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

NCT05229003 | Recruiting Phase 2

• 1 other identifier: ZL-IRIAN
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; second-line treatment; target therapy; enlotinib; penpulimab

Outcome Measures

Primary Outcomes (1)

• ORR

  objective response rate

  the rate of patients with CR and PR, through study completion, an average of 1 year

Secondary Outcomes (5)

• PFS

  from the time signing of ICF until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

• OS

  from the time signing of ICF until the date of death from any cause, assessed up to 36 months

• DoR

  the time between the first tumor evaluation for CR or PR and the first evaluation for PD(Progressive Disease) or death from any cause, assessed up to 36 months

• DCR

  the rate of patients with CR, PR and SD, through study completion, an average of 1 year

• AEs

  the adverse events rate and types of all enrolled patients, through study completion, an average of 1 year

Study Arms (2)

cohort A

EXPERIMENTAL

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

Drug: Anlotinib; Drug: Irinotecan

cohort B

EXPERIMENTAL

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

Drug: Anlotinib; Drug: Penpulimab; Drug: Irinotecan

Interventions

Anlotinib DRUG

Anlotinib 8mg or 10mg, d1-9，q2w

cohort A; cohort B

Penpulimab DRUG

Penpulimab 200mg, d6, q2w

cohort B

Irinotecan DRUG

Irinotecan 180mg/m2, d6, q2w

cohort A; cohort B

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent/metastatic colorectal adenocarcinoma confirmed by histopathological pathology report;
• 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;
• 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);
• the type of KRAS, NRAS, BRAF, and MSI were known, requiring wild type of BRAF. Cohort A required patients with MSS/pMMR status.
• ECOG score was 0-1;
• Life expectancy ≥12 weeks;
• 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;
• 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;
• Women of childbearing age should take effective contraceptive measures;
• Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.

You may not qualify if:

• A history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;
• 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;
• 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;
• Uncontrolled pleural or abdominal effusion;
• Undergoing kidney dialysis;
• severe or uncontrolled infection;
• pregnant or lactating women who are fertile but have not taken adequate contraceptive measures;
• Multiple factors affecting oral medication (inability to swallow, chronic diarrhea and intestinal obstruction);
• 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;
• 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.
• Former treatment of irinotecan for 1 or more cycles;
• Prior exposure to any anti-VEGFR small molecule inhibitors (e.g. Apatinib, regorafenib, Fruquintinib, Anlotinib, etc.)
• Participated in clinical trials of other drugs within four weeks
• Urine routine examination indicated urine protein \> 2+, or 24-hour urine protein quantification ≥1.0g/24h
• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

anlotinib; penpulimab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Weijian Guo, M.D

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chenchen Wang, M.D

CONTACT

+8613774232040; wccnancy2003@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Medical Gastrointestinal Oncology

Model Details: Patients were first enrolled into cohort A, and when the efficacy of cohort A reached a certain percentage, the enrollment of cohort B started then.

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: February 8, 2022
• Study Start: March 9, 2022
• Primary Completion: May 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 3, 2024

Record last verified: 2024-07

Locations

CN (1)