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

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ClinicalTrials.gov Identifier: NCT03170115
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : February 28, 2018
Sponsor:
Information provided by (Responsible Party):
Instituto Nacional de Cancer, Brazil

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.

Condition or disease Intervention/treatment Phase
Rectal Cancer, Adenocarcinoma Locally Advanced Malignant Neoplasm Chemoradiation Drug: Aspirin Drug: Placebo Oral Tablet Phase 2

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 Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: preoperative induction chemotherapy followed by combined radiochemotherapy with capecitabine and aspirin
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II Randomized Study of Induction Chemotherapy Followed by Chemoradiotherapy With or Without Aspirin in High Risk Locally Advanced Rectal Cancer
Actual Study Start Date : November 30, 2017
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Aspirin
Induction chemotherapy followed by chemoradiotherapy with aspirin Aspirin 100mg daily during the chemoradiotherapy
Drug: Aspirin
chemoradiotherapy with capecitabine and aspirin Aspirin daily during chemoradiotherapy
Other Name: aas

Placebo Comparator: Placebo Oral Tablet
Induction chemotherapy followed by chemoradiotherapy without aspirin Placebo daily during the chemoradiotherapy
Drug: Placebo Oral Tablet
chemoradiotherapy with capecitabine and placebo Placebo daily during chemoradiotherapy
Other Name: placebo




Primary Outcome Measures :
  1. Tumor downstaging after induction chemotherapy followed by chemoradiotherapy with or without aspirin [ Time Frame: 8-10 weeks after chemoradiotherapy ]
    This will be assessed by MR imaging 8-10 weeks after chemoradiotherapy and it will be considered tumor downstaging if mrTRG 1 to 3


Secondary Outcome Measures :
  1. Radiological Tumor response rate after induction chemotherapy [ Time Frame: 3-4 weeks after last induction chemotherapy ]
    This will be assessed by MR imaging after induction chemotherapy

  2. Pathological Tumor response rate [ Time Frame: 10-12 weeks after chemoradiotherapy ]
    Amount of tumor regression after surgery according to the guideline including Mandard

  3. Pathologic complete response [ Time Frame: 8-10 weeks after chemoradiotherapy ]
    it will be defined as the absence of residual invasive cancer on pathological evaluation of the complete resected rectal specimen

  4. Disease-free survival [ Time Frame: 3 years ]
    defined as the time from surgery to relapse or death, whichever occurred first

  5. Overall survival [ Time Frame: 5 years ]
    defined as the time from surgery to death, whichever occurred first



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03170115


Contacts
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Contact: Alessandra Marins 00552132076666 amarins@inca.gov.br
Contact: Juliana Ominelli, MD 5521988734435 juominelli@hotmail.com

Locations
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Brazil
INCA- Instituto Nacional de Câncer Recruiting
Rio de Janeiro, Brazil, 20231-050
Contact: Alessandra Marins    00552132076666      
Contact: Andrea Roza       aroza@inca.gov.br   
Sub-Investigator: Juliana O Souza, MD         
Principal Investigator: Luiz Henrique Araujo, MD, PhD         
Sponsors and Collaborators
Instituto Nacional de Cancer, Brazil
Investigators
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Principal Investigator: Luiz Henrique Araujo, MD, PHD National Cancer Institute, France

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Responsible Party: Instituto Nacional de Cancer, Brazil
ClinicalTrials.gov Identifier: NCT03170115     History of Changes
Other Study ID Numbers: ICAR trial
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: February 28, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Instituto Nacional de Cancer, Brazil:
Rectal Cancer
Total neoadjuvant therapy
Induction chemotherapy
Aspirin colorectal cancer

Additional relevant MeSH terms:
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Aspirin
Adenocarcinoma
Rectal Neoplasms
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors