A Phase I/II Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)
National Cancer Institute (NCI)
Summary
Background: Biliary tract carcinoma (BTC) is cancer of the slender tubes that carry fluids in the liver. People with advanced BTC have few treatment options, and their survival rates are very low. Objective: To test a study drug (CDX-1140) combined 3 other drugs (capecitabine, oxaliplatin, Keytruda) in people with BTC. Eligibility: Adults aged 18 years or older with BTC that progressed after treatment and is not eligible for surgery or liver transplant. Design: Participants will be screened. They will have a physical exam. They will have blood tests and tests of their heart function. They will have imaging scans. They may need to have a biopsy: A small sample of tissue will be taken from their tumor using a small needle. Three of the drugs are given through a tube attached to a needle inserted into a vein in the arm (intravenous). The fourth drug is a pill taken by mouth with water. Participants will be treated in 21-day cycles. They will receive intravenous treatments on day 1 and day 8 of the first 6 cycles. After that, they will receive intravenous treatments only on day 1 of each cycle. Participants will take the pill twice a day only for the first 2 weeks of each cycle. They will stop taking this drug after 6 cycles. Imaging scans will be repeated every 9 weeks. Participants may continue receiving the study treatment for up to 2 years. Follow-up visits, including imaging scans, will continue for 3 more years. These images may be taken at other locations and sent to the researchers.
Description
Background: Advanced biliary tract carcinoma (BTC) has limited treatment options in the second line setting and a dismal prognosis. Capecitabine and oxaliplatin (CAPOX) in combination with Keytruda(R) is a tolerable and potentially effective treatment for individuals with refractory advanced BTC. Programmed cell death protein 1 (PD-1) is an inhibitory receptor that is expressed by all Tcells during activation. It regulates T-cell effector functions during various physiological responses, including acute and chronic infection, cancer and autoimmunity, and immune homeostasis. Keytruda(R) is…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: 1. Participants must have histopathological confirmation of BTC or histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC. 2. The maximum tumor size of any individual tumor or metastasis must be \<= 8 cm. 3. Participants should have progressed on standard of care first line systemic treatment or refused standard treatment. 4. Participants must have a disease that is not amenable to potentially curative resection or liver transplantation…
Interventions
- Drugoxaliplatin
Oxaliplatin (130 mg/m2) will be administered IV on Day 1 of each cycle, every 21 days (up to 6 cycles).
- Drugcapecitabine
Capecitabine (750 mg/m2 every 12 hours) will be administered orally with an intermittent schedule: 2 weeks on, 1 week off, of each cycle, every 21 days (up to 6 cycles).
- BiologicalKeytruda
Pembrolizumab (200 mg) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).
- BiologicalCDX-1140
CDX-1140 (0.36-1.5 mg/kg; per assigned dose level) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).
Location
- National Institutes of Health Clinical CenterBethesda, Maryland