Irinotecan Plus Anlotinib or Further in Combination With Penpulimab for Second-line Treatment of mCRC

NCT ID: NCT05229003

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-09
• Study Completion Date: 2025-12-31

Brief Summary

This is an exploratory, non-controlled, multi-cohort, phase II small-sample clinical study designed to evaluate the clinical benefit of second-line treatment with anlotinib plus irinotecan or further in combination with a PD-1 monoclonal antibody (penpulimab) in patients with advanced colorectal cancer after first-line treatment failure. To explore the rationality of the combination of chemotherapy and targeted therapy and immunotherapy strategy and obtain relevant survival and safety data. The study will fully evaluate the efficacy, PFS, OS, safety and related biomarkers of the regimen.

Detailed Description

The design of this study is an open, non-controlled, multi-cohort, phase II, small-sample prospective clinical study, including eligible patients with metastatic colorectal cancer who received the second-line treatment, and two cohort were included, Cohort A received anlotinib and irinotecan chemotherapy (n=23), and the treatment of cohort B consisted of anlotinib and anti-PD-1 mab (penpulimab) plus irinotecan chemotherapy. Patients were firstly enrolled in cohort A, and if patients in cohort A achieved an response rate of no less than 15% (i.e., no less than 4 out of 23 patients receiving efficacy evaluation achieved CR/PR), the following patients would be enrolled in cohort B. If the response rate of patients in cohort A was less than 15%, subsequent cohort B enrollment (non-control) would be stopped.

A total of 46 patients enrolled in this study, actually.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

cohort A

Anlotinib + Irinotecan:

Anlotinib, 10mg, oral, once daily, D1-10, q2W; Irinotecan, 180mg/m2, iv drip, d6, q2w.

Group Type: EXPERIMENTAL

Anlotinib

Intervention Type: DRUG

Anlotinib 8mg or 10mg, d1-9，q2w

Irinotecan

Intervention Type: DRUG

Irinotecan 180mg/m2, d6, q2w

cohort B

Anlotinib + Penpulimab + Irinotecan:

Anlotinib, 8mg, oral, once daily, d1-10, q2w; Penpulimab 200mg, i.v. d6, q2w; Irinotecan, 180mg/m2, iv infusion, d6, q2w.

Group Type: EXPERIMENTAL

Anlotinib

Intervention Type: DRUG

Anlotinib 8mg or 10mg, d1-9，q2w

Penpulimab

Intervention Type: DRUG

Penpulimab 200mg, d6, q2w

Irinotecan

Intervention Type: DRUG

Irinotecan 180mg/m2, d6, q2w

Interventions

Anlotinib

Anlotinib 8mg or 10mg, d1-9，q2w

Intervention Type: DRUG

Penpulimab

Penpulimab 200mg, d6, q2w

Intervention Type: DRUG

Irinotecan

Irinotecan 180mg/m2, d6, q2w

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Recurrent/metastatic colorectal adenocarcinoma confirmed by histopathological pathology report;

2. The patient received oxaliplatin in combination with fluorouracil as the first-line systemic therapy (with or without anti-EGFR mab or VEGF mab) and failed. Fluorouracil (5-FU, capecitabine, or S-1) and oxaliplatin must be included in the first-line regimens. Treatment failure was defined as: disease progression or intolerable toxicity occurred during treatment or within 3 months after the last treatment; Note: Early adjuvant/neoadjuvant therapy is permitted. If recurrence or metastasis occurs during adjuvant/neoadjuvant therapy or within 6 months after completion, adjuvant/neoadjuvant therapy is considered a failure of first-line chemotherapy for advanced disease;

3. With one or more measurable lesions, the longest diameter measured by spiral CT scan should be at least 10 mm, and the longest diameter measured by conventional CT scan should be at least 20 mm (RECIST standard, version 1.1);

4. the type of KRAS, NRAS, BRAF, and MSI were known, requiring wild type of BRAF. Cohort A required patients with MSS/pMMR status.

5. ECOG score was 0-1;

6. Life expectancy ≥12 weeks;

7. The patient has recovered from damage caused by other anti-tumor therapy, received cytotoxic drugs, radiotherapy or surgery for ≥4 weeks, and the wound has completely healed;

8. Bone marrow capacity and liver and kidney function were sufficiently reserved within 7 days before screening: absolute neutrophil (ANC) count ≥1.5x109 /L; Hemoglobin ≥ 8.0g/ dL; Platelet count ≥80 x109 /L; Total bilirubin < 1.5 times upper normal limit (ULN); ALT and AST< 2.5x ULN (with liver metastasis <5x ULN); Serum creatinine ≤1 x ULN, the clearance rate of endogenous creatinine >50ml/min;

9. Women of childbearing age should take effective contraceptive measures;

10. Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.

Exclusion Criteria

1. A history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;

2. Patients with hypertension that could not be controlled by antihypertensive medication (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg), coronary heart disease of grade I or above, arrhythmia of grade I or above (including prolonged QTc interval > 450ms in males and > 470 ms in females) and cardiac dysfunction of grade I or above;

3. Symptomatic brain or meningeal metastases (unless the patient was treated for >6 months, imaging results were negative within 4 weeks prior to study entry, and tumor-related clinical symptoms were stable at study entry); with a history of uncontrolled epileptic seizures, central nervous system dysfunction, or mental disorders;

4. Uncontrolled pleural or abdominal effusion;

5. Undergoing kidney dialysis;

6. severe or uncontrolled infection;

7. pregnant or lactating women who are fertile but have not taken adequate contraceptive measures;

8. Multiple factors affecting oral medication (inability to swallow, chronic diarrhea and intestinal obstruction);

9. Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg< 2G /L), bleeding tendency or receiving thrombolytic or anticoagulant treatment; patients with gastrointestinal bleeding risk should not be enrolled, including the following conditions :(1) active peptic ulcer lesions and fecal occult blood (++); (2) patients with history of black stools and hematemesis within 3 months;

10. Prior exposure to any anti-PD-1 or anti-PD-L1, PD-L2, CD137, CTLA-4 antibody therapy, or any other antibody or drug that specifically targets T-cell costimulation or immune checkpoint pathways.

11. Former treatment of irinotecan for 1 or more cycles;

12. Prior exposure to any anti-VEGFR small molecule inhibitors (e.g. Apatinib, regorafenib, Fruquintinib, Anlotinib, etc.)

13. Participated in clinical trials of other drugs within four weeks

14. Urine routine examination indicated urine protein > 2+, or 24-hour urine protein quantification ≥1.0g/24h

15. Use of immunosuppressive agents within 4 weeks prior to the first dose of study therapy, excluding nasal, inhaled, or other topical or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/ d of prednisone or equivalent doses of other glucocorticoids), or hormone use for the prevention of contrast agent allergy.

16. Residual liver volume is less than 50% of the total liver volume. -

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Weijian Guo

Director of Department of Medical Gastrointestinal Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weijian Guo, M.D

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Chenchen Wang, M.D

Role: CONTACT

wccnancy2003@aliyun.com

+8613774232040

Facility Contacts

Chenchen Wang, MD

Role: primary

wccnancy2003@aliyun.com

+8613774232040

Other Identifiers

ZL-IRIAN

Identifier Type: -

Identifier Source: org_study_id