Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly

September 1, 2021 updated by: Jing Jin, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Multicenter, Phase II Study of Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly

The aim of this multicenter phase II study is to evaluate the response rate, local control, disease-free survival and treatment-related toxicity of preoperative chemoradiation for intermediate or locally advanced rectal cancer in the fit elderly.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The concurrent chemoradiotherapy has become the standard treatment for patients with intermediate or locally advanced rectal cancer. However, the data from prospective trial for elderly patients is still lacking.

The aim of this multicenter phase II study is to evaluate the response rate, local control, disease-free survival and treatment-related toxicity of preoperative chemoradiation with Raltitrexed for intermediate or locally advanced rectal cancer in the fit elderly aged 70 years above.

And all the participants have to be evaluated by comprehensive geriatric assessment (CGA). Clinical stage was evaluated by chest and abdominal computed tomography, endorectal ultrasound, and/or pelvic magnetic resonance imaging.

5 weeks after the preCRT, the multi-disciplinary team decided the following treatment of patients based on imaging evaluation. Surgical resection would be done with a minimum interval of 6 weeks after the last radiation. Acute toxicity was evaluated during and within 2 weeks after CRT. Toxicities were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

Sample size consideration.It has been calculated that 68 patients will need to be included, according to the following assumptions:

Recruitment period of 24 months. Minimum follow-up period of 24 months. We estimated that 51 patients were required to test the hypothesis that the 2-year DFS was equal to or greater than 78% with 80% power and to reject the hypothesis that the 2-year DFS rate was less than 63% at a significance level of 5% (one sided).Taking into account that a 5% percentage of losses, 20% of patients will refuse surgery, 68 patients are expected to be included in the study.

The interim analysis design. An interim safety evaluation will be carried out when 39 patients have finished their preoperative CRT. As the tolerance of elderly patients for nonhematological toxicities (such as diarrhoea) was often more poor than hematological toxicities, we estimated that 39 patients were required to test the hypothesis that the nonhematological G3 or higher acute toxicities rate was equal to or less than 21% ( safety result of patients aged 70 years or older from ACCOR12/PRODIGE 2 phase III trial) with 80% power and to reject the hypothesis that the rate was more than 36% at a significance level of 10% (one sided). If nonhematological G3 or higher acute toxicites is observed in12 or more patients, the H0 hypothesis will be rejected, and the protocal should be re-evaluated.

Biospecimen Retention. Blood, plasma, feces and tissue (optional). Feces were collected before any treatment. Peripheral blood samples of 10-20mL were collected from the patients for CTCs analysis, exploration analysis for frailty and tumor marker before and after preCRT, before and after surgery, and then on each follow up visit, according to our study protocal.

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100021
        • Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

71 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • Inclusion Criteria:

    • Rectal adenocarcinoma, clinical stage II/III(T3-4 or N+, AJCC 7th), and fulfils the intermediate or locally advanced risk category standard of ESMO recal cancer clinical practice guidelines 2013.
    • KPS status no less than 70; Charlson comorbidity no more than 2; Fit status evaluated by CGA.
    • Life expectancy more than 6 months.
    • Hemoglobin >= 100g/L, white blood cell >= 3.5*10E9/L, neutrophil >= 1.5*10E9/L, platelet >= 100*10E9/L.
    • Creatin normal, Total bilirubin normal, AST and AST normal, AKP normal.
    • Do not receive surgery ( except palliative colostomy) or chemotherapy or other anti-cancer treatment.
    • No previously pelvic irradiation history.
    • Through MDT discussion, the patient is considered to be candidate for preoperative CRT followed by surgery.
    • Informed consent signed.

  • Exclusion Criteria:

    • Other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma.
    • Allergy history to analog of quinazoline folate.
    • Active infection existed.
    • Severe complication, such as acute myocardial infarction in 6 months, uncontrolled diabetes ( Plasma glucose concentrations in any time of a day≥11.1mmol/L）, severe cardiac arrhythmia, etc.
    • Anticipate other clinical trials in four weeks before enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: preCRT+surgery
Treatment including preoperative chemoradiotherapy (preoperative radiation with concurrent chemotherapy) with Raltitrexed followed by surgery. Radiotherapy will be delivered to a planning target volume with a dose of 45-50.4Gy (1.8-2.0Gy daily) using with Intensity-Modulated Radiotherapy or Volumetric-Modulated Arc Therapy technique. During the radiation treatment, concurrent chemotherapy will be delivered (Raltitrexed, intravenous infusion, 3 mg/m2, on d1 and d22). Pelvic surgery is planned 6 weeks after completion of CRT based on the decision of MDT.
Drug: Raltitrexed
concurrent chemotherapy
Other Names:
  • Raltitrexed Injection
Radiation: Preoperative radiation
Radiation treatment before surgery
Other Names:
  • Preoperative radiotherapy
Procedure: Pelvic surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year disease-free survival probability (%)
Time Frame: 2 year
The probability of staying free from recurrence at 2 year after surgery or clinical complete response of tumor validated on imaging or pathological examination.
2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5-year overall survival probability
Time Frame: 5 year
The probability of staying alive at 5 year after surgery or end of CRT (for those who did not receive surgery).
5 year
5-year cancer-specific survival probability
Time Frame: 5 year
The probability of staying free from death caused by cancer at 5 year after surgery or end of CRT (for those who did not receive surgery).
5 year
The ratio of patients occured pCR
Time Frame: 2 weeks after surgery
The ratio of patients occured pathological complete response of tumor.
2 weeks after surgery
The ratio of patients occured Grade 3 or higher adverse events.
Time Frame: During chemoradiotherapy and within 180 days after surgery
During chemoradiotherapy and within 180 days after surgery
QOL
Time Frame: Before and after chemoradiotherapy and surgery, and then follow up for 3 years
The quality of life assessment score by EORTC QLQ-C30 and EORTC QLQ-CR29.
Before and after chemoradiotherapy and surgery, and then follow up for 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory endpoints
Time Frame: 5 years
To investigate the biomarker from blood or feces (such as circulating tumor cells, circulating tumor DNA) for treatment response and prognosis predicting. To investigate the CGA elements, and willingness evaluation to surgery for predicting the adherence, tolerence and prognosis of patients.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Investigators

  • Principal Investigator: Jing Jin, MD, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

May 1, 2021

Study Completion (Actual)

August 1, 2021

Study Registration Dates

First Submitted

November 30, 2016

First Submitted That Met QC Criteria

December 13, 2016

First Posted (Estimate)

December 14, 2016

Study Record Updates

Last Update Posted (Actual)

September 9, 2021

Last Update Submitted That Met QC Criteria

September 1, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CH-GI-098

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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