Locally advanced (T3-4 N0-1) rectal cancer. MedDRA version: 21.0 Level: PT Classification code 10038019 Term: Rectal adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Durvalumab
Product Code: [MEDI4736]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Oth
Sponsors
AZIENDA UNITÀ SANITARIA LOCALE DELLA ROMAGNA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and Data Privacy Directive obtained from the patient/legal representative prior to performing any protocol- related procedures, including screening evaluations. 2. Age > 18 years at time of study entry. 3. Eastern Cooperative Oncology Group (ECOG) 0 or 1. 4. Histological diagnosis of adenocarcinoma of rectum. 5. Clinical stage 2-3 rectal adenocarcinoma, cT3/4N0/M0 or Tx N1-2/M0, assessed by thorax abdomen pelvis with contrast Computed tomography (CT) scan, pelvi Magnetic resonance imaging (MRI) scan, pancolonscopy. 6. Able to swallow oral medication. 7. Body weight >30kg. 8. Adequate normal organ and marrow function as defined below: • Haemoglobin =9.0 g/dL • Absolute neutrophil count (ANC) > 1500 per mm3 • Platelet count >100.000 per mm3 • Serum bilirubin =1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician. • AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976). 9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients. Women of childbaring potential or male patients with a female partner of childbearing potential must agree to use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after the last dose of durvalumab monotherapy) as detailed in section 7.1. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply: • Women 1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 11. Must have a life expectancy of at least 12 weeks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. Previous treatment for local advanced rectum cancer. 2. Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. 3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab. 4. History of hypersensitivity to fluorouracil. 5. Known Dihydropyrimidine dehydrogenase (DPD) deficiency. 6. History of another primary malignancy except for: - Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drug and of low potential risk for recurrence - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ 7. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion: - Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) - Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 9. Major surgical procedure within 28 days prior to the first dose of treatment. 10. Uncontrolled intercurrent illness
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Determine safety of treatment with durvalumab in terms of number and the percentage of patients with every type of event; proportion of patients with complete clinical response and corresponding confidence intervals after durvalumab treatment.; DFS is defined as time since surgery until disease occurrence or death, whichever occur first, or last follow-up and will be estimated by using Kaplan-Meier approach;Timepoint(s) of evaluation of this end point: After 21 months from study start; 18 months after study start; 6 years | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the pathological complete response rate (pCR) in patients with rectal cancer treated with standard neo-adjuvant chemotherapy with capecitabine and radiation followed by durvalumab and surgery.;Secondary Objective: 1.Determine safety of treatment with durvalumab; 2.Determine clinical complete remission rate (cCR) after durvalumab treatment, before surgery; 3.Determine disease-free survival (DFS).;Primary end point(s): proportion of patients with complete pathological response and corresponding confidence intervals after durvalumab treatment.;Timepoint(s) of evaluation of this end point: 18 months after study start | — |
Countries
Italy
Contacts
Public ContactCentro di Coordinamento Studi Clini
IRST IRCCS
Outcome results
None listed