ChemotherapyPhase 2NCT04891016
Toripalimab Plus FLOT in Locally Advanced Gastric Cancer
A Phase 2 study testing FLOT combined with toripalimab in people with Chemotherapy and Immune Checkpoint Inhibitor, run by Henan Cancer Hospital at 1 site in China.
Trial summary
Neoadjuvant chemoimmunotherapy for locally advanced gastric and gastroesophageal junction (G/GEJ) cancer is currently under investigation. Most clinical studies have simply combined chemotherapy with anti-PD-1 therapy without considering the impact of chemotherapy drugs on activated immune cells. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chemotherapy, Immune Checkpoint Inhibitor, Locally Advanced Gastric Carcinoma
- What is being tested?
- FLOT combined with toripalimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 25 Jun 2021to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 70 ≥ Age ≥ 18 years regardless of gender
- Gastric adenocarcinoma confirmed by pathology
- no distant metastasis and resectable or potentially resectable evaluated by general surgery experts
- ECOG PS 0-1
- clinical stage T3/4 or N+ by AJCC 8.0
- PD-L1 CPS ≥1 (IHC 22C3 pharm Dx assay (Dako))
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- expected lifespan over 3 months
- Adequate organ function: 1) without growth factor and blood component support in the first 2 weeks of enrollment; 2) Cardiac function: no heart disease or coronary heart disease, grade 1-2; 3) liver function: TBIL ≤ 2ULN, AST ≤ 2.5 ULN, alt ≤ 2.5 ULNX 4 Renal function: cr ≤ 1.25ULN, liver function: TBIL ≤ 2ULN, TBIL ≤ 2.5ULN, alt ≤ 2.5ULN, 4)renal function: cr ≤ 1.25ULN.
- blood pressure normal or controlled within the normal range by antihypertensive drugs
- Diabetic patients were treated with hypoglycemic drugs to control fasting blood glucose ≤ 8mmol/L
- Patients with positive hepatitis B surface antigen need to be tested for quantitative detection of hepatitis B DNA virus. HBV DNA should be less than the upper limit of the normal test value for patients with HBV infection.
- no other serious diseases conflicting with this study
- No history of other malignant tumors
- Women of childbearing age must be tested negative for blood pregnancy test within 7 days before enrollment, and subjects of childbearing age must use appropriate contraceptive measures during the trial and within 6 months after the trial
- agreement to participate in this study and signed the informed consent form
Who cannot join
- Pregnant or lactating women
- Suffered from severe infectious diseases within 4 weeks before entering the group
- Bronchial asthma requires intermittent use of bronchodilators or medical intervention
- Due to the use of immunosuppressants before coexisting diseases and the dosage of immunosuppressants ≥ 10mg/, the oral dose of prednisone lasted for more than 2 weeks
- Clinically obvious cardio-cerebrovascular diseases, including, but not limited to, severe acute myocardial infarction, instability or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmias requiring medical intervention, left ventricular ejection fraction < 50%, stroke within 6 months
- Allergic to any experimental drug and its excipients, or have a history of severe allergy, or are contraindications to experimental drugs
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- Severe mental disorders
- Abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s Fib < 1.5g/L), bleeding tendency or undergoing thrombolysis or anticoagulation therapy
- Past or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, severe impairment of lung function, etc.
- Unable to swallow research drugs, chronic diarrhea (including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis) and intestinal obstruction affect drug use and absorption
- Have a history of immunodeficiency, including positive for HIV, or suffer from other acquired, congenital immunodeficiency diseases, or have a history of organ transplant
- Other researchers evaluate those who do not meet the criteria for admission
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
Zhengzhou, Henan, 450008
Quanli Gao, M.D, +86-371-65587795, gaoquanli2015@126.com
Lingdi Zhao, M.D, +86-371-65587483, lingdizhao@126.com
About this study
Official title: Toripalimab Combined With FLOT Regimen in Locally Advanced Gastric cancer-a Prospective, Open, Multi-center, Phase Ⅱ Clinical Study
Neoadjuvant chemoimmunotherapy for locally advanced gastric and gastroesophageal junction (G/GEJ) cancer is currently under investigation. Most clinical studies have simply combined chemotherapy with anti-PD-1 therapy without considering the impact of chemotherapy drugs on activated immune cells. We designed this study to explore two different treatment regimens for neoadjuvant chemotherapy in patients with locally advanced G/GEJ cancer. One group received FLOT plus toripalimab on Day 1 of each cycle, every 2 weeks for 4 cycles, followed by surgery; the other group received FLOT plus toripalimab on Day 3 of each cycle, every 3 weeks for 3 cycles, followed by surgery. A total of 69 subjects were enrolled. Preliminary statistical analysis conducted one year after the last subject was enrolled revealed no statistically significant differences in pCR and MPR between the two regimens. The median DFS for both groups has not been reached, and there is no statistically significant difference in DFS between the two groups at present. Further subgroup analysis indicated that among subjects with PD-L1 CPS ≥1, the triweekly group achieved a rate of 42.1%, compared to 29.4% in the biweekly group, with no statistically significant difference between the two groups. However, the incidence of bone marrow suppression was lower in the triweekly group than in the biweekly group. Based on the preliminary findings, we plan to conduct an expanded study and transition to a multicenter clinical trial. This study aims to further validate the efficacy of the triweekly chemoimmunotherapy in patients with PD-L1 CPS ≥1 locally advanced G/GEJ cancer.
Read the detailed description
Eligible patients received FLOT combined with toripalimab on Day 3 every 3 weeks, for a total of 3 cycles, followed by surgical treatment. Postoperative adjuvant therapy was determined based on pathological results: if a pathological complete response (pCR) was achieved, patients received 2 additional cycles of the neoadjuvant regimen; if pCR was not achieved, patients were given 4 cycles of SOX combined with toripalimab postoperatively.
- Being tested
- FLOT combined with toripalimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLOT combined with toripalimabDrug
Also called FLOT plus toripalimab
Patients received FLOT combined with toripalimab on Day 3 every 3 weeks, for a total of 3 cycles, followed by surgical treatment. Postoperative adjuvant therapy was determined based on pathological results: if a pathological complete response (pCR) was achieved, patients received 2 additional cycles of the neoadjuvant regimen; if pCR was not achieved, patients were given 4 cycles of SOX combined with toripalimab postoperatively.
| Study group | Role | What they receive |
|---|---|---|
| experimental group | Experimental | patients received FLOT regimen on day 1 and toripalimab on day 3. Receives: Drug: FLOT combined with toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological complete response rate
the proportion of patients with no tumor cells in the postoperative specimens
Measured: 6 months
Secondary outcomes (2)
rate of adverse events
rate of adverse events
Measured: 3 months
disease-free survival
the rate of patients who keep from disease at three years
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2021
- Study start25 Jun 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ChemotherapyStudies of the same condition, open and under way.
- More trials run by Henan Cancer HospitalThe 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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henan Cancer Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Quanli Gao, Henan Cancer Hospital
- Investigators
- Quanli Gao, M.D, Principal investigator, Department of Immunotherapy, Henan Provincial Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04891016
- Sponsor's protocol ID
- HenanCH immunotherapy006
- Status last verified
- Jun 2024
- First submitted
- 10 May 2021
- Last updated
- 6 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Demographic characteristics, adverse reactions, postoperative pathology
Publications
Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, Nederlof I, Kluin RJC, Warren S, Ong S, Wiersma TG, Russell NS, Lalezari F, Schouten PC, Bakker NAM, Ketelaars SLC, Peters D, Lange CAH, van Werkhoven E, van Tinteren H, Mandjes IAM, Kemper I, Onderwater S, Chalabi M, Wilgenhof S, Haanen JBAG, Salgado R, de Visser KE, Sonke GS, Wessels LFA, Linn SC, Schumacher TN, Blank CU, Kok M. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019 Jun;25(6):920-928. doi: 10.1038/s41591-019-0432-4. Epub 2019 May 13.
