Clinical trial NCT03142282: Consolidative Radiotherapy Plus Maintenance Chemotherapy for Metastatic Colorectal Cancer
Official title: Maintenance Chemotherapy Versus Consolidative Radiotherapy Plus Maintenance Chemotherapy for Unresectable Metastatic Colorectal Cancer: A Randomized Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Radiotherapy
Keywords: maintenance treatment
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2017-05-05
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Radiation: SBRT or IMRT Drug: Maintenance chemotherapy
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 2 years
Secondary outcomes:
measure: Actuarial rate in-field local control
timeFrame: 2 years
measure: Toxicities
timeFrame: 2 years
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China.
name: Tao Zhang, MD,PHD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.