Neoadjuvant Tremelimumab and Durvalumab With Gem/Cis in Intrahepatic Cholangiocarcinoma (ESR-22-21719)
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|ClinicalTrials.gov Identifier: NCT06017297|
Recruitment Status : Not yet recruiting
First Posted : August 30, 2023
Last Update Posted : September 18, 2023
The goal of this clinical trial is to test feasibility and safety of the combination of tremelimumab and durvalumab plus gemcitabine and cisplatin as a neoadjuvant treatment bridge patients to a curative resection in treatment naïve borderline resectable, or resectable with high risk for recurrence intrahepatic cholangiocarcinoma patients. The main question[s] it aims to answer are:
- What is the rate of conversion of unresectable tumor to resectable cancer?
- What are the side effects of this treatment combination?
Participants will undergo an initial tumor biopsy, imaging and laboratory studies prior to starting treatment with durvalumab, tremelimumab, gemcitabine and cisplatin. Participants will continue for 4 cycles and if the tumor is found to be resectable then they will undergo surgical resection. If the tumor is unresectable (can't be surgically removed) after 4 cycles, then participants will receive 4 more cycles and repeated imaging. If the tumor remains unresectable then the participant will be treated with capecitabine for up to 8 cycles and durvalumab for up to 12 months.
|Condition or disease||Intervention/treatment||Phase|
|Borderline Resectable Carcinoma Biliary Tract Cancer||Drug: Durvalumab Drug: Tremelimumab Drug: Gemcitabine Drug: Cisplatin Procedure: Surgical Resection||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Neoadjuvant Durvalumab (MEDI4736) and Tremelimumab in Combination With Gemcitabine and Cisplatin in Patients With Intrahepatic Cholangiocarcinoma That is Borderline Resectable/Resectable But With High Risk for Recurrence.|
|Estimated Study Start Date :||November 2023|
|Estimated Primary Completion Date :||November 2026|
|Estimated Study Completion Date :||November 2026|
Experimental: Durvalumab and Tremelimumab plus gemcitabine/cisplatin
Durvalumab and tremelimumab plus gemcitabine/cisplatin combination therapy. If the tumor is evaluated to be resectable after Cycle 4 (C4), then the patient may proceed with surgical tumor resection. If the tumor is deemed unresectable after C4, then the patient will proceed with Cycle 5-8 followed by reevaluation for surgical resection.
Durvalumab 1500 mg via intravenous (IV) infusion every 3 weeks for up to 8 cycles
A single dose of tremelimumab at 300mg IV is given on C1.
Gemcitabine is dosed at 1000 mg/m2 IV on day (D)1 and D8 of each cycle.
Cisplatin is dosed at 25mg/m2 on D1 and D8 of each cycle.
Procedure: Surgical Resection
If the tumor is evaluated to be resectable (as defined as successfully treated stage II (tumor shrink away from vessels), stage IIIA (tumor shrink away from visceral peritoneum), stage IIIB (N1 disease no longer pathologically enlarged) after C4 or C8, then the patient may proceed with surgical tumor resection.
- Rate of Conversion from unresectable to resectable [ Time Frame: 8 Cycles, 21 day cycles ]Rate of conversion of unresectable tumor to resectable cancer after neoadjuvant durvalumab + tremelimumab + gemcitabine + cisplatin after 4 or 8 cycles. Surgical evaluation will be done in joint by institutional radiology and hepatobiliary surgery using clinical data (CT/MRI imaging, patient performance status, labs, etc.) If among the evaluable 24 patients, 9 or more (45%) patients undergo such conversion, the investigational treatment will be considered as promising/feasible. The resectable rate will be estimated with its 95% exact confidence interval.
- Incidence of related treatment emergent adverse events [ Time Frame: 36 months ]Number of participants with related treatment emergent adverse events
- Objective Response Rate (ORR) [ Time Frame: 36 months ]ORR will be estimated with its 95% exact confidence interval based on RECIST v1.1
- Pathological complete response (pCR) [ Time Frame: 36 months ]
- Overall survival (OS) [ Time Frame: 36 months ]Kaplan-Meier method is used to represent secondary outcome OS.
- Progression-free survival (PFS) [ Time Frame: 36 months ]Kaplan-Meier method is used to represent secondary outcome of PFS
- Rate of R0 resection [ Time Frame: 8 Cycles, 21 day cycles ]R0 resection rate will be estimated with its 95% exact confidence interval
- Relapse free survival (RFS) [ Time Frame: 36 months ]Kaplan-Meier method will be used to analyze RFS
- Patient Reported outcomes (PRO) decline [ Time Frame: 8 Cycles, 21 day cycles ]As measured by qualify of life changes per EORTC QLQ-BIL-20 questionnaires. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
- Event Free Survival (EFS) [ Time Frame: 36 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06017297
|Contact: Aiwu He, MDemail@example.com|
|United States, District of Columbia|
|Lombardi Comprehensive Cancer Center, Georgetown University|
|Washington, District of Columbia, United States, 20007|
|Contact: Nicole Swanson 202-687-9194 firstname.lastname@example.org|
|Principal Investigator: Aiwu He, MD|
|Principal Investigator:||Aiwu R He, MD||Georgetown University|