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Short-course Radiotherapy With Induction and Consolidation Chemotherapy in Patients With Locally Advanced Rectal Cancer

Phase 2
Conditions
Rectal Cancer
Total Neoadjuvant Treatment
Interventions
Other: Approach
Registration Number
NCT04674696
Lead Sponsor
Instituto Nacional de Cancer, Brazil
Brief Summary

Short-course radiotherapy followed by consolidation chemotherapy has shown a better response rate when compared to chemoradiotherapy treatment.

In addition, recent studies have shown better tolerance with total neoadjuvant treatment, with induction or consolidation chemotherapy. Induction chemotherapy could reduce the size of the tumor, treat micrometastases early and allow treatment to start immediately (avoiding potential delays in waiting for radiotherapy). While consolidation chemotherapy allows longer waiting times for surgery, with higher response rates.

Detailed Description

Methods: This trial aim to evaluate induction treatment with CAPOX, followed by short-course radiotherapy consolidation chemotherapy with CAPOX. After 5-7 weeks, patients 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 Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.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, 21 patients must be included in each group during the first stage and 24 during the second stage. Treatment regimen will be considered effective if 9 or more patients show good response (final analysis), reaching 80% power with an alpha of 0.10 level of significance.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
54
Inclusion Criteria
  • Histologically confirmed adenocarcinoma of mid or low rectum
  • 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
  • ECOG performance status of 0-2
  • An informed consent has been signed by the patient
Exclusion Criteria
  • Upper rectal cancer
  • Metastatic disease
  • The patient received any previous therapy for colorectal cancer or another malignancy
  • Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
  • Previous thromboembolic or haemorrhagic events within 6 months prior to registration
  • Patients with malabsorption syndrome or difficulties in swallowing
  • The patient has severe underlying diseases or poor condition to receive chemotherapy or radiotherapy
  • Pregnant of breastfeeding women
  • The patient who participate in another clinical trial, or receives any drug for the trial
  • Uncontrolled peripheral neuropathy (more than grade 2)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ExperimentalApproachPatients will receive 2 CAPOX cycles, followed by short-course radiotherapy and 4 CAPOX cycles.
Primary Outcome Measures
NameTimeMethod
Evaluate MRI good response rate after the total neoadjuvant treatment16-20 weeks after SCRT

Good response rate is defined as the proportion of patients who reached mrTRG 1 or 2 and the absence of remote disease in the reevaluation period, with the denominator being the total number of patients who started total neoadjuvant treatment.

Secondary Outcome Measures
NameTimeMethod
Overall survival3 years

defined as the time from the date of the induction chemotherapy until the death or date of last contact

Disease-free survival in 3 years3 years

defined as the time from the date of MRI of the pelvis of the reassessment period to relapse, death or last contact date.

Describe the safety and tolerability of total neoadjuvant treatment.1 year

Incidence of adverse events (AEs), serious AEs, deaths and laboratory abnormalities in participants who received at least one dose of study treatment

Trial Locations

Locations (1)

INCA- Instituto Nacional de Câncer

🇧🇷

Rio de Janeiro, Brazil

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