A Phase II, Open-Label Trial of PT-112 in Subjects With Thymoma and Thymic Carcinoma
Background: There are no approved drugs to treat recurrent thymoma and thymic carcinoma. New therapies are needed for people with these cancers. Researchers want to see if the drug PT-112 can help. PT-112 kills cancer cells. It also helps the body s immune system fight cancer.
Objective: To see if the study drug PT-112 can cause tumors to shrink.
Eligibility: People ages 18 and older who have thymoma or thymic cancer and whose disease returned or progressed after treatment with at least one platinum-containing chemotherapy, or who have refused standard treatment.
Design: Participants will be screened with: Review of medical history and medications Physical exam Blood and urine tests CT or MRI scans of parts of the body, including the brain Participants will get PT-112 in 28-day cycles, on days 1 and 15 of of the first cycle and on day 1 of each cycle after that. They will get the drug by infusion through a catheter. The catheter is a small plastic tube put into a vein. On days they receive the drug, participants will have physical exams and blood and urine tests. They will have an ECG to test heart function on day 1 of each cycle. Participants will have scans every 8 weeks. Participants may choose to have tumor biopsies on day 1 of cycles 1 and 3. Biopsies may be guided by an ultrasound or CT scan. Participants will continue treatment as long as they can handle the side effects and their disease does not get worse, for up to 8 years. Participants will have follow-up visits 2 weeks and 4 weeks after they stop therapy. Then the study team will check on participants every 3 months until 8 years after the participant joined the study.
• Participants must have histologically confirmed thymoma or thymic carcinoma.
• Participants should have received at least one prior line of platinum-based chemotherapy. For participants who have refused cytotoxic chemotherapy, a rationale for refusal to receive standard first-line therapy will be captured in the case report form and the medical record. Progressive disease must be documented prior to study entry and participants must have advanced, unresectable disease that is not amenable to surgical resection.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Participants must be aged \>=18 years.
• ECOG performance status \<=1.
• Participants must have adequate organ and marrow function as defined below:
‣ absolute neutrophil count \>= 1,500/mm3 OR \>= 1.5 x 10(9)/L
⁃ platelets \>=100,000/mm3 OR (Bullet) 100 x 10(9)/L
⁃ hemoglobin \>= 9g/dL (may have been transfused, at least 7 days prior)
⁃ total bilirubin \<= 1.5 x the upper limit of normal range (ULN)
⁃ AST(SGOT)/ALT(SGPT) \<= 2.5 x ULN OR \<= 5 x ULN for participants with documented metastatic disease to the liver
⁃ creatinine \<= 1.5x ULN OR:
⁃ creatinine clearance \>= 60 mL/min/1.73 m2 calculated by calculated using eGRF in the clinical lab
• Negative serum or urine pregnancy test at screening for individuals of childbearing potential (IOCBP). NOTE: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. Absence of pregnancy must be demonstrated unless there is proven menopause (age \>= 50 years and last menarche \>= 3 years, or documented menopausal sex hormone profile, or surgical castration) at screening.
• Participants must not become pregnant or start breast feeding during the study. Breastfeeding should be discontinued if the mother is treated with PT-112.
• Individuals of child-bearing potential and those that can father children with a sexual partner of childbearing potential must use medically effective contraception during the study and for 6 months after the last dose of study medication.
• Participants with previously treated brain or CNS metastases are eligible provided that the participant has recovered from any acute side effects of radiotherapy and does not require treatment with steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to initiation of study therapy.
• Ability of participant to understand and the willingness to sign a written informed consent document.