Rechallenge of Prior Regimen in Third or Later-line Chemotherapy in Metastatic Colorectal Cancer

A Phase II Clinical Trial of Prior Regimen Rechallenge in Third or Later-line Chemotherapy for Patients With Metastatic Colorectal Cancer

This is a single-arm, open-label, single-center prospective phase II study to evaluate the efficacy and safety of rechallenge chemotherapy in the third or later-line treatment in patients with advanced colorectal cancer. The primary end point is progression free survival (PFS). A total of 42 patients who failed with oxaliplatin, irinotecan and fluorouracil in previous treatment and could not receive the target therapy presently are planned for recruitment. For patients with metastatic colorectal cancer who met admission criteria, oxaliplatin- or irinotecan-based chemo regimen could be used and evaluation was repeated every 6 weeks. The treatment continues until the disease progression or the untolerable adverse reaction.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer; Chemotherapy Effect
• Intervention / Treatment: Drug: the rechallenge regimen

Detailed Description

The treatment for reintroduction was oxaliplatin- or irinotecan-based chemo-regimen.

Optional chemotherapy regimen included XELOX,FOLFOX,FOLFIRI,Irinotecan single-agent

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Patients age between 18 and 80 years
2. Histologically confirmed metastatic colorectal cancer (mCRC)
3. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
4. Treatment failure to at least two lines of chemotherapy (regimens should include oxaliplatin, fluorouracil and irinotecan); progression free survival (PFS) of prior oxaliplatin or irinotecan-based chemotherapy should be at least four months without any unrecoverable toxicity. Prior target therapy was acceptable
5. For those who received other anti-tumor treatment, the toxicity should have been restored, with the time interval from last dose of cytotoxic drugs, radiation or surgery (the wound should be healed completely) ≥3 weeks
6. Life expectancy≥12 weeks
7. At least one measurable lesion as defined by RECIST 1.1
8. Acceptable hematologic, hepatic, and renal function within 7 days from screening: the blood ANC count≥1.5*10^9/L; hemoglobin≥9.0 g/dl, the blood platelet count≥80 x 10^9/L, total bilirubin<1.5*upper limits of normal(ULN), ALT and AST<2.5*ULN(< 5 *ULN for patients with live metastasis), endogenous creatinine clearance rate>50ml/min
9. Targeted drugs are currently not suitable or affordable

Exclusion Criteria

1. Receiving other systemic anti-cancer treatment within 3 weeks
2. Prior radiation therapy of target measurable lesion
3. Presence of Grade III or IV chemo-related toxicity in previous treatment without recovery to Grade II or less
4. With other malignant tumor in 5 years; except for cured cervical carcinoma in situ or basal cell carcinoma
5. Symptomatic intracranial or meningeal metastasis
6. History of uncontrolled seizures, central nervous system dysfunction or mental disorder
7. Uncontrolled pleural or peritoneal effusion
8. Severe life-threatening concomitant disease that might impair the safety of patients or affect the completion of treatment, according to the researcher's judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: The rechallenge regimens; XELOX ± BEV, repeating every 3 weeks. FOLFOX ± BEV, repeating every 2 week FOLFOX ± Cetuximab, repeating every 2 week FOLFIRI ± BEV, repeating every 2 weeks. FOLFIRI ± Cetuximab, repeating every 2 weeks. IRI ± BEV, repeating every 2 weeks. IRI ± Cetuximab, repeating every 2 weeks. Raltitrexed ± BEV, repeating every 3 weeks. Raltitrexed ± Cetuximab, repeating every 2 weeks.

Drug: the rechallenge regimen; XELOX regimen: Oxaliplatin 130mg/m2, intravenous, on day 1; Capecitabine 1000mg/m2, oral, twice daily, continuously for 14 days; ±bevacizumab 7.5mg/kg, intravenous, on day 1; repeating every 3 weeks. FOLFOX regimen: Oxaliplatin 85mg/m2 on day 1; Calcium folinate 400mg/m2 on day 1; 5-FU 400mg/m2 on day 1; 5-FU 2.4g/m2, continuous intravenous infusion for 46 hours, ± Bevacizumab 5mg/kg or ± Cetuximab 500mg/m2, repeating every 2 weeks. FOLFIRI regimen: Irinotecan 180mg/m2 on day 1; Calcium folinate 400mg/m2 on day 1; 5-FU 400mg/m2 on day 1; 5-FU 2.4g/m2, continuous intravenous infusion for 46 hours; ± Bevacizumab 5mg/kg or ± Cetuximab 500mg/m2, repeating every 2 weeks. Irinotecan monotherapy regimen: Irinotecan 180mg/m2 on day 1, ± Bevacizumab 5mg/kg or ± Cetuximab 500mg/m2, repeating every 2 weeks. Raltitrexed contained regimen: Raltitrexed 3mg/m2 on day 1; ± Bevacizumab 7.5mg/kg, repeating every 3 weeks; Raltitrexed 2mg/m2 on day 1; ± Cetuximab 500mg/m2, repeating every 2 weeks.; Other Names: reintroduction of the former regimens in the third or later line treatment even after the same treatment had shown drug-resistance in the former setting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	progression free survival	from the time signing of informed consent form(ICF) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	from the time signing of ICF until the date of death from any cause, assessed up to 48 months

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Henan Cancer Hospital
• Investigators: Principal Investigator: Weijian Guo, M.D, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Actual): December 24, 2022
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 3, 2023
• Last Verified: December 1, 2023

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
• Other Study ID Numbers: FDZL-RC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No