Non-small Cell Lung Cancer, Prostate Cancer, Renal Cancer, Transitional Cell Carcinoma
Conditions
Brief summary
This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug GEM3PSCA in patients with prostate stem cell antigen (PSCA) expressing cancer types which failed to respond to standard therapy.
Interventions
DRUGGEM3PSCA
Infusion of GEM3PSCA, administered intravenously, continuously over 7 days, 2 cycles
Sponsors
GCP-Service International Ltd. & Co. KG
AvenCell Europe GmbH
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation scheme; Single patient cohorts on the first three dose levels, 3+3 afterwards.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, ≥ 18 years of age 2. Progressive PSCA positive cancer (urogenital tract (renal, transitional cell, prostate), non-small cell lung) refractory to standard treatments and with no other available standard or curative treatment 3. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 5. Life expectancy of at least 2 months 6. Platelets \> 50,000/µl 7. Hemoglobin \> 9 g/dl 8. Adequate renal and hepatic laboratory assessments 9. Adequate pulmonary function with oxygen saturation (SpO2) ≥ 90 % and no structural pulmonary disease which might jeopardize patient safety according to judgement of the investigator 10. Left ventricular ejection fraction (LVEF) of ≥ 45 % 11. Existing port-system or central venous catheter resp. acceptance of implantation of a device 12. A female of childbearing potential may be enrolled providing she has a negative pregnancy test at screening visit and is routinely using a highly effective method of birth control resulting in a low failure rate (e.g. hormonal contraception, intrauterine device, total sexual abstinence or sterilization) until 3 months from the last study drug administration. Male patients must also practice a highly effective method of birth Control 13. Able to give written informed consent
Exclusion criteria
1. Other malignancy requiring active therapy 2. Non-measurable tumor disease 3. Patients with active brain metastases (patients with brain metastases or residue after resection with stable size for 6 months in MRI not older than 8 weeks, after consultation with the sponsor, are not excluded from the trial) 4. Use of chemotherapy and radiotherapy within 2 weeks prior to start of trial medication 5. Use of checkpoint inhibitors (having a marketing authorization) within a washout of 5 x t1/2 (half-life); patients with experimental checkpoint inhibitors at all 6. Other investigational drug within the past 4 weeks before start of trial medication 7. Patients undergoing renal dialysis 8. Pulmonary disease with clinical relevant hypoxia 9. Evidence of active, non-infectious pneumonitis or history of interstitial lung disease 10. Cardiac disease: i.e. heart failure NYHA (New York Heart Association) III or IV, unstable coronary artery disease 11. Active central nervous disease (e.g. Parkinson, multiple sclerosis, seizures) and stroke within last 6 months 12. Active gastrointestinal ulceration or bleeding within the last 6 months unless related to underlying malignant disease 13. Renal outflow obstruction, macroscopic or significant microscopic hematuria 14. Active infectious diseases considered by investigator to be incompatible with protocol 15. Major surgery within 28 days 16. Autoimmune diseases requiring steroids at a dose above 10 mg prednisolone equivalent or other immunosuppressants 17. Pregnant or breastfeeding women 18. Psychiatric disorders, drug and/or alcohol abuse 19. Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) 20. Known hypersensitivity to GEM3PSCA excipients 21. Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance) 22. Incapability of understanding purpose and possible consequences of the trial 23. Patients who should not be included according to the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | End of Treatment (EOT) +14 days (DLT period) | MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects. |
| Incidence and intensity of adverse events | End of Treatment (EOT) +14 days (DLT period) | graded according to CTCAE V4.03 |
| Incidence of Dose limiting toxicity (DLT) | End of Treatment (EOT) +14 days (DLT period) | Dose Limiting Toxicity is defined as any event at least possibly related to investigational medicinal product (IMP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase 2 dose (RP2D) | From start of treatment until up to 14 days after last treatment cycle (2 initial cycles + max. 6 additional cycles per patient). Each cycle consists of 7 days treatment plus DLT evaluation period (14 days) | The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles. |
| Antitumor activity of GEM3PSCA according to RECIST1.1 (Response Evaluation Criteria in Solid Tumors) | End of Treatment (EOT) +14 days (DLT period) | response rates |
| Prostate specific antigen (PSA) response in patients with prostate cancer | End of Treatment (EOT) +14 days (DLT period) | — |
| Overall survival (OS) | End of Treatment (EOT) + 14 days (DLT period) | — |
| Influence on circulating tumor cells in patients with prostate cancer | Day 8 / End of Treatment (EOT) | — |
Countries
Germany
Outcome results
None listed