Clinical trial NCT03634202: Study of Radiation Therapy in Combination With Xeloda, for Initially Metastatic, Low and Middle Rectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Rectal Cancer
Metastasis
Radiotherapy
Keywords: Intensity Modulated Radiotherapy
Simultaneous Integrated Boost
Low and middle Rectal carcinoma
Lead sponsor: Institut Cancerologie de l'Ouest
Sponsor class: OTHER
First posted: 2018-08-16
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase-1 study of escalade dose of radiation
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 84 months
Secondary outcomes:
measure: Local Progression-free survival at 12 months,
timeFrame: 12 months after inclusion
measure: Toxicity profile of the chemoradiation step for NCI.CTC grade 3-4 local toxicities due to "Pelvic Radiation Disease"
timeFrame: 84 months
measure: To evaluate quality of Life
timeFrame: 84 months
measure: To evaluate quality of Life
timeFrame: 84 months
measure: Overall survival at 2 years
timeFrame: 24 months after inclusion
measure: The usefulness of surgery
timeFrame: 12 months after the end of radiochemotherapy
measure: The prognostic value of PET
timeFrame: 108 months
Other outcomes:
Locations:
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest
Study officials:
affiliation: Institut de Cancérologie de l'Ouest
name: AMAURY PAUMIER, MD
role: PRINCIPAL_INVESTIGATOR
References: