Gastrointestinal Stromal Tumor
Conditions
Keywords
GIST
Brief summary
The study is a prospective single armed, open label phase I study. Patients with advanced or metastatic GIST and tumor progression despite ongoing treatment with second, third or fourth line TKI treatment, and with at least one measureable tumor lesion, will be eligible for the study. A maximum of 12 patients will be included in this study. The patients will continue with TKI treatment until the 3 months follow up visit. If further tumor progression TKI will be withdrawn but if stable disease or objective response the patient will continue with TKI until progress. The investigational product Intuvax will be injected into a tumor lesion at two or three treatment occasions; day 1, 14 days (±3 days) after the first vaccination, and 28 days (±3 days) after the second vaccination (patient 7-12 only). Intuvax will be injected in a viable part of the tumor, using ultrasound-guided or CT technique for correct administration.
Interventions
BIOLOGICALIntuvax (ilixadencel)
Therapeutic vaccine: allogeneic, proinflammatory dendritic cells, suspension for intratumoral injection
Sponsors
Mendus
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be informed of the nature of the study and have provided written informed consent. 2. At least 18 years of age. 3. Diagnosis of GIST (according to modified NIH criteria, 2011) where curative excision is no longer an option, i.e. confirmed unresectable or metastatic GIST, and that has progressed on second, third or fourth line tyrosine kinase inhibitor (TKI) treatment. 4. Radiologically measurable tumor(s), i.e at least 3 cm in longest uni-dimensional diameter as measured by CT 5. Clinical and/or CT verified disease progression despite ongoing second, third or fourth line treatment with a TKI 6. Female who has been post-menopausal for more than one (1) year or female of childbearing potential using a highly efficient method of contraception (i.e. a method with less than 1% failure rate \[e.g. sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner with combined use of condom and/or birth control pills\]) during study participation. Female of childbearing potential must have a negative blood pregnancy test at Screening, and if randomized to vaccination a negative blood or urine pregnancy test within one (1) day before each dose of Intuvax, or Male agreeing to use condoms during the study participation or male having a female partner who is using a highly efficient method of contraception as described above during the partner's study participation.
Exclusion criteria
1. Performance status \> ECOG 2 2. Known major reaction/adverse event in connection with previously made vaccination (e.g. asthma, anaphylaxia or other serious reaction) 3. Known major reaction/adverse event in connection with previous transfusions of blood products 4. Active autoimmune disease requiring treatment with systemic immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other rheumatological diseases. 5. Tested positive for HIV 6. Active virus disease (HBV and HCV). 7. Ongoing infection that requires treatment with parenteral antibiotics or antiviral medication 8. Corticosteroid treatment per os exceeding 10mg/day within 7 days prior to the first injection of Intuvax. Inhaled, intranasal and local steroids accepted. 9. Inadequate laboratory parameters, i.e.: * B-Leukocyte count \< 3.0 x109/L * B-Platelet count \< 75 x109/L * B-Hemoglobin \< 100 g/L * P-Prothrombincomplex (PK) \>1.4 * P-APT time outside normal limit 10. Previous organ transplantation 11. Pregnant or lactating women 12. Life expectancy less than 3 months. 13. Investigational treatment (within 28 days) prior to the first injection of Intuvax 14. Known blood dyscrasia (bleeding complication) 15. Prior history of invasive cancer within 5 years before screening, except for adequately treated in situ carcinomas or non melanoma skin cancer 16. History of alcohol or substance abuse 17. patient will not be available for follow up assessments 18. Any other reason that, in the opinion of the investigator, contraindicates that the patient participates in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in vital signs (heart rate, blood pressure, body temperature) | Up to 12 months after vaccination 1 |
| Changes in lab parameters (hematology and biochemistry) during the study versus baseline | Up to 12 months after vaccination 1 |
| Adverse events according to CTCAE v 4.03 | Up to 12 months after vaccination 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival according to mRECIST | Up to 12 months after vaccination 1 | Criteria based on the diameter of the contrast-enhanced portions of the tumor |
| Progression free survival according to RECIST 1.1 | Up to 12 months after vaccination 1 | Criteria based on the maximal tumor diameter |
| Progression free survival according to Choi criteria | Up to 12 months after vaccination 1 | Criteria based on unidimensional tumor size and tumor density on contrast-enhanced CT images. |
| Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to mRECIST | Every 3 months up to 12 months after vaccination 1 | Criteria based on the diameter of the contrast-enhanced portions of the tumor |
| Levels of autoimmunization parameters | Up to 3 months after vaccination 1 | Screening of autoantibodies against nuclear antigens (ANA), including the nuclear antigens SSA, SSB, Sm, RNP, Scl-70, Centromeres and Jo-1 |
| Levels of alloimmunization parameters | Up to 3 months after vaccination 1 | Screening of alloantibodies against HLA-A, B, C (MHC-class I) and HLA-DR (MHC-class II) antigens |
| Changes in WHO-ECOG score | Up to 12 months after vaccination 1 | — |
| Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to RECIST 1.1. | Every 3 months up to 12 months after vaccination 1 | Criteria based on the maximal tumor diameter |
| Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to Choi criteria | Every 3 months up to 12 months after vaccination 1 | Criteria based on unidimensional tumor size and tumor density on contrast-enhanced CT images. |
Countries
Sweden
Outcome results
None listed