💬In plain words
What the trial is, and whether it could suit you
This is a First-In-Human trial investigating a novel expansion protocol of an ATIMP (CC-38), composed of autologous TIL.
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* Patient (female or male) has signed informed consent according to ICH/GCP and national/local regulations prior to any trial-specific procedure.
* Patient is 18 years or older at the time of signing the informed consent form.
* Patient must live in an area where a hospital for care can be reached within a maximum of 50 km.
* Patient has histological or cytological confirmation of:
* colorectal cancer, which is stage IV (any T / any N / M1), not amenable to curative surgery, OR
* prostate cancer, which is stage III locally advanced, not amenable to curative surgery (T3-4 / N0 / M0 or any T / N1 / M0), or stage IV metastatic (any T / any N / M1)
* Patient has received all lines of therapy that
* are considered SOC for the patient's indication according to applicable European/national professional society medical guidelines and local medical practice at time of enrollment
* are available via the national health insurance system and the patient is considered eligible for but led to insufficient response or were medically not justified or refused by the patient.
* Patient has confirmed disease progression by radiologic imaging from the previous line of therapy.
* Patient has sufficient amount of previously not irradiated tumor tissue in adequate quality for TIL harvest and expansion, i.e., either:
* Primary or metastatic lesion has been selected for surgery (e.g., to reduce tumor burden, pain relief), Or
* Patient has consented to surgery for the purpose of tissue harvesting for TIL expansion and is considered suitable to undergo surgery for this purpose. Note: Patients with a non-justifiable anesthesiologic and/or surgical risk, as determined by the investigator, should be excluded
* Patient has a least one measurable or assessable lesion according to RECIST 1.1 remaining after tumor resection for CC-38 manufacturing has been performed.
* Patient has ECOG performance status of 0 or 1.
* Patient has a minimum life expectancy of 6 months in the opinion of the investigator from the time of consent date.
* Patient has adequate bone marrow, hepatic and renal function in the opinion of the investigator:
1. Hemoglobin ≥ 9.0 g/dL,
2. Absolute neutrophil count (ANC) ≥ 1.0 x 109 /L,
3. Platelets ≥ 80 x 109 /L,
4. Calculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula),
5. Serum bilirubin ≤ 1.5 x ULN (or ≤ 2.5 x ULN in the presence of documented Gilbert's Syndrome \[unconjugated hyperbilirubinemia\] or liver metastases),
6. AST/ ALT and alkaline phosphatase ≤ 2.5 x ULN (or ≤5 times ULN in the presence of bone and/or liver metastases), ALP ≤ 2.5 x ULN,
7. International normalized ration (INR) ≤ 1.5 or prothrombin time (PT) ≤ ULN + 4 seconds.
* Female patients must be post-menopausal or use contraceptive methods with a failure rate of \< 1% 6 months after last administration of CC-38, whatever is later, to prevent pregnancy. Male patients with fertile female partners must be willing to use condoms with spermicide, and the fertile partner must use contraceptive methods with a failure rate of \< 1% for the same time period. Male patients must also refrain from donating sperm for the same time period.
* Successful tumor tissue sampling by surgery, including presence of TILs in the tumor tissue in the pathological evaluation.
* Successful TIL expansion defined as obtaining the final CC-38 drug product
Exclusion Criteria:
* Patient as any of the following condition:
1. Congestive heart failure NYHA class III or IV,
2. myocardial infarction or coronary artery bypass graft within 6 months prior to enrollment,
3. history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration,
4. history of severe non-ischemic cardiomyopathy,
5. uncontrolled blood pressure as defined as systolic \> 160 mmHg, diastolic \> 100 mmHg within 3 months prior to enrollment,
6. left ventricular ejection fraction (LVEF) \< 45% as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan,
7. any other clinically significant cardiovascular events such as unstable angina, angioplasty, stroke, or transient ischemic attack (TIA) within less than 6 months before enrolment,
8. other conditions that the treating physicians believe may endanger the health of the patients by their participation in this clinical trial.
* Patient has any of the following pulmonary conditions:
1. Forced expiratory volume in 1 second (FEV1)\<60%,
2. Active obstructive chronic pulmonary disease,
3. oxygen dependence as defined by a blood oxygen saturation that can only be maintained above 92% by oxygen inhalation (finger oxygen detection method),
4. other pulmonary conditions that increase the anesthesiologic risk.
* Patient has a current or history of central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression,
* Patient has ulcers in the upper GI tract, untreated or incompletely treated esophageal varices with high risk of bleeding in the investigator's discretion.
* Patient requiring therapeutic anticoagulant therapy or having other increased risk of bleeding events.
* Patient has any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of trial results in the opinion of the investigator.
* Patient has any form of primary immunodeficiency (such as severe combined immunodeficiency disease \[SCID\] and acquired immune deficiency syndrome \[AIDS\]).
* Patient has active or history of autoimmune or inflammatory disorders. Note: Patients may be eligible if they have been assessed in discussion between Principal Investigator, Chief Medical Officer and Senior Medical Consultant as not posing an increased risk to the patient.
* Patient receiving immunosuppressive concomitant medications (≥ 10 mg prednisone daily or other equivalent). Steroid medications are allowed if they are used as substituti