Rectal CancerPhase 2NCT05274945
Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
A Phase 2 study testing Radiotherapy, consolidation chemotherapy and TME or APR in people with Rectal Cancer, run by Alexandria University at 1 site in Egypt.
Trial summary
The National Comprehensive Cancer Network (NCCN) guidelines recommend trimodality treatment for patients with middle and low LARC with neoadjuvant chemoradiotherapy (NA-CRT), surgical resection with TME, plus additional chemotherapy (CT), in the adjuvant setting. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Radiotherapy, consolidation chemotherapy and TME or APR
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2020to 1 Jan 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of rectal cancer
- Inferior margin within 12 cm from the anal verge
- staging must be T3-4,N0 or any T, N +ve
Who cannot join
- Recurrent or metastatic disease.
- Rectal cancer on top of IBD.
- Hereditary non-polyposis colorectal cancer (HNPCC), or hereditary rectal cancer
Trial locations and contacts
1 site in 1 country.
About this study
The National Comprehensive Cancer Network (NCCN) guidelines recommend trimodality treatment for patients with middle and low LARC with neoadjuvant chemoradiotherapy (NA-CRT), surgical resection with TME, plus additional chemotherapy (CT), in the adjuvant setting. This has markedly reduced pelvic local recurrence from historically about 25% to about 5-10%. However, the 5-year distant relapse is approximately 30% and continues to be the major cause of rectal cancer death.
One strategy to address this issue is to deliver induction chemotherapy before surgery. Induction chemotherapy may be associated with better treatment compliance and may enable full systemic doses of chemotherapy to be delivered.
The above cited considerations, plus favorable data from preliminary reports exploring this strategy, provides a solid rationale for shifting systemic treatment earlier into the treatment paradigm. The current study will evaluate the efficacy and the safety of total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients as regards effects on tumor downstaging, pathological complete response, surgical difficulty and early functional outcome.
Read the detailed description
Colorectal cancer is the third most commonly diagnosed cancer and the third leading cause of cancer death in men and women in the USA.
Surgery using the total mesorectal excision (TME) remains the cornerstone of curative therapy for patients with nonmetastatic, locally advanced middle and low rectal cancer (LARC).
The National Comprehensive Cancer Network (NCCN) guidelines recommend trimodality treatment for patients with middle and low LARC with neoadjuvant chemoradiotherapy (NA-CRT), surgical resection with TME, plus additional chemotherapy (CT), in the adjuvant setting.
This has markedly reduced pelvic local recurrence from historically about 25% to about 5-10%. However, the 5-year distant relapse is approximately 30% and continues to be the major cause of rectal cancer death.
Several other trials have attempted to demonstrate the benefits of postoperative chemotherapy as an adjunct to preoperative radiation and surgery. These trials either failed to demonstrate an advantage, or were closed early due to poor accrual. One common theme among these trials is poor compliance with adjuvant chemotherapy. Completion rates for planned chemotherapy ranged from 43 to 74% in these trials.
The current rectal cancer treatment might lead to delay in the initiation of adjuvant chemotherapy especially in patients with postoperative complications, and this delay is theoretically disadvantageous in that it allows a window for growth of distant micrometastases which may already exist.
One strategy to address this issue is to deliver induction chemotherapy before surgery. Induction chemotherapy may be associated with better treatment compliance and may enable full systemic doses of chemotherapy to be delivered.
Other theoretical advantage of induction chemotherapy includes the possibility of shrinking or downstaging a locally advanced tumor, thereby facilitating more effective local treatment.
Initial chemotherapy also permits delivery of chemotherapy agents directly to the primary tumor while it has a fully intact vasculature, undisrupted by radiation or surgery.
It was supposed that increased chemoradiation-to-surgery interval would result in increased fibrosis and surgical difficulty.However, previous studies showed no increase in the technical difficulty of the operation with total neoadjuvant therapy.
The above cited considerations, plus favorable data from preliminary reports exploring this strategy, provides a solid rationale for shifting systemic treatment earlier into the treatment paradigm. The current study will evaluate the efficacy and the safety of total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients as regards effects on tumor downstaging, pathological complete response, surgical difficulty and early functional outcome.
- Conditions
- Rectal Cancer
- Being tested
- Radiotherapy, consolidation chemotherapy, TME or APR
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
Also called Radiation therapy
radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil
consolidation chemotherapyDrug
Also called CTX
6 cycles of FOLFOX or CAPOX
TME or APRProcedure or surgery
Also called proctectomy
total mesorectal excision or abdominoperineal resection
| Study group | Role | What they receive |
|---|---|---|
| total neoadjuvant therapy | Experimental | patients will be treated by total neoadjuvant therapy, including concurrent chemoradiotherapy in the form of radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil + Calcium leucoverin for first 4 days and last 3 days of radiotherapy or capecitabine at 825 mg\m2 twice daily. Then, after 2-3 weeks preoperative chemotherapy will be started in the form of 6 cycles of FOLFOX or CAPOX. Then, after 3-4 weeks surgery will be done. Receives: Radiation: Radiotherapy; Drug: consolidation chemotherapy; Procedure: TME or APR |
| standard neoadjuvant therapy | Active comparator | patients will be treated by standard neoadjuvant therapy , including concurrent chemoradiotherapy in the form of radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil + Calcium leucoverin for first 4 days and last 3 days of radiotherapy or capecitabine at 825 mg\m2 twice daily . Then, after 6-8 weeks surgery will be performed followed by adjuvant chemotherapy. Receives: Radiation: Radiotherapy; Procedure: TME or APR |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological assessment of response to treatment
The histological sections will be reviewed by the same pathologists and the regression grade will be quantified according to Mandard tumor regression grade with sore 1 representing complete response with no viable tumor cells to score 5 representing no regression.
Measured: 10 days
Secondary outcomes (1)
adverse events of chemotherapy
clinical and laboratory follow up to detect hematological and non hematological adverse effects of chemotherapy
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2022
- Study start1 Jan 2020
- Primary completion1 Jan 2022
- Study completion1 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexandria University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05274945
- Sponsor's protocol ID
- 122019
- Status last verified
- Jan 2022
- First submitted
- 7 Jan 2022
- Last updated
- 11 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT05274945
- Acronym / sponsor ID
- 122019
- Conditions
- Rectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Alexandria UniversityUniversity, hospital or other
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 1 Jan 2022 (actual)
- Study completion
- 1 Jan 2022 (actual)
- First posted
- 11 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The National Comprehensive Cancer Network (NCCN) guidelines recommend trimodality treatment for patients with middle and low LARC with neoadjuvant chemoradiotherapy (NA-CRT), surgical resection with TME, plus additional chemotherapy (CT), in the adjuvant setting. This has markedly reduced pelvic local recurrence from historically about 25% to about 5-10%. However, the 5-year distant relapse is approximately 30% and continues to be the major cause of rectal cancer death.
One strategy to address this issue is to deliver induction chemotherapy before surgery. Induction chemotherapy may be associated with better treatment compliance and may enable full systemic doses of chemotherapy to be delivered.
The above cited considerations, plus favorable data from preliminary reports exploring this strategy, provides a solid rationale for shifting systemic treatment earlier into the treatment paradigm. The current study will evaluate the efficacy and the safety of total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients as regards effects on tumor downstaging, pathological complete response, surgical difficulty and early functional outcome.
Detailed description
Colorectal cancer is the third most commonly diagnosed cancer and the third leading cause of cancer death in men and women in the USA.
Surgery using the total mesorectal excision (TME) remains the cornerstone of curative therapy for patients with nonmetastatic, locally advanced middle and low rectal cancer (LARC).
The National Comprehensive Cancer Network (NCCN) guidelines recommend trimodality treatment for patients with middle and low LARC with neoadjuvant chemoradiotherapy (NA-CRT), surgical resection with TME, plus additional chemotherapy (CT), in the adjuvant setting.
This has markedly reduced pelvic local recurrence from historically about 25% to about 5-10%. However, the 5-year distant relapse is approximately 30% and continues to be the major cause of rectal cancer death.
