Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig in Resectable iCCA

NCT06569225 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 24-5716
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Biliary tract cancer is a highly aggressive and heterogeneous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (CCA), or the gallbladder (GBC)(1-3). While it accounts for only 0.7% of all malignant tumors and 3% of all gastrointestinal malignancies in adults, both incidence and mortality are increasing. Biliary tract cancers usually present at an advanced stage, with only approximately 20% of patients being diagnosed with an early-stage disease (1, 2, 4). There is a high risk of recurrence post curative radical resection, with 60-70% of patients recurring within 5 years, with 5-year survival of around 25% (1, 2, 5). There is evidence for use of adjuvant chemotherapy with fluoropyrimidine- based regimens as per the BILCAP and ASCOT phase III trials \[(5-7).However, despite advances in adjuvant treatment, recurrence rates after resection of BTC remain high even with adjuvant chemotherapy. For example, in the BILCAP study, 5-year RFS was reported as 33.9% (95% CI: 27.6 to 40.2) (1). Therefore, an unmet need exists to optimize peri-operative treatment to reduce recurrence and improve outcomes in patients with resectable BTC.

Conditions

Cholangiocarcinoma Resectable

Keywords

CCA; Biliary cancer; Neo-adjuvant and adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Major pathological response (MPR), defined as >70% tumor necrosis

  To determine pathological response rate to neoadjuvant Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig in resected tumour

  2 years

Secondary Outcomes (4)

• Objective response rate (ORR)

  3 years

• The number of patients who experience a surgical delay and/or drop off due to treatment related adverse events (TRAEs) or progressive disease

  2 years

• The number of ≥ grade 3 adverse events (AEs) or immune related adverse events that occur during treatment

  3 years

• Rate of R0

  2 years

Study Arms (1)

Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig

EXPERIMENTAL

Drug: Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig

Interventions

Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig DRUG

: Patients will receive prior to surgery: 2 cycles of combinational therapy with Gemcitabine (800mg) /Cisplatin (25mg) /Nab-Paclitaxel (100mg) and Rilvegostomig (Q3W). Post-surgical resection, adjuvant therapy will consist of 4 cycles of Gemcitabine (1000mg) /Cisplatin (25mg) and Rilvegostomig (Q3W). Rilvegostomig (Q3W) will be continued for a total of 12 months in the adjuvant phase

Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig

Eligibility Criteria

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

You may qualify if:

• Patient must be capable of providing written informed consent.
• Age \>18 years at time of study entry
• Histologically proven intrahepatic cholangiocarcinoma
• Complete surgical resection of the tumor must be achievable\*. Resection should include a portal lymphadenectomy as per standard of care.
• No prior cytotoxic, targeted or immune therapy
• Have provided archival tumor tissue sample or preferably freshly obtained biopsy of a tumor lesion not previously irradiated for mandatory pre-treatment evaluation (baseline).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Estimated life expectancy \>3 months
• If underlying liver cirrhosis, Childs Pugh score of 5 or 6
• If underlying liver disease, ALBI grade ≤2†
• Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (HBV DNA ≤2000 IU/mL) prior to study entry. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\<10 IU/ml or under limit of detection per local lab standard) do not require anti-viral therapy prior to study entry. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
• Patients with HCV infection must have management of this disease per local institutional practice throughout the study. HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrollment.
• Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients.
• Adequate normal organ and marrow function as defined below within screening period:
• Haemoglobin ≥9.0 g/dL

You may not qualify if:

• Locally unresectable tumor or metastatic disease:
• Radiological evidence suggesting inability to resect with curative intent whilst maintaining adequate vascular inflow and outflow
• Radiological evidence of direct invasion into adjacent organs.
• Radiological evidence of extrahepatic metastatic disease (except regional lymph nodes - stations 9 and 12
• Contraindication to any of the study drugs
• Any concurrent chemotherapy, investigational product, biologic or hormonal therapy for cancer treatment
• Are currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks or for a period of at least 5 half-lives of the respective drug/IMP (whichever is longer) before screening and during Screening for this trial.
• Have a diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Have a known additional malignancy that is progressing or has required active treatment within the past 2 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Have an active infection requiring systemic therapy (exception: HBV and HCV infection).
• Have a history of Human Immunodeficiency Virus (HIV) (mandatory testing for HIV during screening is required).
• Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Sunnybrook Health Sciences Centre: collaborator
• Hamilton Health Sciences Corporation: collaborator

Study Sites (1)

University Health Network, Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Gemcitabine

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

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 21, 2024
• First Posted: August 26, 2024
• Study Start: December 15, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 26, 2024

Record last verified: 2024-08

Locations

CA (1)