Combined Use of Raltitrexed and S-1 as Treatment for Patients With Metastasizing Colorectal Cancer

A Phase II Clinical Study of Combined Use of Raltitrexed and S-1 as Treatment for Patients With Metastasizing Colorectal Cancer Failed of Standard Chemotherapy

The primary endpoint is to evaluate the Median disease progression free survival (mPFS).

Study Overview

• Status: Unknown
• Conditions: Metastatic Colon Cancer
• Intervention / Treatment: Drug: Raltitrexed and S-1

Detailed Description

The primary endpoint is to evaluate the disease progression free survival (mPFS) of Raltitrexed combined with S-1 as treatment for patients with metastasizing colorectal cancer failed of standard chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • ShangHai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥18 years of age
2. Histologically or cytologically confirmed adenocarcinoma of the colon or rectum 3. No systemic chemotherapy for metastatic tumors

4. ECOG (Eastern Cooperative Oncology Group) 0-1 and expected survival period for 3 months or more 5. At least one measurable objective tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 6. ANC≥1.5*109/L；PLT≥80*109/L；HB≥90g/L；Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) ; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)；ALB ≥ 30g/L; Serum creatinine ≤1.5(ULN) or glomerular filtration rate (GFR) ≥60 ml/min screening within 7 days 7. Progression during or within 3 months following the last administration of approved standard therapies which must include a fluoropyrimidine, oxaliplatin and irinotecan. Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy. Subjects who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated with oxaliplatin-based therapy to be eligible. Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed into the study. Subjects may have received prior treatment with Avastin (bevacizumab) and/or Erbitux (cetuximab)/Vectibix (panitumumab) (if KRAS WT) 8. Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.

Exclusion Criteria:

1. Prior treatment with raltitrexed and gimeracil and oteracil potassium
2. Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy and hormonal therapy during this trial or within 4 weeks (or 6 weeks for mitomycin C) before starting to receive study medication.
3. Alcohol or drug addictions
4. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]
5. Any history of or currently known brain metastases
6. Multiple primary colorectal carcinoma
7. Concomitant participation or participation within the last 30 days in another clinical trial
8. There is an important organ failure or other serious diseases, including coronary artery disease, symptomatic cardiovascular disease or myocardial infarction within 12 months; serious neurological or psychiatric history; severe infection; actively disseminated vascula blood coagulation.
9. Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
10. Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
11. Pleural effusion or ascites that causes respiratory compromise (≥Common Terminology Criteria for Adverse Events [CTCAE]) Grade 2 dyspnea)
12. Subjects unable to swallow oral medications
13. Known history of human immunodeficiency virus (HIV) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: combined use Raltitrexed and S-1; Raltitrexed 3mg/m2 intravenously guttae, d1 and S-1,bid,po,d1-d14,every three weeks for a cycle. BSA(body surface area) S-1 dosage <1.25 m2 80 mg/d; 1.25m2 - <1.5 m2 100 mg/d; 1.5 m2 120 mg/d	Drug: Raltitrexed and S-1; Raltitrexed 3mg/m2 intravenously guttae, d1 and S-1,bid,po,d1-d14,every three weeks for a cycle. BSA (body surface area) S-1 dosage <1.25 m2 80 mg/d; 1.25m2 - <1.5 m2 100 mg/d; 1.5 m2 120 mg/d; Other Names: Tomudex, Gimeracil and oteracil porassium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Median disease progression free survival (mPFS) of Raltitrexed combined with S-1	at least 24 months

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Study Chair: Wei Jian Guo, doctor, Fudan University

Publications and helpful links

General Publications

• Huang M, Yang Y, Zhu X, Chen Z, Zhang W, Wang C, Zhang X, Qiu L, Zhang Z, Zhao X, Li W, Wang Y, Guo W. A prospective phase II study of raltitrexed combined with S-1 as salvage treatment for patients with refractory metastatic colorectal cancer. Asia Pac J Clin Oncol. 2021 Dec;17(6):513-521. doi: 10.1111/ajco.13511. Epub 2021 Feb 10.

Study record dates

Study Major Dates

• Study Start: December 25, 2015
• Primary Completion (ANTICIPATED): November 1, 2017
• Study Completion (ANTICIPATED): November 1, 2017

Study Registration Dates

• First Submitted: November 17, 2015
• First Submitted That Met QC Criteria: November 28, 2015
• First Posted (ESTIMATE): December 1, 2015

Study Record Updates

• Last Update Posted (ACTUAL): October 2, 2017
• Last Update Submitted That Met QC Criteria: September 29, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Folic Acid Antagonists; Raltitrexed
• Other Study ID Numbers: guoweijian-2015-RS