Assessing the impact of mouth and bowel bacteria on outcomes of patients receiving chemotherapy with immunotherapy
- Conditions
- Biliary tract adenocarcinoma, including cholangiocarcinoma (intra- and extra-hepatic biliary ducts), and gallbladder carcinomaCancer
- Registration Number
- ISRCTN11210442
- Lead Sponsor
- Christie Hospital NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 70
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
2. Provision of a signed and dated written ICF prior to any mandatory study-specific procedures, sampling, and analyses
3. Provision of a signed and dated written informed consent prior to the collection of samples (saliva and stool) for analysis
4. Age =18 years at the time of screening
5. Histologically biopsy-confirmed (not cytology brushings), unresectable advanced or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma
6. Patients with previously untreated disease if unresectable or metastatic at initial diagnosis will be eligible
7. Patients who developed recurrent disease >6 months after surgery with curative intent and, if given, >6 months after the completion of adjuvant therapy (chemotherapy and/or radiotherapy) will be eligible
8. Eastern Co-operative Oncology Group Performance Status (ECOG PS) of 0 or 1 at enrolment
9. At least 1 lesion that qualifies as a Response Evaluation Criteria RECIST 1.1 Target Lesion (TL) at baseline
10. No prior exposure to immune-mediated therapy, including, but not limited to, other Anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines
11. Adequate organ and marrow function, as defined below:
11.1. Haemoglobin =9.0 g/dL
11.2. Absolute neutrophil count =1.5 × 109/L
11.3. Platelet count =100 × 109/L
11.4. Serum bilirubin =1.5 × the institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician
11.5. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =2.5 × ULN; for patients with hepatic metastases, ALT and/or AST =5 × ULN
11.6. Measured creatinine clearance (CL) >50 mL/min or calculated creatinine clearance (CL) >50 mL/min as determined by Cockcroft-Gault (using actual body weight):
11.6.1. Males: Creatinine CL (mL/min) = Weight (kg) x (140-Age)/72 x serum creatinine (mg/dL)
11.6.2. Females: Creatinine CL (mL/min) = Weight (kg) x (140-Age) x 0.85/72 x serum creatinine (mg/dL)
12. Patients must have a life expectancy of at least 12 weeks at the time of screening
13. Body weight >30 kg
14. Patients must have a recent tumour biopsy or an available unstained archived tumour tissue sample in a quantity sufficient to allow for future analysis. The tumour lesions used for biopsy (if recent) should not be those used as RECIST TLs, unless there are no other lesions suitable for biopsy
15. Patients with HBV infection (as characterised by positive hepatitis B surface antigen [HBsAg] and/or anti-hepatitis B core antibodies (anti-HBc) with detectable HBV deoxyribonucleic acid (DNA) [=10 IU/mL or above the limit of detection per local laboratory]) must receive antiviral therapy prior to registration per institutional practice to ensure adequate viral suppression. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. Patients who test positive for anti-HBc with undetectable HBV DNA (<10 IU/mL or under the limit of detection per local laboratory) do not require antiviral therapy unless HBV DNA exceeds 10IU/mL or
1. Ampullary carcinoma or combined or mixed hepatocellular/cholangiocarcinoma
2. History of allogeneic organ transplantation
3. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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 are:
3.1. Patients with vitiligo or alopecia
3.2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
3.3. Any chronic skin condition that does not require systemic therapy
3.4. Patients without an active disease in the last 5 years may be included but only after consultation with the study physician
3.5. Patients with coeliac disease controlled by diet alone
4. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring Adverse Events (AEs), or compromise the ability of the patient to give written informed consent.
5. History of another primary malignancy, except for:
5.1. Malignancy treated with curative intent and with no known active disease =5 years before the first dose of investigational medicinal product (IMP) and of low potential risk for recurrence
5.2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
5.3. Adequately treated carcinoma in situ without evidence of disease
6. History of leptomeningeal carcinomatosis
7. History of active primary immunodeficiency
8. Active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), or human immunodeficiency virus (positive HIV 1/2 antibodies).
9. Any unresolved toxicity National Cancer Institute Common Terminology Criteria (CTC) for Adverse Event (NCI CTCAE) Grade =2 from a previous anticancer therapy, with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
9.1. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.
9.2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician.
10. Brain metastases or spinal cord compression (including asymptomatic and adequately treated disease). Patients with suspected brain metastases at screening should have a Magnetic Resonance Imaging (MRI) scan (preferred) or CT scan, each preferably with IV contrast, of the brain prior to study entry.
11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
12. Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
13. Concurrent palliative radiotherapy involving ta
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method umber of species present in microbiome samples (baseline alpha diversity) from both responders” (best response of partial or complete response) and non-responders”, defined using RECIST 1.1criteria, measured microbiome analysis at 18 weeks
- Secondary Outcome Measures
Name Time Method The following secondary outcomes will be measured according to RECIST 1.1 criteria and recorded in patient medical notes for the duration of the study, with follow-up until 12 months after the last patient is enrolled:<br>1. Objective response rate<br>2. Disease control rate<br>3. Progression-free survival<br>4. Overall survival