Clinical trial NCT05945901: A Phase II/III Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer
Official title: A Phase II/III, Double-blind, Randomized, Multi-center Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Colorectal Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-14
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomized, multi-center, II/III study in at least 606 patients with advanced colorectal cancer. The study is being conducted to evaluate the safety of HR070803 combined with oxaliplatin, 5-FU/LV and bevacizumab in phase II and to evaluate the efficacy of HR070803 in combination with oxaliplatin, 5-FU/LV, and bevacizumab versus HR070803 simulator in combination with FOLFOX and bevacizumab for first-line treatment of patients with unresectable metastatic colorectal cancer.


Eligibility criteria: Inclusion Criteria:

1. Male or female who is 18-75 years of age;
2. Histologically-confirmed metastatic and unresectable (Stage IV as defined by American Joint Committee on Cancer \[AJCC eighth edition\]) colorectal adenocarcinoma
3. No previous systemic antitumor therapy (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biotherapy, and other investigational therapeutic agents) for colorectal cancer (patients with confirmed relapse ≥6 months after the last administration of neoadjuvant or adjuvant therapy can be enrolled);
4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 ;
5. Life expectancy of ≥ 6 months;
6. Vital organ functions meet the criteria.

Exclusion Criteria:

1. With confirmed MMR deficient (dMMR) or microsatellite instability high (MSI-H).
2. With central nervous system metastases.
3. Previous oxaliplatin-containing chemotherapy within 12 months prior to enrolment.
4. Previous treatment with irinotecan, immune checkpoint inhibitor, anti-epidermal growth factor receptor or any anti-angiogenic drug.
5. Patients with large amount of pleural effusion, ascites or pericardial effusion that could not reach a stable state within 2 weeks prior to enrolment.
6. Severe gastrointestinal dysfunction (inflammation or diarrhea \> grade 1).
7. With diagnosed interstitial lung disease.
8. Severe cardiovascular and cerebrovascular diseases.
9. Peripheral neuropathy \> grade 1.
10. Intestinal obstruction within the 6 months prior to enrolment.
11. Gastrointestinal perforation, gastrointestinal fistula, intraperitoneal abscess, and non-gastrointestinal fistula (e.g. tracheoesophageal fistula) within 6 months prior to enrolment.
12. Patients with CTCAE≥ grade 3 gastrointestinal bleeding within 6 months prior to enrolment, or any grade gastrointestinal bleeding within 1 month prior to enrolment.
13. Patients with CTCAE≥ grade 3 extra-gastrointestinal bleeding within 6 months prior to enrolment, or CTCAE≥ grade 2 extra-gastrointestinal bleeding within 3 months prior to enrolment.
14. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg under regular antihypertensive therapy), and a history of hypertensive crisis or hypertensive encephalopathy.
15. History of hypersensitivity or contraindications to any of irinotecan liposomes/simulator, irinotecan, other liposomal products, 5-FU, calcium folinate, oxaliplatin, bevacizumab.

Primary outcomes:
measure: Adverse Events (AE) According to NCI-CTCAE v5.0（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Serious Adverse Events (SAE)（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Progression-Free Survival (PFS) Assessed by IRC（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
Secondary outcomes:
measure: Overall Response Rate (ORR) Assessed by investigator（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Disease Control Rate (DCR) by investigator（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Duration of Overall Response (DoR) by investigator（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Progression-Free Survival (PFS) Assessed by investigator（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Overall Survival (OS)（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Characterize the PK（Phase II）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Overall Survival (OS)（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Progression-Free Survival (PFS) Assessed by investigator（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Overall Response Rate (ORR) Assessed by IRC and investigator（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Duration of Overall Response (DoR) by IRC and investigator（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Disease Control Rate（DCR） by IRC and investigator（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Adverse Events (AE) According to NCI-CTCAE v5.0（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
measure: Serious Adverse Events (SAE)（Phase III）
timeFrame: From Baseline to primary completion date, about 48 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdog
Study officials:
References: