Consolidative Radiotherapy Plus Maintenance Chemotherapy for Metastatic Colorectal Cancer (MCRC-LC1)

Maintenance Chemotherapy Versus Consolidative Radiotherapy Plus Maintenance Chemotherapy for Unresectable Metastatic Colorectal Cancer: A Randomized Phase II Trial

This study is a randomized phase II trial of maintenance chemotherapy versus consolidative radiotherapy plus maintenance chemotherapy for patients with unresectable metastatic colorectal cancer (MCRC).

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer; Radiotherapy
• Intervention / Treatment: Drug: maintenance chemotherapy; Radiation: Consolidative Radiotherapy

Detailed Description

Prior to accrual on the trial, patients with unresectable metastatic colorectal cancer will be treated with palliative chemotherapy. And patients who achieve a partial response or stable disease by imaging criteria will receive maintenance chemotherapy. In our study, these group patients will be randomized to maintenance chemotherapy or consolidative radiotherapy to all sites of disease (followed by maintenance chemotherapy at the medical oncologist's discretion). Choices of palliative and maintenance chemotherapy will be determined by the medical oncologist based on clinical appropriateness.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tao Zhang, MD,PHD; Phone Number: 862785871982; Email: 1277577866@qq.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Tao Zhang, MD, PHD; Phone Number: 862785871982; Email: 1277577866@qq.com
      • Contact: Zhenyu Lin, MD; Phone Number: 15827130393; Email: tojilin@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have biopsy proven unresectable MCRC.
2. Patients must have received induction chemotherapy for 3-6 months, and achieved stable disease or a partial response.
3. Age ≥ 18 years
4. Patients must have measurable disease at baseline.
5. Patients can have up to only 5 discrete active extracranial lesions (≤3 in the liver and ≤3 in the lung) identified by position-emission tomography (PET) scan and also seen on correlative plain film, CT scan, or MRI within 8 weeks prior to the initiation of radiotherapy.
6. Patients who previously received radiotherapy to the primary site will be ineligible if there is CT evidence of disease progression within the past 3 months.
7. Patients must have a Karnofsky Performance Scores (KPS) >60
8. Aspartate aminotransferase, alanine aminotransferase & Alkaline phosphates must be ≤ 2.5 times the upper limit of normal (ULN). Total bilirubin must be within the limit of normal.
9. Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm³.
10. Patients should have adequate renal function (serum creatinine ≤1.5 times the ULN).
11. Females of childbearing potential should have a negative pregnancy test.
12. Patients who would be receiving radiation for lung lesions who are known or suspected by the treating radiation oncologist to have compromised lung function must have a documented forced expiratory volume in 1 second (FEV1) ≥ 1 litre.
13. Patients must provide verbal and written informed consent to participate in the study.
14. Total bilirubin: within normal institutional limits

Exclusion Criteria:

1. Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible
2. Patients with serious, uncontrolled, concurrent infection(s).
3. Significant weight loss (>10%) in the prior 3 months.
4. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cancers.
5. Patients with more than 5 discrete metastatic lesions.
6. Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
7. Unwillingness to participate or inability to comply with the protocol for the duration of the study.
8. Patients who are pregnant. Patients with reproductive capability will need to use adequate contraception during the time of participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Maintenance chemotherapy; FDA approved drugs for the study population: Bevacizumab, Xeloda	Drug: maintenance chemotherapy; National Comprehensive Cancer Network (NCCN) or European Society for Medical Oncology (ESMO) suggested maintenance chemotherapy regimens: xeloda, bevacizumab
Experimental: Radiotherapy; consolidative radiotherapy plus maintenance chemotherapy	Radiation: Consolidative Radiotherapy; Stereotacticbodyradiationtherapy (SBRT) or intensity modulated radiation therapy (IMRT) for metastatic sites (less than 5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Evaluate the effect of consolidative radiotherapy with or without maintenance chemotherapy versus maintenance chemotherapy alone on progression free survival	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicities	Acute toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 criteria during and up to 3 months after radiotherapy. Late toxicity was graded using the Radiation Therapy Oncology Group (RTOG)/European Organisation for the Research and Treatment of Cancer (EORTC) criteria.	2 years
Actuarial rate in-field local control	To describe the actuarial rate in-field local control and rate of out-of-field disease progression	2 years
Overall survival	To evaluate overall survival after consolidative radiotherapy followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.	5 years

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Study Chair: Tao Zhang, MD,PHD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China.

Publications and helpful links

General Publications

• Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.
• Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): August 31, 2021
• Study Completion (Anticipated): August 31, 2024

Study Registration Dates

• First Submitted: April 26, 2017
• First Submitted That Met QC Criteria: May 2, 2017
• First Posted (Actual): May 5, 2017

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: September 5, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: maintenance treatment
• 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: MCRC-LC1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No