PubMed 31086347Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, von Minckwitz G, Thomalla J, Kummel S, Rautenberg B, Fasching PA, Weber K, Rhiem K, Denkert C, Schneeweiss A. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019 Aug 1;30(8):1279-1288. doi: 10.1093/annonc/mdz158.
PubMed 31095287He X, Du Y, Wang Z, Wang X, Duan J, Wan R, Xu J, Zhang P, Wang D, Tian Y, Han J, Fei K, Bai H, Tian J, Wang J. Upfront dose-reduced chemotherapy synergizes with immunotherapy to optimize chemoimmunotherapy in squamous cell lung carcinoma. J Immunother Cancer. 2020 Oct;8(2):e000807. doi: 10.1136/jitc-2020-000807.
PubMed 33115941Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M, Yasui H, Yabusaki H, Afanasyev S, Park YK, Al-Batran SE, Yoshikawa T, Yanez P, Dib Bartolomeo M, Lonardi S, Tabernero J, Van Cutsem E, Janjigian YY, Oh DY, Xu J, Fang X, Shih CS, Bhagia P, Bang YJ; KEYNOTE-585 investigators. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024 Feb;25(2):212-224. doi: 10.1016/S1470-2045(23)00541-7. Epub 2023 Dec 19.
PubMed 38134948
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Toripalimab Combined With FLOT Regimen in Locally Advanced Gastric cancer-a Prospective, Open, Multi-center, Phase Ⅱ Clinical Study
- ClinicalTrials.gov ID
- NCT04891016
- Acronym / sponsor ID
- HenanCH immunotherapy006
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Henan Cancer HospitalOther government
- Study start
- 25 Jun 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 18 May 2021 (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.
Neoadjuvant chemoimmunotherapy for locally advanced gastric and gastroesophageal junction (G/GEJ) cancer is currently under investigation. Most clinical studies have simply combined chemotherapy with anti-PD-1 therapy without considering the impact of chemotherapy drugs on activated immune cells. We designed this study to explore two different treatment regimens for neoadjuvant chemotherapy in patients with locally advanced G/GEJ cancer. One group received FLOT plus toripalimab on Day 1 of each cycle, every 2 weeks for 4 cycles, followed by surgery; the other group received FLOT plus toripalimab on Day 3 of each cycle, every 3 weeks for 3 cycles, followed by surgery. A total of 69 subjects were enrolled. Preliminary statistical analysis conducted one year after the last subject was enrolled revealed no statistically significant differences in pCR and MPR between the two regimens. The median DFS for both groups has not been reached, and there is no statistically significant difference in DFS between the two groups at present. Further subgroup analysis indicated that among subjects with PD-L1 CPS ≥1, the triweekly group achieved a rate of 42.1%, compared to 29.4% in the biweekly group, with no statistically significant difference between the two groups. However, the incidence of bone marrow suppression was lower in the triweekly group than in the biweekly group. Based on the preliminary findings, we plan to conduct an expanded study and transition to a multicenter clinical trial. This study aims to further validate the efficacy of the triweekly chemoimmunotherapy in patients with PD-L1 CPS ≥1 locally advanced G/GEJ cancer.
