CDX-1140 + CAPOX + Keytruda for Bile Duct Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Maria C Monge Bonilla, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Live vaccines, Immunosuppressants

Disqualifiers: HIV, Pneumonitis, Autoimmune diseases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or other immunosuppressive medications, you may not be eligible to participate.

What data supports the effectiveness of the drug combination CDX-1140 + CAPOX + Keytruda for bile duct cancer?

Research shows that the combination of pembrolizumab (Keytruda) with capecitabine and oxaliplatin (CAPOX) has been studied in patients with advanced biliary tract cancer, showing some clinical efficacy. Additionally, CAPOX alone has been found to be an active treatment option for certain types of advanced biliary cancers, suggesting potential benefits when combined with other therapies like CDX-1140.

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Is the combination of CDX-1140, CAPOX, and Keytruda safe for humans?

The combination of capecitabine and oxaliplatin (CAPOX) has been shown to be generally well-tolerated in patients with advanced biliary system cancers, with the most common serious side effect being peripheral sensory neuropathy (nerve damage causing tingling or numbness).

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What makes the CDX-1140 + CAPOX + Keytruda treatment unique for bile duct cancer?

This treatment is unique because it combines CDX-1140, an experimental drug that stimulates the immune system, with CAPOX (capecitabine and oxaliplatin), a chemotherapy regimen, and Keytruda (pembrolizumab), an immunotherapy drug. This combination aims to enhance the body's immune response against cancer cells, which is different from standard chemotherapy alone.

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Eligibility Criteria

Adults over 18 with advanced Biliary Tract Carcinoma (BTC) that's worsened after treatment and can't be removed by surgery or improved with a liver transplant. They must have acceptable organ function, no recent major surgeries, not be pregnant, and agree to use contraception. People who've had certain vaccines recently, those with HIV or active CNS metastases, or a history of severe allergies to similar drugs are excluded.

Inclusion Criteria

My organs and bone marrow are functioning well.

My largest tumor or metastasis is 8 cm or smaller.

I am breastfeeding but willing to stop during the study.

Exclusion Criteria

I am on long-term steroids or other drugs that weaken my immune system.

I haven't had cancer treatment in the last 4 weeks.

I have previously been treated with anti-CD40 therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive CDX-1140, capecitabine, oxaliplatin, and Keytruda in 21-day cycles. Intravenous treatments are given on day 1 and day 8 for the first 6 cycles, and only on day 1 thereafter. The pill is taken twice a day for the first 2 weeks of each cycle, stopping after 6 cycles.

Up to 2 years

Intravenous treatments on day 1 and day 8 for the first 6 cycles, then only on day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment, with imaging scans repeated every 9 weeks and follow-up visits continuing for 3 more years.

3 years

Imaging scans every 9 weeks

Participant Groups

The trial is testing CDX-1140 in combination with Capecitabine (a pill), Oxaliplatin (intravenous), and Keytruda (intravenous) for BTC treatment. Participants will undergo cycles of these treatments: intravenous on days 1 and 8 for the first six cycles then day 1 only afterward; pills taken twice daily for two weeks each cycle but stopped after six cycles.

Group I: Phase II Experimental Treatment 4 Interventions

Keytruda, oxaliplatin, capecitabine and estimated safe dose of CDX-1140

Group II: Phase I Experimental Treatment 4 Interventions

Keytruda, oxaliplatin, capecitabine and escalating doses of CDX-1140

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

🇺🇸 Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

🇨🇦 Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

🇯🇵 Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

A Phase II Study of Pembrolizumab in Combination with Capecitabine and Oxaliplatin with Molecular Profiling in Patients with Advanced Biliary Tract Carcinoma. [2022] We conducted a phase II study of the combination of pembrolizumab with capecitabine and oxaliplatin (CAPOX) in patients with advanced biliary tract carcinoma (BTC) to assess response rate and clinical efficacy. Exploratory objectives included correlative studies of immune marker expression, tumor evolution, and immune infiltration in response to treatment.

2. England pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. [2022] This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m(-2), day 1) plus capecitabine (1000 mg m(-2) b.i.d., days 1-14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0-15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3-11.7; ECC: 16.8 months; 95% CI, 12.7-20.5), and 5.2 months (95% CI, 0.6-9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3-4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.

3. United States pubmed.ncbi.nlm.nih.gov

Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers. [2023] BACKGROUNDMEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition.METHODSThis open-label phase II study randomized patients with BTC to atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1. The primary endpoint was progression-free survival (PFS).RESULTSSeventy-seven patients were randomized and received study therapy. The trial met its primary endpoint, with a median PFS of 3.65 months in the combination arm versus 1.87 months in the monotherapy arm (HR 0.58, 90% CI 0.35-0.93, 1-tail P = 0.027). One patient in the combination arm (3.3%) and 1 patient in the monotherapy arm (2.8%) had a partial response. Combination therapy was associated with more rash, gastrointestinal events, CPK elevations, and thrombocytopenia. Exploratory analysis of tumor biopsies revealed enhanced expression of antigen processing and presentation genes and an increase in CD8/FoxP3 ratios with combination treatment. Patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells had evidence of greater clinical benefit from the combination.CONCLUSIONThe combination of atezolizumab plus cobimetinib prolonged PFS as compared with atezolizumab monotherapy, but the low response rate in both arms highlights the immune-resistant nature of BTCs.TRIAL REGISTRATIONClinicalTrials.gov NCT03201458.FUNDINGNational Cancer Institute (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN); F. Hoffmann-La Roche, Ltd.; NCI, NIH (R01 CA228414-01 and UM1CA186691); NCI's Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancers (P50 CA062924); NIH Center Core Grant (P30 CA006973); and the Passano Foundation.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Third-Line Palliative Systemic Therapy for Advanced Biliary Tract Cancer: Multicentre Review of Patterns of Care and Outcomes. [2023] Phase 3 trials have established standard first-line (1L) and 2L systemic therapy options for patients with advanced biliary cancer (ABC). However, a standard 3L treatment remains undefined. Clinical practice and outcomes for 3L systemic therapy in patients with ABC were therefore evaluated from three academic centres. Included patients were identified using institutional registries; demographics, staging, treatment history, and clinical outcomes were collected. Kaplan-Meier methods were used to assess progression-free survival (PFS) and overall survival (OS). Ninety-seven patients, treated between 2006 and 2022, were included; 61.9% had intrahepatic cholangiocarcinoma. At the time of analysis, there had been 91 deaths. Median PFS from initiating 3L palliative systemic therapy (mPFS3) was 3.1 months (95%CI 2.0-4.1), while mOS3 was 6.4 months (95%CI 5.5-7.3); mOS1 was 26.9 months (95%CI 23.6-30.2). Among patients with a therapy-targeted molecular aberration (10.3%; n = 10; all received in 3L), mOS3 was significantly improved versus all other included patients (12.5 vs. 5.9 months; p = 0.02). No differences in OS1 were demonstrated between anatomical subtypes. Fourth-line systemic therapy was received by 19.6% of patients (n = 19). This international multicentre analysis documents systemic therapy use in this select patient group, and provides a benchmark of outcomes for future trial design.

5. United States pubmed.ncbi.nlm.nih.gov

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data. [2023] The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting.

6. United States pubmed.ncbi.nlm.nih.gov

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. [2022] To determine the safety and efficacy of capecitabine (Xeloda; Roche Laboratories, Nutley, NJ) in patients with metastatic or unresectable, locally advanced pancreatic cancer.

7. China pubmed.ncbi.nlm.nih.gov

[Preliminary study of XELOX regimen as the first-line chemotherapy in advanced or recurrent gastric cancer]. [2020] To evaluate the efficacy and toxicity of the combined therapy with oxaliplatin and capecitabine (XELOX) in patients with advanced or recurrent gastric cancer.

8. United States pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. [2022] To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer.

9. China pubmed.ncbi.nlm.nih.gov

[Oxaliplatin plus capecitabine as a second line chemotherapy for patients with advanced gastric cancer]. [2018] To evaluate the effect and toxicity of oxaliplatin combined with capecitabine (Xeloda) as a second-line chemotherapy regimen for patients with advanced gastric cancer.

10. Japan pubmed.ncbi.nlm.nih.gov

[CapeOX Therapy as a Salvage Treatment for Advanced Gastric Cancer Refractory to S-1, Cisplatin, Irinotecan, and Taxanes]. [2019] This study aimed to retrospectively evaluate the efficacy and safety of capecitabine plus oxaliplatin(CapeOX)for heavily pretreated advanced gastric cancer(AGC)refractory to S-1, cisplatin, irinotecan, and taxanes.

11. England pubmed.ncbi.nlm.nih.gov

Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. [2020] To determine the efficacy and tolerability of capecitabine combined with oxaliplatin (CAPOX) or irinotecan (CAPIRI) as first-line treatment in patients with advanced/metastatic colorectal cancer aged > or =70 years.

12. Greece pubmed.ncbi.nlm.nih.gov

XELOX vs. FOLFOX4 as second line chemotherapy in advanced pancreatic cancer. [2022] The efficacy and tolerability of oxaliplatin in combination with either folinic acid, fluoro-uracil (5-FU) (FOLFOX4 regimen) or capecitabine (XE-LOX regimen) was evaluated in advanced pancreatic cancer.