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Official Title

A Phase II Trial of Durvalumab With Gemcitabine and Cisplatin as Neoadjuvant Therapy for High-Risk Resectable Intrahepatic Cholangiocarcinoma

Phase
Phase 2
Sponsor
National Cancer Institute (NCI)
Enrollment
27
Timeline
Jul 2024 → Feb 2026
About This Study

This phase II trial tests how well giving durvalumab with standard chemotherapy, gemcitabine and cisplatin, before surgery works in treating patients with high risk liver cancer (cholangiocarcinoma) that can be removed by surgery (resectable). Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab with gemcitabine and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed in patients with high risk resectable cholangiocarcinoma.

Eligibility Criteria

Inclusion Criteria

  • 1Patients must have histologically or cytologically confirmed intrahepatic cholangiocarcinoma (iCCA) that is resectable by imaging evaluation. Choice of staging modality is left up to the discretion of the treatment team; we favor high-quality CT scan of the chest/abdomen/pelvis with liver or biliary protocol. Eligibility will be confirmed through central imaging review.
  • 2Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam.
  • 3Patients must be an acceptable risk surgical candidate at the time of enrollment, as determined by a board-certified surgeon with expertise in hepatobiliary surgery.
  • 4High-risk iCCA is defined as the presence of any of these factors:
  • 5Tumor size \> 5 cm.
  • 6Multifocality or satellitosis limited to the same lobe.
  • 7Vascular invasion.
  • 8Suspected or confirmed (via biopsy) regional lymph node metastases.
  • 9Suspected is defined as lymph nodes that are deemed suspicious for metastasis based on large size (criteria vary per anatomical location; 6-10 mm for abdominal and 8-10 mm for pelvic), enhancement pattern, and shape. These may also include lymph nodes that display fludeoxyglucose F 18 (FDG)-avidity on positron emission tomography (PET) scan, if obtained, in the course of disease work-up (not mandatory).
  • 10CA 19-9 \> 200 U/mL.
  • 11Patients are treatment naïve for iCCA.
  • 12Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of durvalumab (MEDI4736) in combination with cisplatin and gemcitabine in patients \< 18 years of age, children are excluded from this study.
  • 13Body weight \> 30 kg.
  • 14Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%).
  • 15Leukocytes \>= 3,000/mcL.
  • 16Hemoglobin \>= 9.0 g/dL.
  • 17Absolute neutrophil count \>= 1,500/mcL.
  • 18Platelets \>= 100,000/mcL.
  • 19Neuropathy grade =\< 1 by CTCAE.
  • 20Albumin \>= 2.8 g/dL.
  • 21Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN).
  • 22Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 × institutional ULN.
  • 23Serum creatinine =\< 1.5 x institutional ULN.
  • 24Measured creatinine clearance \> 60 mL/min or glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 (by the Cockcroft-Gault equation).
  • 25Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • 26Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • 27Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • 28Life expectancy \>= 12 weeks.
  • 29Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • 30For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • 31Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • 32Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • 33Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. If non-protocol anticancer agents for non-study indications is required concurrently with the protocol therapy, the case should be discussed and approved by the study chair and the sponsor (Cancer Therapy Evaluation Program \[CTEP\]).
  • 34Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
  • 35Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria

  • 1Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
  • 2Major surgical procedure (as defined by the Investigator) within 14 days prior to the first dose of durvalumab. Note: Local surgery of isolated lesions for palliative intent or biliary stents is acceptable.
  • 3Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • 4Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
  • 5Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent.
  • 6Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • 7Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab.
  • 8Patients who are receiving any other investigational agents.
  • 9History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab, gemcitabine, cisplatin, or other platinum-containing compounds.
  • 10Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous.
  • 11Pregnant women are excluded from this study because durvalumab (MEDI4736) is an anti-PD-L1 monoclonal antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab, breastfeeding should be discontinued if the mother is treated with durvalumab. These potential risks may also apply to other agents used in this study. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after durvalumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of durvalumab.
  • 12Patients with 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:
  • 13Patients with vitiligo or alopecia.
  • 14Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.
  • 15Any chronic skin condition that does not require systemic therapy.
  • 16Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  • 17Patients with celiac disease controlled by diet alone.
  • 18Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • 19History of allogenic organ transplantation.
  • 20Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Locations

58 sites participating in this study

Emory University Hospital Midtown

Atlanta, Georgia 30308

Recruiting

Seth Concors

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

Recruiting

Seth Concors

Emory Saint Joseph's Hospital

Atlanta, Georgia 30342

Recruiting

Seth Concors

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →