PT-112 in Subjects With Thymoma and Thymic Carcinoma
- Conditions
- Thymic Epithelial TumorRecurrent ThymomaThymic Cancer
- Interventions
- Registration Number
- NCT05104736
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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.
- Detailed Description
Background
Platinum-based chemotherapy is the standard of care for advanced unresectable thymic epithelial tumors (TETs). However, more than half of these participants experience disease recurrence and require second-line therapy.
There are no approved drugs for treatment of recurrent thymoma and thymic carcinoma and new therapeutic options are needed for participants who have disease progression on or after platinum-containing therapy.
PT-112, a first-in-class metallo-pyrophosphate conjugate, offers a unique set of properties of both cellular interaction and molecular antitumor mechanisms, including resistance to DNA repair pathways and induction of immunogenic cell death.
PT-112 has been clinically proven to be safe and tolerable and has demonstrated efficacy.
Primary Objectives
To determine the objective response rate (ORR) based on RECIST criteria v1.1 to PT-112 in participants with relapsed or refractory TETs
Eligibility
Participants \>= age 18 years with histologically confirmed, unresectable thymoma or thymic carcinoma who have previously been treated with at least one platinum-containing chemotherapy regimen or must have refused cytotoxic chemotherapy.
Participants must have progressive and measurable disease
Adequate renal, hepatic and hematopoietic function
Design
This will be a single-arm, open-label study with two cohorts (cohort 1: thymoma; cohort 2: thymic carcinoma) to determine the clinical activity and safety of PT-112 in participants with relapsed or refractory TETs.
PT-112 will be administered intravenously at a dose of 360 mg/m\^2 on days 1 and 15 of cycle 1, and at 250 mg/m\^2 on day 1 of each subsequent cycle, until disease progression or development of intolerable adverse events. Each cycle is 28 days.
For participants who develop intolerable toxicity at a dose of 360 mg/m\^2, dose reduction will be permitted to 300 mg/m\^2 after resolution of adverse events to \<= grade 1 or baseline. For participants who develop intolerable toxicity at a dose of 250 mg/m\^2, up to two dose reductions will be permitted to 200 mg/m\^2 or 150 mg/m\^2 after resolution of adverse events to \<= grade 1 or baseline.
Toxicity will be assessed every cycle by CTCAE, version 5.0.
Tumor response will be assessed after completion of every other cycle (8 weeks) using RECIST criteria, version 1.1. Additionally, for participants with pleural dissemination tumor response will be assessed using International Thymic Malignancy Interest Group (ITMIG) modified RECIST criteria.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 53
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PT-112 PT-112 PT-112 will be administered intravenously in 28-day cycles, on Days 1 and 15 at a dose of 360 mg/m2 for cycle 1, and on day 1 at 250mg/m2 for each subsequent cycle, until disease progression, development of intolerable adverse events, or until 8 years after an individual participant has been on study
- Primary Outcome Measures
Name Time Method overall response rate (ORR) assessed every 8 weeks while on treatment and then every 3 months after that for a maximum of 8 years from the start of study best overall response is the best response recorded per RECIST 1.1 criteria, from the start of the treatment until disease progression/recurrence
- Secondary Outcome Measures
Name Time Method overall response rate (ORR) based on ITMIG modified RECIST (ITMIG) start of the treatment until disease progression/recurrence for a maximum of 8 years from the start of study best overall response is the best response recorded per ITMIG modified RECIST criteria
overall survival (OS) during treatment and then every 3 months for a maximum of 8 years from the start of study time from the date of start of treatment until death from any cause
duration of response (DOR) assessed every 8 weeks while on treatment and then every 3 months for a maximum of 8 years from the start of study time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
progression-free survival (PFS) assessed every 8 weeks while on treatment and then every 3 months for a maximum of 8 years from the start of study time from date of start of treatment until time of disease relapse, disease progression, or death
safety of PT-112 safety data routinely collected from initiation of study therapy through long term follow up type, frequency, and grade of events will be collected and reported as assessed per CTCAE criteria, version 5
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States