DURVALUMAB for Locally advanced rectal cancer

Inclusion criteria

• {"criterion_text":"-\tWritten informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.\n-\tAdequate normal organ and marrow function\n-\tEvidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients\n-\tPatient 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.\n-\tAge ≥ 18 years at time of study entry.\n-\tEastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n-\tBody weight >30kg.\n-\tBiopsy-proven, newly diagnosed primary rectal adenocarcinoma, with the lowest part of the tumour less than 12 cm from the anal verge using a rigid rectoscope or flexible endoscope.\n-\tMSS (microsatellite stable) rectal cancer assessed by local practice (immunohistochemistry or PCR).\n-\tMandatory tumour and blood samples for translational research.\n-\tHigh risk MRI-defined rectal cancer\n-\tNo contraindications to chemotherapy and radiotherapy."}

Exclusion criteria

• {"criterion_text":"-\tParticipation in another clinical study with an investigational product during the last 6 months.\n-\tAny previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.\n-\tMean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s Correction.\n-\tCurrent or prior use of immunosuppressive medication within 28 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.\n-\tAny unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria\n-\tAny 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.\n-\tPrevious radiotherapy in the pelvic region (e.g. prostate) or previous rectal surgery (e.g.TEM).\n-\tHistory of allogenic organ transplantation.\n-\tActive 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]).\n-\tUncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.\n-\tHistory of another primary malignancy\n-\tConcurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.\n-\tFemale patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab monotherapy.\n-\tHistory of active primary immunodeficiency.\n-\tActive infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). 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.\n-\tReceipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.\n-\tKnown allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.\n-\tJudgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.\n-\tKnown allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.\n-\tPrior therapy for rectal cancer.\n-\tPresence of metastatic disease or recurrent rectal tumour. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn’s disease or active ulcerative Colitis.\n-\tMSI (microsatellite inestable) rectal cancers assessed by local practice (immunohistochemistry or PCR).\n-\tExtensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is seen.\n-\tKnown DPD deficiency\n-\tPersistent peripheral neural toxicity > grade 2.\n-\tIntestinal occlusion. Patients with intestinal occlusion due to the primary rectal tumour, that could participate in the study, may be included after a derivative intestinal surgery."}

Primary endpoints

• {"endpoint_text":"-\t1)\tPathological complete response (pCR) rate.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"-\t1)\tTumor downstaging.","definition_or_measurement_approach":""}
• {"endpoint_text":"-\t2)\tTumor regression grade (TGR).","definition_or_measurement_approach":""}
• {"endpoint_text":"-\t3)\tR0 resection rate.","definition_or_measurement_approach":""}
• {"endpoint_text":"-\t4)\tClear circumferential resection margin (CRM) rate.","definition_or_measurement_approach":""}
• {"endpoint_text":"-\t5)\t3-year disease-free survival (DFS).","definition_or_measurement_approach":""}
• {"endpoint_text":"-\t6)\tToxicity profile (short and long-term).","definition_or_measurement_approach":""}
• {"endpoint_text":"-\t7)\tReduction of surgical complications.","definition_or_measurement_approach":""}
• {"endpoint_text":"-\t8)\tCalculation of the neoadjuvant rectal (NAR) score","definition_or_measurement_approach":""}

Spain

Earliest CTIS Part Ii Submission Date

13-11-2024

Latest Decision Or Authorization Date

23-10-2025

Processing Time Days

344

Number Of Sites

10

Number Of Participants

60

Primary sponsor

Full Name

Grupo Espanol Multidisciplinar En Cancer Digestivo

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Vall D Hebron Institute Of Oncology","duties_or_roles":"1,10,11,12,14,4,5,8","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Spain","full_name":"Lodilat Logistica S.L.","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}