A First-in-Human Phase I Trial With Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors and Carcinomas
Background: Neuroendocrine neoplasms (NENs) are rare cancers in the gastrointestinal tract, pancreas, lungs, adrenal glands, and other areas of the body. Many of these cancers have a high risk of relapse and a low chance of survival. Better treatments are needed.
Objective: To test a new drug, ADCT-701, in people with NENs.
Eligibility: Adults aged 18 and older with NENs.
Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of heart functioning. Their ability to perform normal daily activities will be tested. A biopsy may be needed: A sample of tissue will be removed from the tumor. ADCT-701 is given through a tube attached to a needle inserted into a vein in the arm. Participants will receive the drug treatment on the first day of 21-day treatment cycles. They will visit the clinic a total of 10 times during the first two cycles. After that, they will visit the clinic 2 times during each cycle. Imaging scans, blood draws, heart function tests, and other tests will be repeated during study visits. Each visit will last up to 8 hours. Participants may continue receiving treatment with the study drug for up to 2 years. After treatment ends, participants will have follow-up clinic visits 4 times in 4 months. They will have a physical exam, with heart and blood tests, at each visit. After that, they will have follow-up clinic visits every 9 weeks; these visits will include imaging scans. Follow-up visits will continue for up to 5 years after treatment began....
• Participants must have histologically or cytologically confirmed neuroendocrine neoplasms or malignant adrenocortical carcinoma (ACC).
• Locally advanced or metastatic disease (as confirmed by a radiological evaluation).
• Participants must have measurable disease per RECIST 1.1.
• Participants must have received prior standard of care treatment and be refractory to or intolerant to standard of care therapy(s).
• Age \>= 18 years.
• ECOG performance status \<= 2.
• Adequate hematologic function as follows:
‣ Leukocytes \>= 3,000/microliter
⁃ Absolute neutrophil count (ANC) \>= 1,200/microliter (off-growth factors for 72 hours prior to treatment initiation)
⁃ Hemoglobin (Hgb) \>= 9 g/dL with no blood transfusion within 2 weeks prior to treatment initiation
⁃ Platelets \>= 100,000/microliter with no platelet transfusion within 1 week.
• Adequate renal and hepatic function as follows:
‣ Creatinine clearance (CrCl) \>= 50 mL/min/1.73 m\^2 (calculated CrCl (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or calculated eGFR provided by a laboratory))
⁃ Total bilirubin \<= 1.5 x ULN OR in participants with known or suspected Gilbert's syndrome, total bilirubin \<= 3.0 x ULN
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 2.5 x ULN, (unless liver metastases are present, then values must be \<= 5 x ULN).
• Participants serologically positive for hepatitis C virus (HCV) must have an undetectable HCV viral load.
• Participants serologically positive for Hepatitis B (HBV) core antibody or surface antigen must be on adequate anti-viral therapy and Hepatitis B Viral deoxyribonucleic acid (DNA) load must be \<2000 IU/mL.
• Participants serologically positive for human immunodeficiency virus (HIV) must be on stable antiretroviral therapy for at least 4 weeks before treatment initiation, have no reported opportunistic infections or Castleman s disease within 12 months prior to treatment initiation, have a viral load that is undetectable by quantitative polymerase chain reaction (PCR) and CD4 count \>= 200 cells per cubic millimeter.
• Participants with brain metastasis are eligible if at least 4 weeks status post radiotherapy or surgery before treatment initiation with no evidence of progression or associated symptoms.
• Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization) for the duration of the study treatment and up to 9.5 months after the last dose of the ADCT-701 (restriction period).
∙ Individuals who can father children must agree to use an effective method of contraception (barrier, surgical sterilization) at study entry and up to 6.5 months after the last dose of the ADCT-701.
• Nursing participants must be willing to discontinue nursing from study treatment initiation through 6.5 months after study treatment discontinuation.
• Participants must be able to understand and be willing to sign a written informed consent document.