A phase I study of the safety and immune effects of an escalating dose of autologous GD2 chimeric antigen receptor-expressing peripheral blood T cells in patients with GD2-positive metastatic melanoma and refractory solid tumours

Royal Adelaide Hospital Cancer Centre0 sites12 target enrollmentFebruary 19, 2013

ConditionsMetastatic melanoma Refractory solid tumours Cancer - Malignant melanoma

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Metastatic melanoma
Sponsor: Royal Adelaide Hospital Cancer Centre
Enrollment: 12
Status: Active, not recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

February 19, 2013

End Date

TBD

Last Updated

3 years ago

Study Type

Interventional

Sex

All

Investigators

Sponsor

Royal Adelaide Hospital Cancer Centre

Eligibility Criteria

Inclusion Criteria

•1\.At least 18 years old;
•2\.Histological diagnosis of small cell lung cancer, triple negative breast cancer, osteosarcoma, Ewing sarcoma, and such soft tissue sarcomas as rhabdomyosarcoma, liposarcoma, fibrosarcoma, synovial sarcoma, pleomorphic undifferentiated sarcoma, and desmoplastic small round cell tumours (DSRCT), or metastatic melanoma (surgically incurable and unresectable stage III or stage IV; AJCC Cancer Staging Manual, 7th edition, 2010\) and greater than or equal to 10% GD2 positive cells (by an independent pathologist);
•3\.Unresectable stage III melanoma must have confirmation from a surgical oncologist. Melanoma will have V600 BRAF gene mutation status determined; V600E, K, R, or D mutations may be eligible for treatment with dabrafenib and trametinib;
•4\.Must have failed standard therapy;
•5\.For metastatic melanoma patients, who will not receive dabrafenib and trametinib concurrently with the GD2\-iCAR\-PBT infusion, standard therapy includes prior use of BRAF and/or MEK inhibitor for PBS\-eligible BRAF\-mutant melanoma, combination ipilimumab/nivolumab immunotherapy or pembrolizumab or nivolumab monotherapy. Patients who have not previously tolerated dabrafenib and/or trametinib in the adjuvant or metastatic setting are also eligible. Patients in whom re\-induction with ipilimumab or pembrolizumab or nivolumab is contra\-indicated because of grade 3 or 4 non\-endocrine immune\-related adverse events are also eligible;
•6\.Measurable disease by RECIST 1\.1;
•7\.Must be able and willing to provide written informed consent;
•8\.Eastern Cooperative Oncology Group Performance Status of 0 or 1;
•9\.Recovered to \= Grade 1 from the acute toxic effects of all prior anti\-cancer treatment at least a week before entering this study; for prior ipilimumab, nivolumab, or pembrolizumab, the GD2\-iCAR\-PBT infusion is given 5 half\-lives or greater than or equal to 70 days, greater than or equal to 133 days, or greater than or equal to 110 days after the last dose, respectively;
•10\.Life expectancy of greater than or equal to 12 weeks;

Exclusion Criteria

•1\.Evidence of symptomatic CNS lesions as determined by investigator, use of steroids or anti\-seizure medications for treatment of brain metastases. Patients with asymptomatic lesions previously irradiated or surgically resected that are radiologically stable are eligible. Patients with incidentally found brain metastasis that are asymptomatic and for which no treatment is planned are also eligible;
•2\.Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count less than or equal to 1\.5 x 109/L or platelet count less than or equal to 100 x 109/L (can not be post\-transfusion) or hemoglobin less than 90 g/L (can be post\-transfusion);
•3\.Serum bilirubin \> 1\.5 times the upper limit of normal;
•4\.In absence of metastases, liver transaminase levels \> 2\.5 times the upper limit of normal;
•5\.If metastases are evident, liver transaminase levels \> 5 times the upper limit of normal will be acceptable;
•6\.Creatinine clearance of less than or equal to 50mL/min calculated by Cockcroft\-Gault;
•7\.Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. Patients must be able to swallow tablets;
•8\.Evidence of severe or uncontrolled systemic diseases (e.g., infection requiring treatment with intravenous (IV) antibiotics, unstable or uncompensated respiratory, cardiac \[including life threatening arrhythmias], hepatic, or renal disease.
•9\.Unresolved toxicity greater than or equal to CTC Grade 2 from previous anti\-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor;
•10\.Presence of at least grade 2 peripheral neuropathy;