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

Primary Purpose

Rectal Cancer

Status

Recruiting

Phase

Phase 2

Locations

Saudi Arabia

Study Type

Interventional

Intervention

Chemotherapy

About this trial

This is an interventional treatment trial for Rectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

King Abdullah Medical City, Holy CapitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Experimental arm

Standard arm

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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-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

Secondary Outcome Measures

Overall survival (OS)

defined as the time from randomization to death from any cause

Radiological response by MRI imaging before surgery.

Short and long-term toxicity.

According to common toxicology criteria of adverse events, version 3

Surgical complications.

Full Information

NCT ID

NCT03957733

First Posted

May 1, 2019

Last Updated

April 5, 2022

Sponsor

King Abdullah Medical City

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03957733

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 23, 2017 (Actual)

Primary Completion Date

May 30, 2022 (Anticipated)

Study Completion Date

November 23, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

King Abdullah Medical City

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

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 surgery

Masking

None (Open Label)

Allocation

Randomized

Enrollment

338 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental arm

Arm Type

Experimental

Arm Description

Arm Title

Standard arm

Arm Type

No Intervention

Arm Description

Intervention Type

Drug

Intervention Name(s)

Chemotherapy

Other Intervention Name(s)

Folfox, Xelox

Intervention Description

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

Primary Outcome Measure Information:

Title

Pathologic complete response rate (pCR).

Description

Time Frame

3 years

Title

3-year disease free survival (DFS) rate.

Description

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

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

defined as the time from randomization to death from any cause

Time Frame

5 years

Title

Radiological response by MRI imaging before surgery.

Time Frame

3 years

Title

Short and long-term toxicity.

Description

According to common toxicology criteria of adverse events, version 3

Time Frame

3 - 5 years

Title

Surgical complications.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rania M Felemban, MSc

Phone

+96625549999

Ext

18013

felembanr@kamc.med.sa

First Name & Middle Initial & Last Name or Official Title & Degree

Wedian O Almowlad, MSc

Phone

+96625549999

Ext

18004

Almwlld.W@kamc.med.sa

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shereef E Mohammad

Organizational Affiliation

King Abdullah Medical City

Official's Role

Principal Investigator

Facility Information:

Facility Name

King Abdullah Medical City, Holy Capital

City

Mecca

State/Province

Makkah Western

ZIP/Postal Code

21955

Country

Saudi Arabia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rania M Felemban, Msc

Phone

0096625549999

Ext

18013

felembanr@kamc.med.sa

First Name & Middle Initial & Last Name & Degree

Wedian O Almowlad, Msc

Phone

0096625549999

Ext

18004

Almwlld.W@kamc.med.sa

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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