Several other trials have attempted to demonstrate the benefits of postoperative chemotherapy as an adjunct to preoperative radiation and surgery. These trials either failed to demonstrate an advantage, or were closed early due to poor accrual. One common theme among these trials is poor compliance with adjuvant chemotherapy. Completion rates for planned chemotherapy ranged from 43 to 74% in these trials.
The current rectal cancer treatment might lead to delay in the initiation of adjuvant chemotherapy especially in patients with postoperative complications, and this delay is theoretically disadvantageous in that it allows a window for growth of distant micrometastases which may already exist.
One strategy to address this issue is to deliver induction chemotherapy before surgery. Induction chemotherapy may be associated with better treatment compliance and may enable full systemic doses of chemotherapy to be delivered.
Other theoretical advantage of induction chemotherapy includes the possibility of shrinking or downstaging a locally advanced tumor, thereby facilitating more effective local treatment.
Initial chemotherapy also permits delivery of chemotherapy agents directly to the primary tumor while it has a fully intact vasculature, undisrupted by radiation or surgery.
It was supposed that increased chemoradiation-to-surgery interval would result in increased fibrosis and surgical difficulty.However, previous studies showed no increase in the technical difficulty of the operation with total neoadjuvant therapy.
The above cited considerations, plus favorable data from preliminary reports exploring this strategy, provides a solid rationale for shifting systemic treatment earlier into the treatment paradigm. The current study will evaluate the efficacy and the safety of total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients as regards effects on tumor downstaging, pathological complete response, surgical difficulty and early functional outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| total neoadjuvant therapy | Experimental | Radiation: Radiotherapy, Drug: consolidation chemotherapy, Procedure: TME or APRpatients will be treated by total neoadjuvant therapy, including concurrent chemoradiotherapy in the form of radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil + Calcium leucoverin for first 4 days and last 3 days of radiotherapy or capecitabine at 825 mg\m2 twice daily. Then, after 2-3 weeks preoperative chemotherapy will be started in the form of 6 cycles of FOLFOX or CAPOX. Then, after 3-4 weeks surgery will be done. |
| standard neoadjuvant therapy | Active comparator | Radiation: Radiotherapy, Procedure: TME or APRpatients will be treated by standard neoadjuvant therapy , including concurrent chemoradiotherapy in the form of radiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil + Calcium leucoverin for first 4 days and last 3 days of radiotherapy or capecitabine at 825 mg\m2 twice daily . Then, after 6-8 weeks surgery will be performed followed by adjuvant chemotherapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Clinical diagnosis of rectal cancer
- Inferior margin within 12 cm from the anal verge
- staging must be T3-4,N0 or any T, N +ve
Key exclusion criteria (3 listed)
- Recurrent or metastatic disease.
- Rectal cancer on top of IBD.
- Hereditary non-polyposis colorectal cancer (HNPCC), or hereditary rectal cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RadiotherapyAlso: Radiation therapyradiotherapy 45 Gy/ 25 fractions then boost 5.4 Gy/3 fractions with concurrent bolus 5-fluorouracil | Radiation | standard neoadjuvant therapy, total neoadjuvant therapy |
| consolidation chemotherapyAlso: CTX6 cycles of FOLFOX or CAPOX | Drug | total neoadjuvant therapy |
| TME or APRAlso: proctectomytotal mesorectal excision or abdominoperineal resection | Procedure or surgery | standard neoadjuvant therapy, total neoadjuvant therapy |
Primary outcome
pathological assessment of response to treatment
Time frame: 10 days
The histological sections will be reviewed by the same pathologists and the regression grade will be quantified according to Mandard tumor regression grade with sore 1 representing complete response with no viable tumor cells to score 5 representing no regression.
1 secondary outcome
adverse events of chemotherapy
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2022.
- Individual participant dataSharing planned: No
Related trials for Rectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiotherapy, consolidation chemotherapy and TME or APR in people with Rectal Cancer, run by Alexandria University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological assessment of response to treatment (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2022.