Irinotecan Plus Raltitrexed as Second-line Treatment in Advanced Colorectal Cancer Patients

NCT ID: NCT03053167

Last Updated: 2017-02-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2020-12-31

Brief Summary

Irinotecan and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. The purpose of this study is to evaluate efficacy and safety of irinotecan plus raltitrexed as second-line treatment in advanced colorectal cancer patients.

Detailed Description

The standard initial treatment for patients with advanced colorectal cancer (ACC) not amenable for surgical resection is palliative 5-fluorouracil (5-FU)-based chemotherapy. However, response rates are low and prognosis remains poor, with median survival times about one year. Until recently, second-line therapy options were limited.

Irinotecan is a semisynthetic camptothecin derivate that acts as a DNA-topoisomerase-1 inhibitor,its most frequent toxic effects are diarrhea, neutropenia and cholinergic syndrome. Raltitrexed is a quinazoline folate-based specific thymidylate synthase inhibitor, its clinical activity in this setting is similar to that of modulated 5-FU regimens but with a better toxicity profile (mainly asthenia and increased serum transaminase levels). There seems to be no cross-resistance between 5-FU and raltitrexed. Irinotecan and raltitrexed have different toxicity profiles and modes of action. Both drugs are active as single agents and may be given as a short 3-weekly infusion, thus obviating complex schedules or the need for implantable venous access devices. Preclinical studies have demonstrated a pronounced sequence-dependent synergy between SN-38 (the active metabolite of irinotecan) and raltitrexed. It seems then interesting to explore the feasibility and therapeutic potential of this association.

With this background, the investigators have performed this study to evaluate efficacy and safety of irinotecan plus raltitrexed as second-line treatment in advanced colorectal cancer patients.

Conditions

ColoRectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Irinotecan & Raltitrexed

advanced colorectal cancer patients treated with irinotecan plus raltitrexed as second-line treatment.

Irinotecan:180mg/㎡+NS250ml, ivgtt, 90min, d1

Raltitrexed: 3mg/㎡+NS100ml，ivgtt，15min, d1 Every 3 weeks

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

Irinotecan: 180mg/㎡+NS250ml, ivgtt, 90min, d1 Every 3 weeks

Raltitrexed

Intervention Type: DRUG

Raltitrexed: 3mg/㎡+NS100ml，ivgtt，15min, d1 Every 3 weeks

Interventions

Irinotecan

Irinotecan: 180mg/㎡+NS250ml, ivgtt, 90min, d1 Every 3 weeks

Intervention Type: DRUG

Raltitrexed

Raltitrexed: 3mg/㎡+NS100ml，ivgtt，15min, d1 Every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Campto; Sai wei jian

Eligibility Criteria

Inclusion Criteria

• life expectancy of at least 3 months;
• histological and/or cytological confirmation of ACC;
• disease progression while on first-line palliative oxaliplatin & fluoropyrimidine chemotherapy or relapse within 6 months after adjuvant oxaliplatin & fluoropyrimidine chemotherapy;
• wash-out time of 4 weeks after the last chemotherapy infusion or radiotherapy，and observed lesions not in the radiotherapy target；
• at least one measurable objective tumor lesion by spiral CT examination, the maximum diameter ≥ 1cm（according to RECIST 1.1）；
• ECOG performance status 0-1；
• satisfactory main organ function，laboratory test must meet the following criteria: hemoglobin (HGB) ≥90g/L, neutrophil count（ANC） ≥1.5×109/L, platelet count（PLT） ≥90×109/L, Serum creatinine（CR）≤1.5 upper normal limitation (UNL)，creatinine clearance rate (CCr) ≥60ml/min, total bilirubin (TBil) ≤1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 UNL (For patients with liver metastasis, the AST/ALT must be ≤5.0 UNL);
• For women with child bearing potential, a negative serum or urine pregnancy test result should be obtained before enrollment
• written informed consent.

Exclusion Criteria

• prior exposure to irinotecan or raltitrexed;
• chronic enteropathy on unresolved bowel obstruction;
• Pregnant or lactated women;
• previous malignant disease other than carcinoma in situ of the cervix or basal cell carcinoma of the skin;
• Concurrent administration of any other investigational drug, or have been enrolled in other clinical trial with investigational drug treatment within the 30 days of start of study treatment；
• cerebral metastases or leptomeningeal carcinomatosis;
• severe or uncompensated concomitant medical conditions.
• Unsuitable for the study or other chemotherapy determined by investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Dalian Medical University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Dalian Medical University

OTHER

Sponsor Role: collaborator

Liaoning Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Shengjing Hospital

OTHER

Sponsor Role: collaborator

General Hospital of Shenyang Military Region

OTHER

Sponsor Role: collaborator

China Medical University, China

OTHER

Sponsor Role: lead

Responsible Party

Yunpeng Liu

Director of Department of Medical Oncology，The First Hospital of China Medical University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

YunPeng Liu, PhD

Role: PRINCIPAL_INVESTIGATOR

First Hospital of China Medical University

Locations

The First Hospital of China Medical University

Shenyang, Liaoning, China

Site Status: RECRUITING

Countries

China

Central Contacts

YunPeng Liu, PhD

Role: CONTACT

cmuliuyunpeng@hotmail.com

86-24-83282312

Zan Teng, PhD

Role: CONTACT

tengzan@163.com

86-024-83282542

Facility Contacts

Yunpeng Liu, MD., PhD

Role: primary

cmuliuyunpeng@hotmail.com

86-24-83282312

References

Chiara S, Nobile MT, Tomasello L, Acquati M, Taveggia P, Murolo C, Percivale P, Rosso R. Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer. Anticancer Res. 2005 Mar-Apr;25(2B):1391-6.

Reference Type: RESULT

PMID: 15865096 (View on PubMed)

Feliu J, Salud A, Escudero P, Lopez-Gomez L, Pericay C, Castanon C, de Tejada MR, Rodriguez-Garcia JM, Martinez MP, Martin MS, Sanchez JJ, Baron MG; Oncopaz Cooperative Group and Associated Hospitals. Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study. Br J Cancer. 2004 Apr 19;90(8):1502-7. doi: 10.1038/sj.bjc.6601713.

Reference Type: RESULT

PMID: 15083176 (View on PubMed)

Aparicio J, de las Penas R, Vicent JM, Garcera S, Llorca C, Maestu I, Yuste AL, Farres J. Multicenter phase I study of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer. Oncology. 2002;63(1):42-7. doi: 10.1159/000065719.

Reference Type: RESULT

PMID: 12187070 (View on PubMed)

Carnaghi C, Rimassa L, Garassino I, Zucali PA, Masci G, Fallini M, Morenghi E, Santoro A. Irinotecan and raltitrexed: an active combination in advanced colorectal cancer. Ann Oncol. 2002 Sep;13(9):1424-9. doi: 10.1093/annonc/mdf229.

Reference Type: RESULT

PMID: 12196368 (View on PubMed)

Cheng Y, Teng Z, Zhang Y, Jin B, Zheng Z, Man L, Wang Z, Teng Y, Yu P, Shi J, Luo Y, Wang Y, Zhang J, Zhang H, Liu J, Chen H, Xiao J, Zhao L, Zhang L, Jiang Y, Chen Y, Zhang J, Wang C, Liu S, Qu J, Qu X, Liu Y. Irinotecan plus raltitrexed as second-line treatment in locally advanced or metastatic colorectal cancer patients: a prospective open-label, single-arm, multi-center, phase II study. BMC Cancer. 2024 Sep 2;24(1):1082. doi: 10.1186/s12885-024-12831-4.

Reference Type: DERIVED

PMID: 39223545 (View on PubMed)

Other Identifiers

CLOG1602

Identifier Type: -

Identifier Source: org_study_id