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

Primary Purpose

ColoRectal Cancer

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Irinotecan

Raltitrexed

About this trial

This is an interventional treatment trial for ColoRectal Cancer focused on measuring Raltitrexed, Irinotecan, Second-line Treatment, Advanced Colorectal Cancer(ACC)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

The First Hospital of China Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Irinotecan & Raltitrexed

Arm Description

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

Outcomes

Primary Outcome Measures

Progression Free Survival [PFS]

Secondary Outcome Measures

Overall Survival [OS]

Objective Response Rate [ORR]

Disease Control Rate [DCR]

Full Information

NCT ID

NCT03053167

First Posted

January 23, 2017

Last Updated

February 13, 2017

Sponsor

China Medical University, China

Collaborators

The First Affiliated Hospital of Dalian Medical University, The Second Affiliated Hospital of Dalian Medical University, Liaoning Tumor Hospital & Institute, Shengjing Hospital, General Hospital of Shenyang Military Region

1. Study Identification

Unique Protocol Identification Number

NCT03053167

Brief Title

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

Official Title

Irinotecan Plus Raltitrexed as Second-line Treatment in Advanced Colorectal Cancer Patients: An Open-label, Single-arm, Multicenter Phase II Study

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Unknown status

Study Start Date

December 2016 (undefined)

Primary Completion Date

December 2019 (Anticipated)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

China Medical University, China

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

ColoRectal Cancer

Keywords

Raltitrexed, Irinotecan, Second-line Treatment, Advanced Colorectal Cancer(ACC)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Irinotecan & Raltitrexed

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Other Intervention Name(s)

Campto

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Raltitrexed

Other Intervention Name(s)

Sai wei jian

Intervention Description

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

Primary Outcome Measure Information:

Title

Progression Free Survival [PFS]

Time Frame

5-6 months

Secondary Outcome Measure Information:

Title

Overall Survival [OS]

Time Frame

12-15 months

Title

Objective Response Rate [ORR]

Time Frame

12-15 months

Title

Disease Control Rate [DCR]

Time Frame

12-15 months

Other Pre-specified Outcome Measures:

Title

Incidence and Degree of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time Frame

12-15 months

Title

Performance Status [WHO-ECOG]

Time Frame

12-15 months

Title

Quality of Life [WHO-QOL]

Time Frame

12-15 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

YunPeng Liu, PhD

Phone

86-24-83282312

cmuliuyunpeng@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Zan Teng, PhD

Phone

86-024-83282542

tengzan@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

YunPeng Liu, PhD

Organizational Affiliation

First Hospital of China Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The First Hospital of China Medical University

City

Shenyang

State/Province

Liaoning

ZIP/Postal Code

110001

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yunpeng Liu, MD., PhD

Phone

86-24-83282312

cmuliuyunpeng@hotmail.com

First Name & Middle Initial & Last Name & Degree

Yunpeng Liu, MD., PhD.

12. IPD Sharing Statement

Citations:

PubMed Identifier

15865096

Citation

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.

Results Reference

result

PubMed Identifier

15083176

Citation

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.

Results Reference

result

PubMed Identifier

12187070

Citation

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.

Results Reference

result

PubMed Identifier

12196368

Citation

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.

Results Reference

result

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

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