Study of Radiation Therapy in Combination With Xeloda, for Initially Metastatic, Low and Middle Rectal Cancer

Not Applicable

Terminated

• Conditions: Radiotherapy; Rectal Cancer; Metastasis
• Interventions: Combination Product: IMRT + oral chemotherapy

• Registration Number: NCT03634202
• Lead Sponsor: Institut Cancerologie de l'Ouest

Brief Summary

In initially metastatic rectal carcinoma, a neo-adjuvant multi-drug chemotherapy is usually performed, followed by a pelvic chemoradiation. The surgical indications on both metastases and the pelvic site are then discussed: in the case where a complete (or near-complete) response (CR) of the rectal tumor is observed (10 to 40%), the local surgery may be omitted or poned ("wait-and-see") in a sphincter-sparing strategy, in order to minimize or avoid the surgical morbidity, to focus on metastatic disease by the continuation of chemotherapy, and to preserve a better quality of life. After 8 weeks of induction chemotherapy (mFolfox6 regimen, 4 cycles), the aim of our study is to optimize the chemoradiation step on the distal rectal tumor, thanks to Intensity-Modulated Radiotherapy (IMRT) with simultaneous integrated boost (SIB) (Phase-1 part of the study), concomitantly with oral capecitabine. According to a Fibonacci dose-escalation scheme, 3 radiation dose-levels are defined, up to the definition of the maximal tolerated dose (MTD), requiring the inclusion of a maximum of 20 patients. Further patients will be included at the recommended dose for phase-2 (RDP2) in a two-step phase-2 study, considering simultaneously as principal objective at 12 months, both the efficacy (local CR rate in the range of 10 to 25%) and the tolerance (pelvic radiation disease: grade 3-4 toxicities in the range of 30 to 10%). Overall 65 patients will be included in the phase-2 study at the RDP2 dose.

Detailed Description

The study population has metastatic rectal cancer. After obtaining informed consent and if they fulfil all of the criteria for inclusion, patients will be included.

After 8 weeks of induction chemotherapy with FOLFOX, patients perform an imaging assessment.

Then they are treated by radiotherapy with an oral Xeloda At the end of irradiation, patients realize on other Imaging assessment. Patients are then followed for 2 years

Study Timeline

• Study Start: 2015-05-05
• Study First Submitted: 2018-08-06
• Study First Submitted QC: 2018-08-14
• Study First Posted: 2018-08-16
• Primary Completion: 2018-12-10
• Study Completion: 2018-12-10
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-13
• Last Update Posted: 2019-05-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. Metastatic distal rectal carcinoma (low and middle);
2. age >18 years
3. Estimated life expectancy greater than 3 months
4. PS: ECOG<2
5. Normal hematologic, renal and hepatic functions
6. Normal or only partially decreased DPD activity
7. Effective contraception in women and men of childbearing age
8. Social insurance.
9. Signed informed consent

Exclusion Criteria

1. No previous treatment with pelvic radiotherapy or chemotherapy
2. Disorder precluding understanding of trial information or informed consent
3. No severe or uncontrolled disease (infection, VIH, HBs, diabetes mellitus)
4. No peripheral neuropathy > grade 2
5. No inflammatory disease or fructosemia
6. Diarrhea of grade > 2
7. Pregnancy, breastfeeding women
8. Patients already included in another therapeutic within a period of 30 days
9. Other malignancy treated within the last 5 years (except non-melanoma skin cancer)
10. Bilateral total hip prosthesis
11. Patient is willing and able to comply with the protocol for the duration of the study including all scheduled treatment, visits and examinations

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMRT + oral chemotherapy	IMRT + oral chemotherapy	Radiotherapy = IMRT with SIB. The overall duration of irradiation is 5 to 7 weeks Chemotherapy = oral capecitabine. Chemotherapy is taken in concomitance as radiotherapy days

Primary Outcome Measures

Name	Time	Method
maximum tolerated radiation dose (MTD) delivered by IMRT with SIB, in combination with oral capecitabine, for initially metastatic, low and middle rectal cancer after 4 induction cycles of mFolfox6 regimen.	84 months	MTD = dose level -1 after at least 2 patients with DLT to upper level

Secondary Outcome Measures

Name	Time	Method
The prognostic value of PET	108 months	The interest of PET to define the volume in radiotherapy
Local Progression-free survival at 12 months,	12 months after inclusion	% patient with Local Progression at CT scan, 12 months after inclusion
Toxicity profile of the chemoradiation step for NCI.CTC grade 3-4 local toxicities due to "Pelvic Radiation Disease"	84 months	% patient with \>= grade 3 toxicity (NCI.CTC AE)
To evaluate quality of Life	84 months	QLQ-CR29
Overall survival at 2 years	24 months after inclusion	Overall survival is defined as the delay between the date of inclusion and the date of end of study
The usefulness of surgery	12 months after the end of radiochemotherapy	The surgical decision within 12 months after the end of radiochemotherapy will be recovered

Trial Locations

Locations (1)

Institut de Cancérologie de l'Ouest; 🇫🇷 Angers, France