Induction Chemotherapy Plus Chemoradiotherapy With or Without Aspirin in High Risk Rectal Cancer

NCT ID: NCT03170115

Last Updated: 2020-12-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-30
• Study Completion Date: 2020-01-17

Brief Summary

The benefit of aspirin in cancer of the colon and rectum is already known. Recently, it was described its potential activity during chemoradiotherapy, with higher rate of tumor downstaging. Furthermore, induction chemotherapy followed by chemoradiation represents an attractive approach, with more favorable compliance and toxicity profiles. The aim of this study was to evaluate the efficacy of total neoadjuvant treatment and assess the efficacy and feasibility of aspirin use during chemoradiotherapy for high-risk rectal cancer.

Detailed Description

Methods: This is a randomized trial to evaluate induction treatment with XELOX and Capecitabine-based chemoradiotherapy with or without aspirin in a high-risk population selected by MRI. High-risk will be defined by presence of at least one of the following criteria on high-resolution thin-slice MRI (3 mm): tumors extending to within 1 mm of, or beyond the mesorectal fascia; tumor extending 5 mm or more into perirectal fat; resectable cT4 tumors; lower third; nodal involvement; extramural vascular invasion. Random assignment of treatment will be stratified by MRI tumour regression grade. All the patients enrolled in the study will receive XELOX every 21 days for four cycles, unless unacceptable toxicity or progression is detected. After this treatment, patients will be randomized to receive Capecitabine-based chemoradiotherapy with aspirin or placebo (Capecitabine 850 mg/m² 5 days per week combined with radiotherapy with total dose of 50.4 Gy in 28 days). After 8-10 weeks, they will be evaluate by MRI. Patients with incomplete clinical response will be referred to immediate surgery and patients with complete clinical response will be managed with "watch and wait" approach. Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.

The sample size was calculated according to Simon's optimal two-stage design. Accordingly, 11 patients must be included in each group during the first stage and 20 during the second stage. A treatment regimen will be considered effective if more than 18 patients of the total 31 show downstaging (final analysis), reaching 80% power with an alpha of 0.05 level of significance.

Conditions

Rectal Cancer, Adenocarcinoma; Locally Advanced Malignant Neoplasm; Chemoradiation

Keywords

Rectal Cancer; Total neoadjuvant therapy; Induction chemotherapy; Aspirin colorectal cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Aspirin

Induction chemotherapy followed by chemoradiotherapy with aspirin Aspirin 100mg daily during the chemoradiotherapy

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

chemoradiotherapy with capecitabine and aspirin Aspirin daily during chemoradiotherapy

Placebo Oral Tablet

Induction chemotherapy followed by chemoradiotherapy without aspirin Placebo daily during the chemoradiotherapy

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

chemoradiotherapy with capecitabine and placebo Placebo daily during chemoradiotherapy

Interventions

Aspirin

chemoradiotherapy with capecitabine and aspirin Aspirin daily during chemoradiotherapy

Intervention Type: DRUG

Placebo Oral Tablet

chemoradiotherapy with capecitabine and placebo Placebo daily during chemoradiotherapy

Intervention Type: DRUG

Other Intervention Names

aas; placebo

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed adenocarcinoma of mid or low rectum

2. Locally advanced rectal cancer with one of the high-risk factors confirmed by high-resolution thin-slice Magnetic resonance image (3 mm)

• tumors extending to within 1 mm of, or beyond the mesorectal fascia;
• tumor extending 5 mm or more into perirectal fat;
• resectable cT4 tumors;
• lower third;
• nodal involvement;
• extramural vascular invasion

3. ECOG performance status of 0-2

4. An informed consent has been signed by the patient

Exclusion Criteria

1. Upper rectal cancer

2. Metastatic disease

3. The patient received any previous therapy for colorectal cancer or another malignancy

4. Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin

5. Previous thromboembolic or haemorrhagic events within 6 months prior to registration

6. Patients with malabsorption syndrome or difficulties in swallowing

7. The patient has severe underlying diseases or poor condition to receive chemotherapy or radiotherapy

8. Pregnant of breastfeeding women

9. The patient who participate in another clinical trial, or receives any drug for the trial

10. Uncontrolled peripheral neuropathy (more than grade 2)

11. Active gastrointestinal bleeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Nacional de Cancer, Brazil

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luiz Henrique Araujo, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, France

Locations

INCA- Instituto Nacional de Câncer

Rio de Janeiro, , Brazil

Countries

Brazil

Other Identifiers

ICAR trial

Identifier Type: -

Identifier Source: org_study_id