Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig in Resectable iCCA
- Conditions
- Cholangiocarcinoma Resectable
- Registration Number
- NCT06569225
- Lead Sponsor
- University Health Network, Toronto
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not yet recruiting
- Sex
- All
- Target Recruitment
- 40
Inclusion Criteria:<br><br> 1. Patient must be capable of providing written informed consent.<br><br> 2. Age >18 years at time of study entry<br><br> 3. Histologically proven intrahepatic cholangiocarcinoma<br><br> 4. Complete surgical resection of the tumor must be achievable*. Resection should<br> include a portal lymphadenectomy as per standard of care.<br><br> 5. No prior cytotoxic, targeted or immune therapy<br><br> 6. Have provided archival tumor tissue sample or preferably freshly obtained biopsy of<br> a tumor lesion not previously irradiated for mandatory pre-treatment evaluation<br> (baseline).<br><br> 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1<br><br> 8. Estimated life expectancy >3 months<br><br> 9. Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax, bone<br> scan or MRI (if bone metastases are suspected due to clinical signs). Exclusion of<br> the infiltration of any adjacent organs or structures by CT or MRI, indicating an<br> unresectable situation<br><br> 10. If underlying liver cirrhosis, Childs Pugh score of 5 or 6<br><br> 11. If underlying liver disease, ALBI grade =2†<br><br> 12. Patients with HBV infection, which is characterized by positive hepatitis B surface<br> antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV<br> DNA (=10 IU/ml or above the limit of detection per local lab standard), must be<br> treated with antiviral therapy, as per institutional practice, to ensure adequate<br> viral suppression (HBV DNA =2000 IU/mL) prior to study entry. Patients must remain<br> on antiviral therapy for the study duration and for 6 months after the last dose of<br> study medication. Patients who test positive for anti-hepatitis B core (HBc) with<br> undetectable HBV DNA (<10 IU/ml or under limit of detection per local lab standard)<br> do not require anti-viral therapy prior to study entry. These subjects will be<br> tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if<br> HBV DNA is detected (=10 IU/ml or above the limit of detection per local lab<br> standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy<br> for the study duration and for 6 months after the last dose of study medication.<br><br> 13. Patients with HCV infection must have management of this disease per local<br> institutional practice throughout the study. HCV diagnosis is characterized by the<br> presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon<br> enrollment.<br><br> 14. Evidence of post-menopausal status or negative serum pregnancy test for female<br> pre-menopausal patients.<br><br> 15. Adequate normal organ and marrow function as defined below within screening period:<br><br> - Haemoglobin =9.0 g/dL<br><br> - Absolute neutrophil count (ANC =1.0 × 109 /L)<br><br> - Platelet count =100 × 109/L<br><br> - Serum bilirubin =1.5 x institutional upper limit of normal (ULN). <<This will<br> not apply to patients with confirmed Gilbert's syndrome (persistent or<br> recurrent hyperbilirubinemia that is predominantly unconjugated in the absence<br> of hemolysis or hepatic pathology), who will be allowed only in consultation<br> with their physician.<br><br> - AST (SGOT)/ALT (SGPT) =5 x institutional upper limit of normal.<br><br> - Measured creatinine clearance (CL) >50 mL/min or Calculated creatinine<br> clearance<br><br> CL>50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour<br> urine collection for determination of creatinine clearance:<br><br> Males:<br><br> Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)<br><br> Females:<br><br> Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine<br> (mg/dL)<br><br> - Albumin =2.8g/dl<br><br> - International normalized ratio =1.5 (for patients receiving Warfarin, please<br> consult with the study physician)<br><br> 16. Patient is willing and able to comply with the protocol for the duration of the<br> study including undergoing treatment and scheduled visits and examinations including<br> follow up.<br><br> - Resectability is at the discretion of the investigators at each site but must<br> be discussed at a multidisciplinary tumour board.<br><br> - based on albumin and bilirubin; ALBI score = (log10 bilirubin [umol/L]<br> x0.66) + (albumin [g/L] x -0.0852). ALBI grade 1= score = -2.60.<br><br>Exclusion Criteria:<br><br>Patients should not enter the study if any of the following exclusion criteria are<br>fulfilled at time of study enrolment or where indicated:<br><br> 1. Locally unresectable tumor or metastatic disease:<br><br> 1. Radiological evidence suggesting inability to resect with curative intent<br> whilst maintaining adequate vascular inflow and outflow<br><br> 2. Radiological evidence of direct invasion into adjacent organs.<br><br> 3. Radiological evidence of extrahepatic metastatic disease (except regional lymph<br> nodes - stations 9 and 12<br><br> 2. Contraindication to any of the study drugs<br><br> 3. Any concurrent chemotherapy, investigational product, biologic or hormonal therapy<br> for cancer treatment<br><br> 4. Are currently participating in or has participated in a study of an investigational<br> agent or has used an investigational device within 4 weeks or for a period of at<br> least 5 half-lives of the respective drug/IMP (whichever is longer) before screening<br> and during Screening for this trial.<br><br> 5. Have a diagnosis of immunodeficiency or are receiving chronic systemic steroid<br> therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form<br> of immunosuppressive therapy within 7 days prior to the first dose of study drug.<br><br> 6. Have a known additional malignancy that is progressing or has required active<br> treatment within the past 2 years.<br><br> Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of<br> the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that<br> have undergone potentially curative therapy are not excluded.<br><br> 7. Have active autoimmune disease that has required systemic treatment in the past 2<br> years (i.e., with use of disease modifying agents, corticosteroids or<br> immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or<br> physiologic corticosteroid replacement therapy for adrenal or pituitary<br> insufficiency, etc.) is not considered a form of systemic treatment and is allowed.<br><br> 8. Have a history of (non-infectious) pneumonitis/interstitial lung disease that<br> required steroids or has current pneumonitis/interstitial lung disease.<br><br> 9. Have an active infection requiring systemic therapy (exception: HBV and HCV<br> infection).<br><br> 10. Have a history of Human Immunodeficiency Virus (HIV) (mandatory testing for HIV<br> during screening is required).<br><br> 11. Have known psychiatric or substance abuse disorders that would interfere with<br> cooperation with the requirements of the trial.<br><br> 12. Female patients who are pregnant or breastfeeding or male or female patients of<br> reproductive potential who are not willing to employ highly effective birth control<br> from screening to 6 months after the last dose of study treatment. Not engaging in<br> sexual activity, per the patient's preferred and usual lifestyle,
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Major pathological response (MPR), defined as >70% tumor necrosis
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR);The number of patients who experience a surgical delay and/or drop off due to treatment related adverse events (TRAEs) or progressive disease;The number of = grade 3 adverse events (AEs) or immune related adverse events that occur during treatment;Rate of R0