Clinical trial NCT04380103: A Phase I/II Study of XELOXIRI and Bevacizumab as First-line Treatment in Metastatic Colorectal Cancer
Official title: A Phase I/II Study of Irinotecan, Oxaliplatin, Capecitabine (XELOXIRI) and Bevacizumab as a First-line Therapy for Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Metastatic Cancer
Colorectal Cancer
Colorectal Adenocarcinoma
Keywords: metastatic colorectal cancer
metastatic colorectal adenocarcinoma
XELOXIRI
bevacizumab
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2020-05-08
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The phase I/II study was designed to evaluate if the regimen of Irinotecan, Oxaliplatin, Capecitabine (XELOXIRI) and Bevacizumab is a superior first-line option for patients with metastatic colorectal cancer(mCRC) in terms of safety and efficacy.

Detailed description: Recent studies have shown that the triplet-drug regimen FOLFOXIRI (irinotecan/oxaliplatin/fluorouracil) can further improves survival benefit for patients with metastatic colorectal cancer(mCRC) compared to standard two-drug regimens in first-line therapy, especially when combined with bevacizumab. However, the increased toxicities of FOLFOXIRI limited its usage. Capecitabine demonstrates a superior efficacy and safety than fluorouracil, so we designed this trial to evaluate if the XELOXIRI plus bevacizumab can be a better alternative to FOLFOXIRI plus bevacizumab. The phase I study is to determine the safety and the recommended phase II dose (RP2D) of XELOXIRI plus Bevacizumab. In the phase II study, we aim to determine the efficacy of the regimen as first-line therapy for mCRC and explore potential molecular biomarkers (genomes, circulating tumor cell) for toxicity forecasting or efficacy monitoring.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically confirmed metastatic colorectal adenocarcinoma;
* Age 18-80 years old;
* Eastern Cooperation Oncology Group (ECOG) performance score(\<2);
* At least one measurable lesion for disease assessment according to RECIST version 1.1;
* Able to take oral medications;
* Previous fluoropyrimidine-based adjuvant or neoadjuvant chemotherapy was allowed only when it ended ≥ 6 months before study enrollment;
* No previous therapy for mCRC;
* Adequate organ functions as assessed by the following laboratory requirements: Leukocytes≥3.0x109/L, absolute neutrophil count≥1.5x109/L, platelet count≥100x109/L, hemoglobin≥9g/dL; serum bilirubin≤1.5x the upper limit of normal(ULN);Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤3x ULN; serum creatinine≤1.5x ULN; calculated creatinine clearance or 24 hour creatinine clearance ≥60ml/min.
* An expected survival of at least 3 months;
* Willingly provide written informed consent to study procedures.

Exclusion Criteria:

* Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
* With a history of extensive enterotomy or pelvic radiation therapy; Suffering from grade 2 or higher symptomatic peripheral neuropathy according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
* Uncontrolled central nervous system metastasis, disseminated intravascular coagulation or active infection;
* With concurrent cancer distinct from colorectal adenocarcinoma except cured skin basal cell carcinoma and cervical carcinoma in situ;
* Undergone a major operation, open biopsy or major traumatic injury within 28 days before study enrollment or have potential to receive major operation during the trial;
* Received central venous access device within 2 days before study enrollment;
* Any kind of concurrent cardiac disease with clinical meanings, such as cardiovascular accident, myocardial infarction, thromboembolism or hemorrhage within 6 months before enrollment, congestive heart failure ≤New York Heart Association (NYHA) class 2 or uncontrolled hypertension.
* With positive urine protein and 24-hour urinary protein content\>1g;
* Have a tendency of bleeding or clotting;
* With nasty open wounds, ulcers or fractures;
* Current or recent treatment of anticoagulants, antiplatelet agent or nonsteroidal anti-inflammatory drugs, while aspirin of daily dose less than 325mg is allowed.
* With any illness or medical conditions that may jeopardize the patient's compliance or interfere the analyses or judgements of study results;
* Pregnancy or lactation at the time of study entry;
* With fertility but refuse to contraception.

Primary outcomes:
measure: dose-limited toxicity (DLT)
timeFrame: up to 1 year
measure: maximum tolerated dose (MTD)
timeFrame: up to 1 year
measure: recommended phase 2 dose (RP2D)
timeFrame: up to 1 year
measure: objective response rate (ORR)
timeFrame: up to 2 years
Secondary outcomes:
measure: Adverse events (AEs)
timeFrame: though study completion, an average of 2 years
measure: progression-free survival (PFS)
timeFrame: though study completion, an average of 2 years
measure: overall survival (OS)
timeFrame: up to 5 years
measure: disease control rate (DCR)
timeFrame: up to 2 years
measure: duration of response (DOR)
timeFrame: though study completion, an average of 2 years
measure: time to response (TTR)
timeFrame: up to 2 years
measure: the surgical resection rate of patients with liver-only metastases
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Center/Cancer Hospital, China Academy of Medical Science and Peking Union Medical College
city: Beijing
country: China
facility: National Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: Lin Yang
role: PRINCIPAL_INVESTIGATOR
References: