Metastatic Microsatellite-Stable Colorectal Cancer MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. • Age = 18 years at the time of screening. • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. • Patients must have histologic documentation of advanced or metastatic colorectal cancer and: - A documented mutation test during screening and confirmed tumor locations from disease assessment for enrollment. - Patients must NOT have defective DNA mismatch repair (microsatellite instability) as documented by testing. - Patients must not have received any prior systemic therapy for recurrent/metastatic disease (prior adjuvant chemotherapy or radio-chemotherapy is acceptable so long as progression was not within 6 months of completing the adjuvant regimen). • Patients must have at least one lesion that is measurable by RECIST v1.1 (Eisenhauer et al, 2009). • Patients must have adequate organ function. • Patients with medical conditions requiring systemic anticoagulation (eg, atrial fibrillation) are eligible provided that both of the following criteria are met: - The patient has an in-range international normalized ratio (INR) on a stable dose of oral anticoagulant or be on a stable dose of low molecular weight heparin. - The patient has no active bleeding or pathological condition that carries a high risk of bleeding. • Body weight > 35 kg. • Adequate method of contraception per protocol. 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 53 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 53
Exclusion criteria
Exclusion criteria: • History of allogeneic organ transplantation. • Active or prior documented autoimmune disorders within the past 5 years • History of venous thrombosis within the past 3 months • Cardiovascular criteria: - Presence of acute coronary syndrome including myocardial infarction or unstable angina pectoris, other arterial thrombotic event including cerebrovascular accident or transient ischemic attack or stroke within the past 6 months. - New York Heart Association (NYHA) class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension. - History of hypertensive crisis/hypertensive encephalopathy within the past 6 months • Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) = 470 ms • No significant history of bleeding events or gastrointestinal perforation • Uncontrolled intercurrent illness • History of another primary malignancy except for: - Malignancy treated with curative intent and with no known active disease = 5 years 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. • History of active primary immunodeficiency • Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. • Any unresolved toxicity NCI CTCAE Grade > 1 from previous anticancer therapy. • History of leptomeningeal disease or cord compression. • Untreated central nervous system (CNS) metastases • Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication. • Known dihydropyrimidine dehydrogenase (DPD) deficiency. • Prior immunotherapy or anti-angiogenics. • Receipt of live attenuated vaccine within the past 30 days. • Major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days. • Current or prior use of immunosuppressive medication within the past 14 days, with exceptions per protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To evaluate the safety and tolerability profile of FOLFOX + bevacizumab + novel oncology therapy combinations Part 2: To compare the efficacy of FOLFOX + bevacizumab + novel oncology therapy combinations versus FOLFOX + bevacizumab ; Secondary Objective: Part 1 & 2: To investigate the preliminary antitumor activity of FOLFOX + bevacizumab+ novel oncology therapy combinations To describe the PK of novel agents when used in combination with FOLFOX + bevacizumab. To describe the PK of bevacizumab when used in combination with FOLFOX + novel oncology therapy combinations To assess the immunogenicity of applicable novel agents when used in combination with FOLFOX + bevacizumab. To assess the immunogenicity of bevacizumab when used in combination with FOLFOX + novel oncology therapy combinations Part 2: To evaluate the safety and tolerability profile of FOLFOX + bevacizumab + novel oncology therapy combinations ; Primary end point(s): Part 1: Incidence of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), laboratory findings, and vital signs Part 2: Objective response (OR) per RECIST v1.1 ; Timepoint(s) of evaluation of this end point: Safety observed from informed consent through 90 days after the last dose of investigational product. Dose-limiting toxicities will be evaluated during the safety run-in phase (Part 1). The DLT evaluation period is defined as 28 days from the first dose of investigational product (novel therapy). Efficacy will be assessed every 8 weeks through 1 year then every 12 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: Objective response (OR), best overall response (BOR), duration of response (DoR), disease control (DC), progression-free survival-12 (PFS-12), progression-free survival (PFS) per RECIST v1.1, and overall survival (OS) Part 1 & 2: PK (drug concentration) and incidence of antidrug antibodies (ADA) Part 2: Incidence of adverse events (AEs), serious adverse events (SAEs), laboratory findings, and vital signs Part 2: BOR, DoR, DC, PFS-12 and PFS per RECIST v1.1,and overall survival (OS) ; Timepoint(s) of evaluation of this end point: Efficacy endpoints assessed from screening until 18 months post last dose, then every 6 months. PK from Day 1 until Week 53. ADA from Day 1 until 90 days post last dose. | — |
Countries
Australia, Canada, France, Spain, United States
Contacts
Public ContactClinical Trial Transparency
AstraZeneca AB
Outcome results
None listed