Detailed description
Eligible patients received FLOT combined with toripalimab on Day 3 every 3 weeks, for a total of 3 cycles, followed by surgical treatment. Postoperative adjuvant therapy was determined based on pathological results: if a pathological complete response (pCR) was achieved, patients received 2 additional cycles of the neoadjuvant regimen; if pCR was not achieved, patients were given 4 cycles of SOX combined with toripalimab postoperatively.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| experimental group | Experimental | Drug: FLOT combined with toripalimabpatients received FLOT regimen on day 1 and toripalimab on day 3. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 70 ≥ Age ≥ 18 years regardless of gender
- Gastric adenocarcinoma confirmed by pathology
- no distant metastasis and resectable or potentially resectable evaluated by general surgery experts
- ECOG PS 0-1
- clinical stage T3/4 or N+ by AJCC 8.0
Key exclusion criteria (12 listed)
- Pregnant or lactating women
- Suffered from severe infectious diseases within 4 weeks before entering the group
- Bronchial asthma requires intermittent use of bronchodilators or medical intervention
- Due to the use of immunosuppressants before coexisting diseases and the dosage of immunosuppressants ≥ 10mg/, the oral dose of prednisone lasted for more than 2 weeks
- Clinically obvious cardio-cerebrovascular diseases, including, but not limited to, severe acute myocardial infarction, instability or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmias requiring medical intervention, left ventricular ejection fraction < 50%, stroke within 6 months
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 |
|---|---|---|
| FLOT combined with toripalimabAlso: FLOT plus toripalimabPatients received FLOT combined with toripalimab on Day 3 every 3 weeks, for a total of 3 cycles, followed by surgical treatment. Postoperative adjuvant therapy was determined based on pathological results: if a pathological complete response (pCR) was achieved, patients received 2 additional cycles of the neoadjuvant regimen; if pCR was not achieved, patients were given 4 cycles of SOX combined with toripalimab postoperatively. | Drug | experimental group |
Primary outcome
pathological complete response rate
Time frame: 6 months
the proportion of patients with no tumor cells in the postoperative specimens
2 secondary outcomes
rate of adverse events
Time frame: 3 months
disease-free survival
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Background: PubMed 31086347Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, Nederlof I, Kluin RJC, Warren S, Ong S, Wiersma TG, Russell NS, Lalezari F, Schouten PC, Bakker NAM, Ketelaars SLC, Peters D, Lange CAH, van Werkhoven E, van Tinteren H, Mandjes IAM, Kemper I, Onderwater S, Chalabi M, Wilgenhof S, Haanen JBAG, Salgado R, de Visser KE, Sonke GS, Wessels LFA, Linn SC, Schumacher TN, Blank CU, Kok M. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019 Jun;25(6):920-928. doi: 10.1038/s41591-019-0432-4. Epub 2019 May 13.
- Background: PubMed 31095287Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, von Minckwitz G, Thomalla J, Kummel S, Rautenberg B, Fasching PA, Weber K, Rhiem K, Denkert C, Schneeweiss A. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019 Aug 1;30(8):1279-1288. doi: 10.1093/annonc/mdz158.
- Background: PubMed 33115941He X, Du Y, Wang Z, Wang X, Duan J, Wan R, Xu J, Zhang P, Wang D, Tian Y, Han J, Fei K, Bai H, Tian J, Wang J. Upfront dose-reduced chemotherapy synergizes with immunotherapy to optimize chemoimmunotherapy in squamous cell lung carcinoma. J Immunother Cancer. 2020 Oct;8(2):e000807. doi: 10.1136/jitc-2020-000807.
- Background: PubMed 38134948Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M, Yasui H, Yabusaki H, Afanasyev S, Park YK, Al-Batran SE, Yoshikawa T, Yanez P, Dib Bartolomeo M, Lonardi S, Tabernero J, Van Cutsem E, Janjigian YY, Oh DY, Xu J, Fang X, Shih CS, Bhagia P, Bang YJ; KEYNOTE-585 investigators. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024 Feb;25(2):212-224. doi: 10.1016/S1470-2045(23)00541-7. Epub 2023 Dec 19.
- Individual participant dataSharing planned: Yes. Demographic characteristics, adverse reactions, postoperative pathology
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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.
Quanli Gao, M.D principal investigator
Department of Immunotherapy, Henan Provincial Cancer Hospital
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 FLOT combined with toripalimab in people with Chemotherapy and Immune Checkpoint Inhibitor, run by Henan Cancer Hospital 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 15 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 6 Jun 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Quanli Gao, M.D (+8637165587483, gaoquanli2015@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological complete response rate (time frame: 6 months). 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 NCT04891016, which also lists 4 linked publications.
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 6 Jun 2024.