Phase II/III Study to Assess the Efficacy of Neoadjuvant Consolidation Chemotherapy in Rectal Cancer Patients.

NCT03957733 | Unknown Phase 2

• 1 other identifier: 17-329
• Study Type: interventional
• Target: 338
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II/III randomized study involving non-metastatic rectal cancer patients who are candidates for neoadjuvant chemoradiotherapy. Eligible patients will be randomized between two treatment arms: Experimental arm: Long course CRT is followed by 4 cycles of combination chemotherapy of modified FOLFOX6 or 3 cycles of XELOX and then surgery. After surgery, patients with pT0-2 N0 will not receive adjuvant chemotherapy. Patients with higher pathological stage will receive adjuvant chemotherapy (4 cycles of modified FOLFOX6 or 3 cycles of XELOX). Standard arm: Long course CRT will be followed by surgery 10-12 weeks after the end of CRT. After surgery, patients with pT0-2 N0 will not receive adjuvant chemotherapy. Patients with higher pathological stage will receive adjuvant chemotherapy (8 cycles of modified FOLFOX6 or 6 cycles of XELOX). The study aims to assess the efficacy of consolidation chemotherapy given in the interval between the end of CRT and surgery to allow for early initiation of systemic therapy aiming to decrease distant relapse rate and enhancing pathological response.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Pathologic complete response rate (pCR).

  pCR will be defined as the absence of viable tumor cells in the primary tumor and in the lymph nodes (ypT0N0) by histopathological assessment of the surgical specimen at the time of definitive rectal surgery.

  3 years

• 3-year disease free survival (DFS) rate.

  3-year DFS will be defined as the percentage of patients alive without recurrence of disease at 3 years measured from the date of randomization

  3 years

Secondary Outcomes (4)

• Overall survival (OS)

  5 years

• Radiological response by MRI imaging before surgery.

  3 years

• Short and long-term toxicity.

  3 - 5 years

• Surgical complications.

  3 years

Study Arms (2)

Experimental arm

EXPERIMENTAL

Long course CRT is followed by 4 cycles of combination chemotherapy of modified FOLFOX6 or 3 cycles of XELOX (capecitabine and oxaliplatin) and surgery. Consolidation chemotherapy will start 2-4 weeks after the end of CRT. Surgery will be performed 2-4 weeks after the last chemotherapy cycle. After surgery, patients with pT0-2 N0 will not receive adjuvant chemotherapy. Patients with higher pathological stage will receive adjuvant chemotherapy (4 cycles of modified FOLFOX6 or 3 cycles of XELOX).

Drug: Chemotherapy

Standard arm

NO INTERVENTION

Long course CRT will be followed by surgery 10-12 weeks after the end of CRT. After surgery, patients with pT0-2 N0 will not receive adjuvant chemotherapy. Patients with higher pathological stage will receive adjuvant chemotherapy (8 cycles of modified FOLFOX6 or 6 cycles of XELOX).

Interventions

Chemotherapy DRUG

Long course CRT is followed by 4 cycles of combination chemotherapy of modified FOLFOX6 or 3 cycles of XELOX (capecitabine and oxaliplatin) and then surgery

Also known as: Folfox, Xelox

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at diagnosis
• Histopathological diagnosis of rectal adenocarcinoma
• ECOG Performance Status (PS): 0- 2
• Clinical Stage: T2 N1-2, T3N0-2, T4 N0-2 based on pelvic MRI. Lymph node will be considered radiologically positive if: - size (short axis≥ 1cm) and/or - Morphological changes: irregular outlines/ abnormal signal intensity, positive enhancement.
• The standard treatment recommendation of included patients in the absence of a clinical trial would be combined modality neoadjuvant CRT followed by curative intent surgical resection.
• Primary surgeon is planning to perform Total Mesorectal Excision (TME).
• The following laboratory values must be obtained ≤ 28 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin \> 8.0 g/dl (transfusion permitted)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• SGOT (AST) ≤ 3 x ULN
• SGPT (ALT) ≤ 3 x ULN
• Creatinine ≤1.5 x ULN or Creatinine clearance \> 50ml/minute by Cockcroft-Gault formula.
• Negative pregnancy test ≤ 7 days prior to registration for women of childbearing potential only.

You may not qualify if:

• Extensive growth into the sacrum or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is seen.
• Presence of metastatic disease or recurrent rectal tumor.
• Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative Colitis.
• Concomitant malignancies, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Any contraindications to MRI (e.g. patients with pacemakers)
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the past 12 months.
• Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract.
• Co-morbid illnesses or other concurrent disease which, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Any investigational treatment for rectal cancer within the past year.
• Pregnancy or breast feeding.

Sponsors & Collaborators

• King Abdullah Medical City: lead
• King Faisal Specialist Hospital & Research Center: collaborator
• King Saud Medical City: collaborator
• Al Hada Military Hospital: collaborator

Study Sites (1)

King Abdullah Medical City, Holy Capital

Mecca, Makkah Western, 21955, Saudi Arabia

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Drug Therapy; Folfox protocol; XELOX

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Shereef E Mohammad

  King Abdullah Medical City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rania M Felemban, MSc

CONTACT

+96625549999; felembanr@kamc.med.sa

Wedian O Almowlad, MSc

CONTACT

+96625549999; Almwlld.W@kamc.med.sa

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Phase II/III randomized controlled parallel group study. Patients are randomized between Chemoradiotherapy followed by surgery or chemoradiotherapy followed by folfox/xelox chemotherapy then surgery

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 21, 2019
• Study Start: November 23, 2017
• Primary Completion: May 30, 2022
• Study Completion: November 23, 2025
• Last Updated: April 6, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1)