Rectal Neoplasm Malignant CarcinomaNCT04227886
Study on Predictive Biomarkers of Neoadjuvant Chemoradiotherapy for Rectal Cancer
An observational study of Rectal Neoplasm Malignant Carcinoma and Chemoradiotherapy, run by Fudan University at 1 site in China.
Trial summary
Backgrounds: A multicenter randomized phase III trial (NCT02605265) proved that adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Neoplasm Malignant Carcinoma, Chemoradiotherapy, Neoadjuvant Therapy
- What is being tested?
- Radiation and Capecitabine-Irinotecan Combination
- Type of treatment
- Surgery or procedure
- How many people
- 250 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2019to 31 Dec 2021
- Phase
- Observational
- 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
Study population: Stage T3 or T4 and/or N+ rectal adenocarcinoma cancer eligible for neoadjuvant chemoradiation
Who may be able to join
- Pathological confirmed adenocarcinoma
- Clinical stage T3-4 andor N+
- The distance from anal verge less than 12 cm
- No suspicious metastatic disease (M1)
- ECOG PS 0-1
- UGT1A1*28 6/6 or 6/7
- No previous anti-cancer therapy
Who cannot join
- Pregnancy or breast-feeding women
- Serious medical illness
- Baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
- DPD deficiency
- UGT1A1*28 7/7
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Ji Zhu, MD, +86-2164175590 ext. 81607, leo.zhu@126.com
About this study
Official title: A Prospective, Observational, Multicenter Study on Biomarkers for Predicting the Efficacy and Toxicities of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer Based on Tissue and Plasma Exosome RNA
Backgrounds: A multicenter randomized phase III trial (NCT02605265) proved that adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable.
Purposes: This study aims to identify the predictive biomarkers (from patients' tumor biopsy samples and peripheral blood samples before neoadjuvant therapy) for predicting the response and toxicities to neoadjuvant therapy to stratify patients and optimize treatment strategy.
Read the detailed description
OBJECTIVES:
Primary:
- Establish a predictive model for response based on tissue RNA and plasma exosome RNA
- Establish a predictive model for toxicities based on tissue RNA and plasma exosome RNA
Secondary:
- Internal validation of the established predictive models
- External validation of the established predictive models
OUTLINE:
-Treatment: Patients receive neoadjuvant therapy and surgery per the protocol. Samples collection Tumor tissue and peripheral blood will be collected prior to neoadjuvant therapy.
-Grouping: Response: Patients will be dichotomized into two groups based on the TRG. TRG of 0-1 is defined as good response. TRG of 2-3 is defined as poor response.
Toxicities: Patients will be dichotomized into two groups based on the grade of AEs. No grade 3-4 toxicities occurs during neoadjuvant therapy is defined as light toxicities. Grade 3-4 toxicities occur during neoadjuvant therapy is defined as heavy toxicities.
-Predictive Model Construction: Using RNA sequencing method to obtain the whole genome transcription profiles of the tumor tissue and plasm exosome RNA. Compare the gene expression differences between the two response groups and the two toxicity groups. Predictive models of response and toxicities are constructed.
-Internal Validation: Patients treated at Fudan University Shanghai Cancer Center (N=50) per the protocol will be enrolled as the internal validation cohort. Samples of tissue and plasm will be collected and analyzed. The performance of the model will be evaluated by the correlation of the predicted response/toxicities and the actual response/toxicities.
-External Validation: Patients treated at Liao'ning Cancer Hospital \& Institute (N=50) and Harbin Medical University Cancer Hospital (N=50) per the protocol will be enrolled as two external validation cohorts. Samples of tissue and plasm will be collected and analyzed. The performance of the model will be evaluated by the correlation of the predicted response/toxicities and the actual response/toxicities.
- Conditions
- Rectal Neoplasm Malignant Carcinoma, Chemoradiotherapy, Neoadjuvant Therapy, Predictive Biomarkers, Adenocarcinoma
- Being tested
- Radiation, Capecitabine-Irinotecan Combination
- Keywords
- Neoadjuvant Chemoradiation, Prediction Model, Treatment Response, Toxicities, Irinotecan, Tissue RNA, Plasma exosome
- Medical subject headings
- Rectal Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiationRadiation
Neoadjuvant radiotherapy consisted of 50 Gy in 25 fractions using intensity-modulated radiotherapy to the primary tumor and to mesorectal, presacral, and internal iliac lymph nodes.
Capecitabine-Irinotecan CombinationDrug
The concurrent chemotherapy consists of capecitabine 625 mg/m2 twice daily 5 days per week and combined with weekly irinotecan. The irinotecan dose was used based on UGT1A1 genotype of 80mg/m2 for UGT1A1*1*1 or 65mg/m2 for UGT1A1*1*28 weekly, followed by a cycle of XELIRI.
| Study group | Role | What they receive |
|---|---|---|
| Good response | TRG of 0-1 is defined as good response. Receives: Radiation: Radiation; Drug: Capecitabine-Irinotecan Combination | |
| Poor response | TRG of 2-3 is defined as poor response. Receives: Radiation: Radiation; Drug: Capecitabine-Irinotecan Combination | |
| Light toxicity | No grade 3-4 toxicities occur during neoadjuvant therapy. Receives: Radiation: Radiation; Drug: Capecitabine-Irinotecan Combination | |
| Heavy toxicity | Grade 3-4 toxicities occur during neoadjuvant therapy. Receives: Radiation: Radiation; Drug: Capecitabine-Irinotecan Combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
TRG
Tumor regression grade
Measured: Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy
Toxicities
Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0
Measured: Up to 2 years
Secondary outcomes (4)
Overall Survival
The total survival time of the participants from joining the group to the death
Measured: 3 years
Progression-free Survival
The time period that from participants joining the groups to the progression of disease (recurrence or metastasis) or death of any cause.
Measured: 3 years
Local Control rate
The time period that from participants joining the groups to the date of first documented pelvic failure.
Measured: 3 years
pCR
Pathologic Complete Response
Measured: Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start1 Dec 2019
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal Neoplasm Malignant CarcinomaStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Liaoning Cancer Hospital & Institute, Harbin Medical University
- Responsible party
- Principal investigator, Zhu Ji, Fudan University
- Investigators
- Ji Zhu, MD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04227886
- Sponsor's protocol ID
- FDRT-011
- Status last verified
- Jan 2020
- First submitted
- 30 Dec 2019
- Last updated
- 14 Jan 2020
- Results posted
- No
- Data monitoring committee
- 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 14 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Observational, Multicenter Study on Biomarkers for Predicting the Efficacy and Toxicities of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer Based on Tissue and Plasma Exosome RNA
- ClinicalTrials.gov ID
- NCT04227886
- Acronym / sponsor ID
- FDRT-011
- Conditions
- Rectal Neoplasm Malignant Carcinoma, Chemoradiotherapy, Neoadjuvant Therapy, Predictive Biomarkers, Adenocarcinoma
- Keywords
- Neoadjuvant Chemoradiation, Prediction Model, Treatment Response, Toxicities, Irinotecan, Tissue RNA, Plasma exosome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Collaborators
- Liaoning Cancer Hospital & Institute, Harbin Medical University
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 14 Jan 2020 (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.
Backgrounds: A multicenter randomized phase III trial (NCT02605265) proved that adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable.
Purposes: This study aims to identify the predictive biomarkers (from patients' tumor biopsy samples and peripheral blood samples before neoadjuvant therapy) for predicting the response and toxicities to neoadjuvant therapy to stratify patients and optimize treatment strategy.
Detailed description
OBJECTIVES:
Primary:
- Establish a predictive model for response based on tissue RNA and plasma exosome RNA
- Establish a predictive model for toxicities based on tissue RNA and plasma exosome RNA
Secondary:
- Internal validation of the established predictive models
- External validation of the established predictive models
OUTLINE:
-Treatment: Patients receive neoadjuvant therapy and surgery per the protocol. Samples collection Tumor tissue and peripheral blood will be collected prior to neoadjuvant therapy.
-Grouping: Response: Patients will be dichotomized into two groups based on the TRG. TRG of 0-1 is defined as good response. TRG of 2-3 is defined as poor response.
Toxicities: Patients will be dichotomized into two groups based on the grade of AEs. No grade 3-4 toxicities occurs during neoadjuvant therapy is defined as light toxicities. Grade 3-4 toxicities occur during neoadjuvant therapy is defined as heavy toxicities.
-Predictive Model Construction: Using RNA sequencing method to obtain the whole genome transcription profiles of the tumor tissue and plasm exosome RNA. Compare the gene expression differences between the two response groups and the two toxicity groups. Predictive models of response and toxicities are constructed.
-Internal Validation: Patients treated at Fudan University Shanghai Cancer Center (N=50) per the protocol will be enrolled as the internal validation cohort. Samples of tissue and plasm will be collected and analyzed. The performance of the model will be evaluated by the correlation of the predicted response/toxicities and the actual response/toxicities.
-External Validation: Patients treated at Liao'ning Cancer Hospital \& Institute (N=50) and Harbin Medical University Cancer Hospital (N=50) per the protocol will be enrolled as two external validation cohorts. Samples of tissue and plasm will be collected and analyzed. The performance of the model will be evaluated by the correlation of the predicted response/toxicities and the actual response/toxicities.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Good response | – | Radiation: Radiation, Drug: Capecitabine-Irinotecan CombinationTRG of 0-1 is defined as good response. |
| Poor response | – | Radiation: Radiation, Drug: Capecitabine-Irinotecan CombinationTRG of 2-3 is defined as poor response. |
| Light toxicity | – | Radiation: Radiation, Drug: Capecitabine-Irinotecan CombinationNo grade 3-4 toxicities occur during neoadjuvant therapy. |
| Heavy toxicity | – | Radiation: Radiation, Drug: Capecitabine-Irinotecan CombinationGrade 3-4 toxicities occur during neoadjuvant therapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Stage T3 or T4 and/or N+ rectal adenocarcinoma cancer eligible for neoadjuvant chemoradiation
Key inclusion criteria (7 listed)
- Pathological confirmed adenocarcinoma
- Clinical stage T3-4 andor N+
- The distance from anal verge less than 12 cm
- No suspicious metastatic disease (M1)
- ECOG PS 0-1
Key exclusion criteria (5 listed)
- Pregnancy or breast-feeding women
- Serious medical illness
- Baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
- DPD deficiency
- UGT1A1*28 7/7
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 |
|---|---|---|
| RadiationNeoadjuvant radiotherapy consisted of 50 Gy in 25 fractions using intensity-modulated radiotherapy to the primary tumor and to mesorectal, presacral, and internal iliac lymph nodes. | Radiation | Good response, Heavy toxicity, Light toxicity, Poor response |
| Capecitabine-Irinotecan CombinationThe concurrent chemotherapy consists of capecitabine 625 mg/m2 twice daily 5 days per week and combined with weekly irinotecan. The irinotecan dose was used based on UGT1A1 genotype of 80mg/m2 for UGT1A1*1*1 or 65mg/m2 for UGT1A1*1*28 weekly, followed by a cycle of XELIRI. | Drug | Good response, Heavy toxicity, Light toxicity, Poor response |
Primary outcome
TRG
Time frame: Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy
Tumor regression grade
Toxicities
Time frame: Up to 2 years
Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0
4 secondary outcomes
Overall Survival
Time frame: 3 years
Progression-free Survival
Time frame: 3 years
Local Control rate
Time frame: 3 years
pCR
Time frame: Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2020.
- Individual participant dataSharing planned: No
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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.
Ji Zhu, MD 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?
An observational study of Rectal Neoplasm Malignant Carcinoma and Chemoradiotherapy, 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 7 inclusion and 5 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 14 Jan 2020. 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.
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 Ji Zhu, MD (+86-2164175590 ext. 81607, leo.zhu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TRG (time frame: Surgery scheduled 6-8 weeks after the end of neoadjuvant therapy). The study lists 2 primary outcomes in all. 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 14 Jan 2020.