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

Phase-1 Study of Escalated-dose Pelvic Radiation Therapy Using Intensity-Modulated Radiotherapy (IMRT) With Simultaneous Integrated Boost (SIB), in Combination With Xeloda, for Initially Metastatic, Low and Middle Rectal Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Rectal Cancer; Metastasis; Radiotherapy
• Intervention / Treatment: Combination product: IMRT + oral chemotherapy

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • Institut de Cancérologie de l'Ouest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Combination product: IMRT + oral chemotherapy; It's a dose escalation of radiation (IMRT), during 5 to 7 weeks, 5 days per week. Concomitantly, patient have oral chemotherapy (capecitabin); Other Names: Intensity-Modulated Radiotherapy + capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	MTD = dose level -1 after at least 2 patients with DLT to upper level	84 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Progression-free survival at 12 months,	% patient with Local Progression at CT scan, 12 months after inclusion	12 months after inclusion
Toxicity profile of the chemoradiation step for NCI.CTC grade 3-4 local toxicities due to "Pelvic Radiation Disease"	% patient with >= grade 3 toxicity (NCI.CTC AE)	84 months
To evaluate quality of Life	EORTC-QLQC-30	84 months
To evaluate quality of Life	QLQ-CR29	84 months
Overall survival at 2 years	Overall survival is defined as the delay between the date of inclusion and the date of end of study	24 months after inclusion
The usefulness of surgery	The surgical decision within 12 months after the end of radiochemotherapy will be recovered	12 months after the end of radiochemotherapy
The prognostic value of PET	The interest of PET to define the volume in radiotherapy	108 months

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest
• Investigators: Principal Investigator: AMAURY PAUMIER, MD, Institut de Cancérologie de l'Ouest

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2015
• Primary Completion (Actual): December 10, 2018
• Study Completion (Actual): December 10, 2018

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 16, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Intensity Modulated Radiotherapy; Simultaneous Integrated Boost; Low and middle Rectal carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: ICO-A-2013-06

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