GCD9 trial

JRCT ID: jRCTs051240067

Registered date:18/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: biliary tract cancer
• Date of first enrollment: 18/06/2024
• Target sample size: 62
• Study type: Interventional
• Intervention(s): Study subjects enrolled in the study will continue GCD therapy until clinical disease progression or PD by radiological imaging according to RECIST Version 1.1 or intolerance to the study drug.

Outcome(s)

• Primary Outcome: progression free survival

Secondary Outcome

Overall survival
Overall response rate
Duration of treatment
Duration of GCD triple therapy
Dose intensity
Serious adverse event rate
Percentage of adverse reactions (adverse events causally related to the administration of the study treatment) at CTCAE v5.0 grade 3 or above.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Patients who are at least 18 years of age at the time consent is obtained.
(2)Patients with histologically confirmed unresectable advanced or metastatic adenocarcinoma of the biliary system, including intrahepatic and extrahepatic bile duct cancer and gallbladder cancer. However, papillary carcinoma is excluded.
(3) Patients with an expected prognosis of at least 3 months.
(4) If the disease is unresectable or metastatic at the time of initial diagnosis, patients with untreated disease are eligible. However, if surgery for curative purposes is performed, patients who relapse more than six months later and, if applicable, more than six months after completion of postoperative adjuvant therapy (chemotherapy and/or radiotherapy) are eligible.
(5) Patients with a World Health Organization (WHO)/ECOG PS of 0 or 1.
(6) Patients with at least one target lesion as per the new guidelines for determining response to treatment of solid tumors (RECIST) edition 1.1.
(7) Patients with no prior immunotherapy with anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies, including but not limited to. However, anti-cancer vaccines used for therapeutic purposes are excluded.
(8) Patients with adequate organ function, bone marrow function and coagulation capacity who fulfil the following conditions.
Hb 9.0 g and more
Absolute neutrophil count 1500 and more
Platelet count 100000 and more
Serum bilirubin 2.0 and less times the upper limit of the institutional reference value (ULN).
This condition does not apply to patients with a confirmed diagnosis of Gilbert's syndrome, but the clinically problematic bile duct obstruction must be corrected.
ALT and AST less than 2.5 times the ULN. For patients with liver metastases, ALT and AST less than 5 times the ULN.
Patients with creatinine clearance more than 50 mL/min based on 24 hour urine collection or calculated using the Cockcroft-Gault formula below (using actual body weight).
(9) Body weight more than 30 kg.
(10) Patients who are competent to comply with the requirements and limitations described in the consent document and the study protocol and have signed the consent document in their own handwriting.

Exclude criteria

(1) Patients with tumours originating in the vastus diaphragmaticus (duodenal papillary region).
(2) Patients with a history of allogeneic organ transplantation.
(3) Patients with current or previous autoimmune or inflammatory diseases (inflammatory bowel disease [e.g. colitis or Crohn's disease]), diverticulitis except diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome or Wegener's syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis etc. are identified patients. However, the following may be included.
Patients with vitiligo or alopecia.
Patients with hypothyroidism (e.g. after Hashimoto's disease), which is stable during hormone replacement therapy.
Patients with chronic skin diseases not requiring systemic treatment.
Patients with no active disease within 5 years prior to consent.
Patients with coeliac disease controlled by diet alone.
(4) Patients with poorly controlled co-morbidities such as, but not limited to, uncured or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, poorly controlled arrhythmias, active interstitial lung disease (ILD) and severe chronic gastrointestinal disease with diarrhoea. (but not limited to).
(5) Patients with a history of another primary malignancy. However, the following are excluded.
Malignant tumours that have been treated with the aim of cure, have not been confirmed as active for at least 5 years prior to the start of treatment in this study and have a low risk of recurrence.
Skin cancers other than melanoma or lentigo maligna that have been adequately treated and for which there is no evidence of disease.
Intraepithelial carcinoma that has been adequately treated and for which there is no evidence of disease.
(6) Patients with a history of soft meningeal carcinomatosis.
(7) Patients with a history of active primary immunodeficiency.
(8) Patients with active infectious diseases such as tuberculosis (TB confirmed by history, clinical evaluation including examination and radiological findings and TB test) or human immunodeficiency virus (HIV 1/2 antibody positive).
(9) Patients who have not had resolution of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher toxicity (excluding alopecia, vitiligo vulgaris and laboratory tests specified in the selection criteria) resulting from previous anticancer therapy.
However, the following are excluded
a.Patients who develop grade 2 or higher neuropathy can be individually assessed and included only after consultation with the study office.
b.Patients with irreversible toxicities that it is reasonable to expect will not be exacerbated by the administration of gemcitabine, cisplatin or durvalumab may be individually assessed and included only after consultation with the study office.
(10) Patients with brain metastases or spinal cord compression (including asymptomatic and appropriately treated disease).
In patients with suspected brain metastases at screening, an MRI (recommended) or CT scan of the brain should be performed prior to enrolment (both tests should be performed using intravenous contrast media).
(11) Patients with known allergy or hypersensitivity to gemcitabine, cisplatin, durvalumab or their additives.
(12) Patients receiving any combination of chemotherapy, investigational therapy, biologic or hormonal therapy for the treatment of cancer. However, concomitant hormonal therapy for diseases unrelated to cancer (e.g. hormone replacement therapy) is permitted.
(13) Radiotherapy, including palliative radiotherapy, is not permitted prior to enrolment, except for radiation administered as adjuvant postoperative therapy.
(14) Patients who have received attenuated live attenuated vaccine within 30 days prior to the first dose of study drug.
Note that post-registration patients may not be vaccinated with live vaccine during the study drug administration period and for up to 90 days after the last dose of study drug.
(15) Patients who have undergone major surgery (subject to the decision of the principal (sub)investigator) within 28 days prior to the first dose of study drug. Note that simple surgery of isolated lesions for palliative purposes performed before 14 days prior to the first study drug administration is acceptable.
(16) Patients currently using or who have used immunosuppressive drugs within 14 days prior to the first dose of study drug.
However, the following are acceptable for inclusion.
Nasal, inhaled or topical steroids or local steroid injections (e.g. intra-articular injections).
Physiological doses of systemic corticosteroids not exceeding prednisone 10 mg/day or equivalent.
Steroids as premedication for hypersensitivity reactions (e.g. premedication for CT scan).
(17) Patients who are included in other clinical trials concurrently with the present study, unless they are in an observational (non-interventional) clinical trial or in the follow-up period of an interventional trial.
(18) Pregnant or lactating female patients, or male or female patients of reproductive potential who are unwilling to use an effective contraceptive method from screening until 90 days after the last dose.
(19) Patients with active HBV infection (hepatitis B).
(20) Patients with hepatitis C virus (HCV) RNA levels detectable by the respective implementing healthcare laboratory and found to be suffering from active infection with HCV.
Note that patients with a positive hepatitis C (HCV) antibody test but no detectable HCV RNA may be included.
(21) Patients who cannot comply with the study procedures, limitations and requirements and are judged by the principal (sub)investigator to be unsuitable to participate in the study.
(22) Patients who are deemed by the principal (sub)investigator to be ineligible to participate in the study.

Related Information

• Primary Sponsor: Kitano Masayuki
• Source(s) of Monetary Support: AstraZeneca K.K.