Neoadjuvant Tremelimumab and Durvalumab With Gem/Cis in Intrahepatic Cholangiocarcinoma

NCT06017297 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00006462
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Borderline Resectable Carcinoma; Biliary Tract Cancer

Outcome Measures

Primary Outcomes (2)

• Rate of Conversion from unresectable to resectable

  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.

  8 Cycles, 21 day cycles

• Incidence of related treatment emergent adverse events

  Number of participants with related treatment emergent adverse events

  36 months

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  36 months

• Pathological complete response (pCR)

  36 months

• Overall survival (OS)

  36 months

• Progression-free survival (PFS)

  36 months

• Rate of R0 resection

  8 Cycles, 21 day cycles

Study Arms (1)

Durvalumab and Tremelimumab plus gemcitabine/cisplatin

EXPERIMENTAL

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.

Drug: Durvalumab; Drug: Tremelimumab; Drug: Gemcitabine; Drug: Cisplatin; Procedure: Surgical Resection

Interventions

Durvalumab DRUG

Durvalumab 1500 mg via intravenous (IV) infusion every 3 weeks for up to 8 cycles

Durvalumab and Tremelimumab plus gemcitabine/cisplatin

Tremelimumab DRUG

A single dose of tremelimumab at 300mg IV is given on C1.

Durvalumab and Tremelimumab plus gemcitabine/cisplatin

Gemcitabine DRUG

Gemcitabine is dosed at 1000 mg/m2 IV on day (D)1 and D8 of each cycle.

Durvalumab and Tremelimumab plus gemcitabine/cisplatin

Cisplatin DRUG

Cisplatin is dosed at 25mg/m2 on D1 and D8 of each cycle.

Durvalumab and Tremelimumab plus gemcitabine/cisplatin

Surgical Resection PROCEDURE

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.

Durvalumab and Tremelimumab plus gemcitabine/cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of age 18 years and older at the time of study entry, both sexes, all ethnicities.
• Patients with histologically proven intrahepatic cholangiocarcinoma, untreated with systemic therapy.
• Patients with an absence of extrahepatic metastasis (outside of periportal lymph node enlargement) or peritoneal carcinomatosis as demonstrated by CT-scan.
• Patients with a performance status ECOG 0, 1.
• Patients with an estimated life expectancy \> 6 months.
• Patients with disease that is not readily suitable for resection with curative intent, as validated by a multidisciplinary committee with at least one hepatobiliary surgeon, defined as stage II and stage III disease, surgical resectable if there is tumor shrinkage.
• Patients with at least one measurable lesion according to RECIST 1.1 criteria. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to start of study.
• Patients with platelets ≥ 75,000/mm3, polynuclear neutrophils ≥ 1500/mm3, hemoglobin ≥ 9g/dL.
• Patients with serum creatinine \< 1.5 times institutional upper limit of normal (ULN), measured creatinine clearance \> 40 mL/min or Calculated creatinine clearance \> 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24 hour urine collection for determination of creatinine clearance.
• Patients with serum bilirubin ≤ 1.5 times institutional upper limit of normal (ULN) (after biliary drainage if necessary).
• Absolute neutrophil count (ANC ≥ 1.0 × 109 /L)
• Aspartate aminotransferase (AST or SGOT) / alanine transaminase (ALT or SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Patients with a reference CT Scan within 30 days preceding the 1st cycle of treatment.
• Patients with US health insurance coverage.
• Patients are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.

You may not qualify if:

• Patients with hilar or distal cholangiocarcinoma or those with hepatocholangiocarcinoma.
• Patients who are eligible for surgical resection or liver transplantation based on tumor characteristics.
• Patients who would not be surgical candidates due to reasons unrelated to their cholangiocarcinoma, e.g. Cirrhosis with portal hypertension
• Patients with extrahepatic metastases beyond periportal lymph node enlargement
• Patients with a contraindication or grade 3-4 allergy to durvalumab, tremelimumab, gemcitabine, cisplatin, or capecitabine.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of Investigational Product (IP). Note: Local surgery of isolated lesions for palliative intent is acceptable
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone

Sponsors & Collaborators

• Georgetown University: lead
• AstraZeneca: collaborator

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

durvalumab; tremelimumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Aiwu R He, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: August 30, 2023
• Study Start: December 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share