Recurrent Rectal CancerPhase 2TORCH-RNCT05628038
The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer
A Phase 2 study testing PD-1 antibody, Capecitabine and 5FU in people with Recurrent Rectal Cancer, run by Fudan University at 1 site in China.
Trial summary
The study is a prospective, single-center, single-arm, two-cohort, phase II clinical trial. Patients aged 18 years or older who had pelvic recurrence rectal cancer with or without resectable distant metastasis, with treatment naive disease (cohort A) or progressive disease after first-line chemotherapy (cohort B)… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Recurrent Rectal Cancer
- What is being tested?
- PD-1 antibody, Capecitabine and 5FU
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 1 siteChina
- Study dates
- 30 Nov 2022to 1 Dec 2025
- 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
- Patient is 18-75 years old at the time of signing the informed consent form.
- ECOG performance status 0-1.
- MRI/enhanced CT confirmed pelvic recurrence. According to RECIST 1.1, there is at least one measurable pelvic lesion.
- Distant metastasis lesions are no more than 5 and metastatic organ are no more than 3.
- No prior radiotherapy within 6 month.
- Previous system therapy. Patients Group Cohort A: participants with pelvic recurrence who have not previously been treated with first-line chemotherapy. Cohort B: Patients with disease progression or new lesions after first-line chemotherapy.
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- Has an investigator determined life expectancy of at least 24 weeks.
- Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
- Non pregnant or lactating patients. Effective contraceptive methods should be used during the study and within 6 months of the last administration.
- Fully informed and willing to provide written informed consent for the trial.
Who cannot join
- Neutrophil < 1.5×10^9/L, PLT < 100×10^9/L (PLT < 80×10^9/L in patients with liver metastasis), or Hb < 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria.
- TBIL > 1.5 ULN, or TBIL > 2.5 ULN in patients with liver metastasis.
- AST or ALT > 2.5 ULN, or ALT and / or AST > 5 ULN in patients with liver metastasis.
- Cr > 1.5 ULN, or creatinine clearance < 50ml / min (calculated according to Cockcroft Gault formula).
- APTT > 1.5 ULN, PT > 1.5 ULN (subject to the normal value of the clinical trial research center).
- Serious electrolyte abnormalities.
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- Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h.
- Uncontrolled hypertension: SBP >140mmHg or DBP > 90mmHg.
- The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumours with active bleeding; or other conditions likely to cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation or gastrointestinal fistula after surgical treatment.
- A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months.
- A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF<50%).
- Uncontrolled malignant pleural effusion, ascites, or pericardial effusion.
- History of anti-PD-1, PD-L1, PD-L2, CTLA-4 or any other specific T cell co-stimulation or checkpoint pathway targeted therapy.
- The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1).
- A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10^4/ml), HCV infection or HCV DNA positive(≥1×10^3/ml) and liver cirrhosis.
- Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication; Or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period.
- The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.
- Serious mental abnormalities.
- The diameter of brain metastasis is greater than 3cm or the total volume is greater than 30cc.
- Clinical or radiological evidence of spinal cord compression, or tumours within 3 mm of the spinal cord on MRI.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Zhen Zhang, MD,PhD, 18801735029, zhen_zhang@fudan.edu.cn
About this study
Official title: Hypofractionated Radiotherapy Combined With Toripalimab and Chemotherapy +/- Target Therapy for Locally Recurrent Rectal Cancer: a Single-arm, Two-cohort, Phase II Trial (TORCH-R)
The study is a prospective, single-center, single-arm, two-cohort, phase II clinical trial. Patients aged 18 years or older who had pelvic recurrence rectal cancer with or without resectable distant metastasis, with treatment naive disease (cohort A) or progressive disease after first-line chemotherapy (cohort B), Eastern Cooperative Oncology Group performance status of 0-1, will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history), 18 weeks toripalimab and investigator's choice of chemotherapy +/- target therapy, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles, followed by multidisciplinary team (MDT) for decision:follow-up of complete response (CR), radical surgery, sustained treatment of non resection, or exit.
The primary endpoint was local objective response rate. Secondary endpoints were extrapelvic objective response rate, R0 resection rate, duration of response, progression-free survival, overall survival, and safety and tolerability of the treatment.
Shanghai Junshi Biomedical Technology Co., Ltd. Provides the first three cycles of toripalimab for free and has purchased liability insurance for clinical trial subjects.
Read the detailed description
For patients with locally recurrent rectal cancer (LRRC), response rate of chemoradiotherapy is 40-50% and only approximately 40-50% of patients with recurrent rectal cancer can undergo R0 resection. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Thus, for LRRC patients, addition of immunotherapy to CRT is likely to further improve the response rate and prognosis.
- Conditions
- Recurrent Rectal Cancer
- Being tested
- PD-1 antibody, Capecitabine, 5FU, folinic acid, Oxaliplatin
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 antibodyDrug
Also called Toripalimab
PD-1 antibody (Toripalimab): 240mg q3w or 160mg q2w
CapecitabineDrug
Also called Xeloda
Capecitabine: 1000mg/m2 d1-14 q3w
5FUDrug
400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr)
folinic acidDrug
400 mg/m2 q2w
OxaliplatinDrug
130 mg/m² q3w or 85 mg/m² q2w
IrinotecanDrug
180 mg/m² q2w and 200 mg/m² q3w
RaltitrexedDrug
2 mg/m² q2w and 3 mg/m² q3w
CetuximabDrug
400 mg/m² q2w
BevacizumabDrug
5 mg/kg q2w or 7.5mg/kg q3w
RadiationRadiation
25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence tumor.
35-60Gy/5-8Fx irradiation for distance metastasis tumor.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | The enrolled patients will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence.
Cohort A patients will receive CAPOX, FOLFIRI or mFOLFOX6 chemotherapy andcohort B patients will receive CAPOX, FOLFIRI, mFOLFOX6, mXELIRI, irinotecan and raltitrexed, or oxaliplatin and raltitrexed chemotherapy, based on previous chemotherapy and adverse reactions to chemotherapy agents or at the discretion of the oncologist.
All metastasis sites will receive stereotactic ablative radiotherapy (SABR) between chemoimmunotherapy cycles. Five-fraction regimens (25-50Gy/5Fx) are delivered daily. Dose Constraints are based on SABR-COMET 10 trial.
Besides, according to the medical oncologist recommendation, patients with unresectable pelvic recurrence or distant metastasis will receive target therapy based on the KRAS/NRAS/BRAF mutation station. Receives: Drug: PD-1 antibody; Drug: Capecitabine; Drug: 5FU; Drug: folinic acid; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Raltitrexed; Drug: Cetuximab; Drug: Bevacizumab; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local objective response rate
the proportion of patients with the best pelvic response of confirmed complete or partial response according to RECIST 1.1, as assessed by the investigator.
Measured: up to 1 year
Secondary outcomes (6)
Extrapelvic objective response rate
proportion of patients with confirmed extrapelvic complete or partial response per RECIST 1.1.
Measured: up to 1 year
R0 resection rate
the proportion of patients who achieve R0 resection of pelvic recurrent tumour after therapy.
Measured: up to 1 year
Duration of response (DOR)
time from the first documented pelvic objective response to pelvic or extrapelvic disease progression in patients with confirmed response.
Measured: up to 1 year
Progression-Free Survival
time from the date of start treatment until disease progression or censored at last follow-up or death.
Measured: up to 3 year
Overall Survival
from the date of start treatment until the date of death from any cause or censored at last follow-up.
Measured: up to 3 year
Safety and tolerability of the treatment
proportion of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2022
- Study start30 Nov 2022
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Rectal CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 93 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhen Zhang, Fudan University
- Investigators
- Zhen Zhang, MD PhD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05628038
- Sponsor's protocol ID
- FDRT-2022-289-3006
- Acronym
- TORCH-R
- Status last verified
- Sep 2024
- First submitted
- 17 Nov 2022
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wan J, Wu R, Fu M, Shen L, Zhang H, Wang Y, Wang Y, Zhou S, Chen Y, Xia F, Zhang Z. TORCH-R trial protocol: hypofractionated radiotherapy combined with chemotherapy and toripalimab for locally recurrent rectal cancer: a prospective, single-arm, two-cohort, phase II trial. Front Oncol. 2023 Nov 20;13:1304767. doi: 10.3389/fonc.2023.1304767. eCollection 2023.
PubMed 38053659
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypofractionated Radiotherapy Combined With Toripalimab and Chemotherapy +/- Target Therapy for Locally Recurrent Rectal Cancer: a Single-arm, Two-cohort, Phase II Trial (TORCH-R)
- ClinicalTrials.gov ID
- NCT05628038
- Acronym / sponsor ID
- TORCH-R / FDRT-2022-289-3006
- Conditions
- Recurrent Rectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 93 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 30 Nov 2022 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 28 Nov 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 study is a prospective, single-center, single-arm, two-cohort, phase II clinical trial. Patients aged 18 years or older who had pelvic recurrence rectal cancer with or without resectable distant metastasis, with treatment naive disease (cohort A) or progressive disease after first-line chemotherapy (cohort B), Eastern Cooperative Oncology Group performance status of 0-1, will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history), 18 weeks toripalimab and investigator's choice of chemotherapy +/- target therapy, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles, followed by multidisciplinary team (MDT) for decision:follow-up of complete response (CR), radical surgery, sustained treatment of non resection, or exit.
The primary endpoint was local objective response rate. Secondary endpoints were extrapelvic objective response rate, R0 resection rate, duration of response, progression-free survival, overall survival, and safety and tolerability of the treatment.
Shanghai Junshi Biomedical Technology Co., Ltd. Provides the first three cycles of toripalimab for free and has purchased liability insurance for clinical trial subjects.
Detailed description
For patients with locally recurrent rectal cancer (LRRC), response rate of chemoradiotherapy is 40-50% and only approximately 40-50% of patients with recurrent rectal cancer can undergo R0 resection. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Thus, for LRRC patients, addition of immunotherapy to CRT is likely to further improve the response rate and prognosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: PD-1 antibody, Drug: Capecitabine, Drug: 5FU, Drug: folinic acid, Drug: Oxaliplatin, Drug: Irinotecan, Drug: Raltitrexed, Drug: Cetuximab, Drug: Bevacizumab, Radiation: RadiationThe enrolled patients will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence. Cohort A patients will receive CAPOX, FOLFIRI or mFOLFOX6 chemotherapy andcohort B patients will receive CAPOX, FOLFIRI, mFOLFOX6, mXELIRI, irinotecan and raltitrexed, or oxaliplatin and raltitrexed chemotherapy, based on previous chemotherapy and adverse reactions to chemotherapy agents or at the discretion of the oncologist. All metastasis sites will receive stereotactic ablative radiotherapy (SABR) between chemoimmunotherapy cycles. Five-fraction regimens (25-50Gy/5Fx) are delivered daily. Dose Constraints are based on SABR-COMET 10 trial. Besides, according to the medical oncologist recommendation, patients with unresectable pelvic recurrence or distant metastasis will receive target therapy based on the KRAS/NRAS/BRAF mutation station. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patient is 18-75 years old at the time of signing the informed consent form.
- ECOG performance status 0-1.
- MRI/enhanced CT confirmed pelvic recurrence. According to RECIST 1.1, there is at least one measurable pelvic lesion.
- Distant metastasis lesions are no more than 5 and metastatic organ are no more than 3.
- No prior radiotherapy within 6 month.
Key exclusion criteria (20 listed)
- Neutrophil < 1.5×10^9/L, PLT < 100×10^9/L (PLT < 80×10^9/L in patients with liver metastasis), or Hb < 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria.
- TBIL > 1.5 ULN, or TBIL > 2.5 ULN in patients with liver metastasis.
- AST or ALT > 2.5 ULN, or ALT and / or AST > 5 ULN in patients with liver metastasis.
- Cr > 1.5 ULN, or creatinine clearance < 50ml / min (calculated according to Cockcroft Gault formula).
- APTT > 1.5 ULN, PT > 1.5 ULN (subject to the normal value of the clinical trial research center).
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 |
|---|---|---|
| PD-1 antibodyAlso: ToripalimabPD-1 antibody (Toripalimab): 240mg q3w or 160mg q2w | Drug | Treatment arm |
| CapecitabineAlso: XelodaCapecitabine: 1000mg/m2 d1-14 q3w | Drug | Treatment arm |
| 5FU400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr) | Drug | Treatment arm |
| folinic acid400 mg/m2 q2w | Drug | Treatment arm |
| Oxaliplatin130 mg/m² q3w or 85 mg/m² q2w | Drug | Treatment arm |
| Irinotecan180 mg/m² q2w and 200 mg/m² q3w | Drug | Treatment arm |
| Raltitrexed2 mg/m² q2w and 3 mg/m² q3w | Drug | Treatment arm |
| Cetuximab400 mg/m² q2w | Drug | Treatment arm |
| Bevacizumab5 mg/kg q2w or 7.5mg/kg q3w | Drug | Treatment arm |
| Radiation25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence tumor. 35-60Gy/5-8Fx irradiation for distance metastasis tumor. | Radiation | Treatment arm |
Primary outcome
Local objective response rate
Time frame: up to 1 year
the proportion of patients with the best pelvic response of confirmed complete or partial response according to RECIST 1.1, as assessed by the investigator.
6 secondary outcomes
Extrapelvic objective response rate
Time frame: up to 1 year
R0 resection rate
Time frame: up to 1 year
Duration of response (DOR)
Time frame: up to 1 year
Progression-Free Survival
Time frame: up to 3 year
Overall Survival
Time frame: up to 3 year
Safety and tolerability of the treatment
Time frame: up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Derived from this study: PubMed 38053659Wan J, Wu R, Fu M, Shen L, Zhang H, Wang Y, Wang Y, Zhou S, Chen Y, Xia F, Zhang Z. TORCH-R trial protocol: hypofractionated radiotherapy combined with chemotherapy and toripalimab for locally recurrent rectal cancer: a prospective, single-arm, two-cohort, phase II trial. Front Oncol. 2023 Nov 20;13:1304767. doi: 10.3389/fonc.2023.1304767. eCollection 2023.
- Individual participant dataSharing planned: Undecided
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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.
Zhen Zhang, MD PhD principal investigator
Fudan University
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 PD-1 antibody, Capecitabine and 5FU in people with Recurrent Rectal Cancer, run by Fudan University at 1 site in China.
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 10 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 1 Oct 2024. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhen Zhang, MD PhD (18801735029, zhen_zhang@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local objective response rate (time frame: up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05628038, which also lists 1 linked publication.
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 1 Oct 2024.