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

NCT03634202 | Terminated

• 1 other identifier: ICO-A-2013-06
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer; Metastasis; Radiotherapy

Keywords

Intensity Modulated Radiotherapy; Simultaneous Integrated Boost; Low and middle Rectal carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Local Progression-free survival at 12 months,

  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

• To evaluate quality of Life

  84 months

• To evaluate quality of Life

  84 months

• Overall survival at 2 years

  24 months after inclusion

Study Arms (1)

IMRT + oral chemotherapy

EXPERIMENTAL

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

Interventions

IMRT + oral chemotherapy COMBINATION_PRODUCT

It's a dose escalation of radiation (IMRT), during 5 to 7 weeks, 5 days per week. Concomitantly, patient have oral chemotherapy (capecitabin)

Also known as: Intensity-Modulated Radiotherapy + capecitabine

IMRT + oral chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (1)

Institut de Cancérologie de l'Ouest

Angers, 49933, France

Location

MeSH Terms

Conditions

Rectal Neoplasms; Neoplasm Metastasis

Interventions

Radiotherapy, Intensity-Modulated; Drug Therapy; Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• AMAURY PAUMIER, MD

  Institut de Cancérologie de l'Ouest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase-1 study of escalade dose of radiation

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 16, 2018
• Study Start: May 5, 2015
• Primary Completion: December 10, 2018
• Study Completion: December 10, 2018
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)