Clinical trial NCT04864067: No Operation After Short Course Radiotherapy Followed By Consolidation Chemotherapy In Locally Advanced Rectal Cancer
Official title: No Operation After Short Course Equivalent Dose (Ht) Radiation Therapy Followed By Consolidation Chemotherapy In Locally Advanced Rectal Cancer: The Prospective, Single Arm NOAHS-ARC Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Rectal Cancer
Radiotherapy
Neoadjuvant therapy
Adenocarcinoma
Lead sponsor: Servicio de Salud Metropolitano Sur Oriente
Sponsor class: OTHER_GOV
First posted: 2021-04-28
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to explore the hypothesis that in patients with a Locally advanced rectal cancer (LARC) treated with a Total neoadjuvant therapy (TNT) strategy based on short course radiotherapy (5x5Gy) followed by neoadjuvant consolidation chemotherapy is associated with a higher rate of pathological clinical response and sustained (\>1year) complete clinical response when compared to an historical cohort treated with long course chemoradiation therapy (CRT), total mesorectal excision (TME) and adjuvant chemotherapy (ACT).

Detailed description: Non-operative management with a Watch and Wait (W\&W) strategy has been advocated for selected patients with a locally advanced rectal cancer (LARC) and a complete clinical response (cCR) after neoajuvant (NA) treatment.

In this context, total neoadjuvant therapy (TNT), i.e the use of radiotherapy and full dose of post-operative chemotherapy as part of NA treatment, has emerged as a strategy to enhance treatment response.

Currently, TNT has reported higher rates of pCR and organ preservation when compared to current standard of care. However, the best TNT strategy is still unknown. We therefore hypothesize that in LARC patients, the use of a TNT strategy based on short course RT followed by consolidation chemotherapy is associated with a higher rate of pCR and sustained (\>1year) cCR when compared to an historic cohort.

The main aim of the present proposal is to assess the effects of a standardized TNT model in LARC patients as a strategy for enhanced pCR/sustained cCR. For this purpose, we propose the following experimental model: In primary Aim 1 we will study if the effects of a TNT strategy over patients with a LARC enhance the rate of pCR/sustained cCR by (1) evaluating the compliance and toxicity of a TNT strategy as a proof of concept of its applicability, (2) assessing the rate of cCR at the end of TNT and (3) assessing the rate of pCR in the surgically managed subgroup and sustained cCR (\>1year) in the W\&W subgroup. Additionally, in primary Aim 2, we will determine if patients with a W\&W strategy have better functional outcomes and quality of life (QoL) than patients treated with TME after TNT by (1) using validated questionnaires for the evaluation of bowel, sexual and urinary function for W\&W and TME patients and (2) by evaluating the QoL using a widely-used standardized questionnaire.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of adenocarcinoma of the rectum
* Clinical Stage II (T3-4, N-) or Stage III (any T, N+) based on Magnetic Resonance Imaging (MRI)
* Tumors \< 7cm from anal verge (palpable)
* No prior history of rectal cancer

Exclusion Criteria

* Patients with tumors \>7cm from anal verge
* ECOG \>1,
* Contraindication for chemotherapy: Hemoglobin \<8, White Blood Count \<4000, Platelets \<100,000, Creatinine Clearance \<50ml/min, Total Bilirubin \<5mg/dl,
* Stage IV at diagnosis
* Coronary artery disease, either no treated or recent acute coronary syndrome in the last 12 months.
* Congestive heart failure
* Peripheral neuropathy
* Previous pelvic radiotherapy
* Prior rectal cancer treatment
* Pregnancy or nursery
* Any contraindications to MRI (e.g. patients with pacemakers)
* Indication of pelvic exenteration
* Impossibility to consent.

Primary outcomes:
measure: Rate of pathological and sustained clinical response
timeFrame: 3 years
measure: Quality of Life and Funcional Outcomes
timeFrame: 3 years
Secondary outcomes:
measure: Adverse events
timeFrame: 3 years
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Complejo Asistencial Doctor Sótero del Rio
state: RM
city: Santiago
country: Chile
facility: Hospital La Florida
state: RM
city: Santiago
country: Chile
facility: Hospital Padre Hurtado
state: RM
Study officials:
affiliation: Complejo Asistencial Doctor Sótero del Rio
name: Felipe F Quezada-Diaz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Asistencial Doctor Sótero Del Río
name: Nicole M Caire, MD
role: PRINCIPAL_INVESTIGATOR
References: