess Safety and Tolerability.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGTG-102 | Number of Participants With Any (Serious and Non-Serious) Adverse Event Measured to Assess Safety and Tolerability. | 12 participants |
Primary
Recommended Phase 2 Dose by Identification of Any Dose Limiting Toxicities
No Dose Limiting Toxicities were observed at any dose level.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGTG-102 | Recommended Phase 2 Dose by Identification of Any Dose Limiting Toxicities | 0 Dose limiting toxicities |
Secondary
To Determine the Safety, Tolerability and Adverse Event Profile of CGTG-102 With Low-dose CPO. To Obtain Preliminary Evidence of Antitumour Activity.
Clinical and laboratory assessment. Response rate, disease control rate, progression free and overall survival.
Time frame: 12 months
Other Pre-specified
An Immune Response to Treatment Was Assessed by Measuring a Temporary Increase in Pro-inflammatory Cytokines After Treatment Was Administrered.
Time frame: 6 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGTG-102 | An Immune Response to Treatment Was Assessed by Measuring a Temporary Increase in Pro-inflammatory Cytokines After Treatment Was Administrered. | 12 participants |
Other Pre-specified
Number of Participants With Infiltration of CD8+ T Cells Into Tumors.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGTG-102 | Number of Participants With Infiltration of CD8+ T Cells Into Tumors. | 11 participants |
Other Pre-specified
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGTG-102 | 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. | 4 participants |
Other Pre-specified
Number of Patients With Induction of Tumor-specific CD8+ T Cells in Peripheral Blood Monomuclear Cells.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGTG-102 | Number of Patients With Induction of Tumor-specific CD8+ T Cells in Peripheral Blood Monomuclear Cells. | 2 participants |
Other Pre-specified
Quality of Life Using EORTC QLQ-C30.
To assess the feasibility and usefulness of EORTC QLQ-C30 for possible use in later studies.
Time frame: 12 months