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

Sponsor
King Abdullah Medical City (Other)
Overall Status
Recruiting
CT.gov ID
NCT03957733
Collaborator
King Faisal Specialist Hospital & Research Center (Other), King Saud Medical City (Other), Al Hada Military Hospital (Other)
338
1
2
96
3.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
338 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Phase II/III randomized controlled parallel group study. Patients are randomized between Chemoradiotherapy followed by surgery or chemoradiotherapy followed by folfox/xelox chemotherapy then surgeryPhase II/III randomized controlled parallel group study. Patients are randomized between Chemoradiotherapy followed by surgery or chemoradiotherapy followed by folfox/xelox chemotherapy then surgery
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II/III Randomized Multicentre Study Comparing Neoadjuvant Chemoradiotherapy Followed by Consolidation Chemotherapy to Neoadjuvant Chemoradiotherapy Alone in Non-metastatic Rectal Cancer Patients.
Actual Study Start Date :
Nov 23, 2017
Anticipated Primary Completion Date :
May 30, 2022
Anticipated Study Completion Date :
Nov 23, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Experimental arm

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
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
Other Names:
  • Folfox
  • Xelox
  • No Intervention: 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).

    Outcome Measures

    Primary Outcome Measures

    1. Pathologic complete response rate (pCR). [3 years]

      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.

    2. 3-year disease free survival (DFS) rate. [3 years]

      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

    Secondary Outcome Measures

    1. Overall survival (OS) [5 years]

      defined as the time from randomization to death from any cause

    2. Radiological response by MRI imaging before surgery. [3 years]

    3. Short and long-term toxicity. [3 - 5 years]

      According to common toxicology criteria of adverse events, version 3

    4. Surgical complications. [3 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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.

    • Patient of child-bearing potential is willing to employ an adequate contraception method

    • Provide informed written consent

    • Willing to return to the enrolling medical site for all study assessments

    Exclusion Criteria:
    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 King Abdullah Medical City, Holy Capital Mecca Makkah Western Saudi Arabia 21955

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Shereef E Mohammad, King Abdullah Medical City

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    King Abdullah Medical City
    ClinicalTrials.gov Identifier:
    NCT03957733
    Other Study ID Numbers:
    • 17-329
    First Posted:
    May 21, 2019
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 6, 2022