Gastroesophageal Junction CancerPhase 3NCT06411171
Safety and Efficacy of Pembrolizumab in Combination With FLOT About Gastroesophageal Junction Cancer:
A Phase 3 study testing Pembrolizumab plus chemotherapy (FLOT) in people with Gastroesophageal Junction Cancer, run by xiaohua li.
Trial summary
At present, surgery is still the main treatment for gastroesophageal junction cancer. At the same time, multimodal comprehensive treatment such as chemotherapy and molecular targeted therapy can effectively alleviate pathological progression, facilitate R0 resection and improve the overall survival of… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gastroesophageal Junction Cancer
- What is being tested?
- Pembrolizumab plus chemotherapy (FLOT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2024to 1 Sep 2028
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) aged from 18 to 75 years old, including 18 and 80 years old;
- 2) histologically or cytologically confirmed locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma;
- 3) ECOG PS score 0 or 1;
- 4) Known PD-L1 expression (assessed centrally using PD-L1 HC22C3)
- 5) no previous treatment
- 6) HER2-negative status
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- 7) normal hematological parameters: white blood cell count ≥4×109/L; Absolute neutrophil count ≥1.5×109/L; Platelet count ≥100×109/L; Blood red protein g/L;
- 8) basically normal renal function: serum creatinine ≤1.5×ULN or creatinine clearance (CrCl)\> 60 mL/min(using Cockcroft-Gault formula):
- Female CrCl=(140-age)× weight (kg)× 0.85 / (72×Scr mg/dl)
- Male CrCl=(140-age)× weight (kg)× 1.00 / (72×Scr mg/dl)
- Liver function was basically normal: serum total bilirubin ≤1.5×ULN; Aspartate aminotransferase (AST) ≤2.5×ULN; Alanine aminotransferase (ALT) ≤2.5×ULN.
- Female patients must have a negative urine pregnancy test before the start of the study (not applicable to patients with bilateral oophorectomy and/or hysterectomy or postmenopausal patients)
- 9) Provide written informed consent. Written informed consent was obtained.
Who cannot join
- 1) receiving anti-tumor therapy before enrollment, including but not limited to PD-1 inhibitors, CTLA-4 antibodies, EGFR monoclonal antibodies, EGFR-Tkis, and anti-angiogenic drugs;
- 2) A history of autoimmune disease, including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. (Note: Patients with vitiligo, type I diabetes, or residual hypothyroidism due to autoimmune conditions (e.g., after Hashimoto's syndrome) requiring only hormone-replacement therapy, psoriasis requiring no systemic therapy, or if recurrence was not expected in the absence of an external trigger were allowed.) ;
- 3) participated in other interventional clinical trials within 30 days before screening;
- 4) Patients with a history of other malignant tumors (except cured basal cell carcinoma)
- 5) with severe uncontrolled comorbidities (e.g., heart failure, diabetes mellitus, hypertension, liver failure, renal failure, thyroid disease, mental illness, etc.);
- 6) known HIV infection or active viral hepatitis or tuberculosis;
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- 7) have a major surgical procedure or planned surgery within 30 days before the first dose of the trial drug;
- 8) patients who are allergic to the drugs used in this regimen or their components;
- 9) pregnant (confirmed by blood or urine HCG testing) or lactating women, or childbearing age subjects unwilling or unable to use effective contraception (for both male and female subjects) until at least 6 months after the last trial treatment;
- 10) The investigator considers that it is not appropriate to participate in the study;
- 11) unwilling to participate in the study or unable to sign an informed consent form
About this study
Official title: Safety and Efficacy of Pembrolizumab in Combination With FLOT as a First-line Treatment in Patients With Gastroesophageal Junction Cancer: a Prospective Multicenter Randomized Controlled Trial
At present, surgery is still the main treatment for gastroesophageal junction cancer. At the same time, multimodal comprehensive treatment such as chemotherapy and molecular targeted therapy can effectively alleviate pathological progression, facilitate R0 resection and improve the overall survival of patients.Pembrolizumab, as a PD-1 inhibitor, has been shown to have antitumor activity and a manageable safety profile in gastroesophageal junction cancer.Pembrolizumab combined with chemotherapy has become a research hotspot. However, to date, there is no clinical study related to gastroesophageal junction cancer. In this study, Pembrolizumab combined with FLOT was used as the first-line treatment for gastroesophageal junction cancer, aiming to explore the experience chemotherapy mode for gastroesophageal junction cancer.
Read the detailed description
Gastric cancer, including gastroesophageal junction cancer, is the fifth most common cancer and the third leading cause of death in the world. Among them, although the incidence of distal gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction cancer is increasing. At present, surgery is still the main treatment for gastroesophageal junction cancer. At the same time, multi-mode comprehensive treatment such as chemotherapy and molecular targeted therapy can effectively alleviate pathological progression, facilitate R0 resection and improve the overall survival of patients. A large number of previous clinical trials on the combination of first-line chemotherapy and molecular targeted drugs in the treatment of gastric and gastroesophageal junction cancer have shown that only trastuzumab can improve the overall survival rate of Her-2 positive patients. In addition, despite various clinical chemotherapy regimens, the median survival time of gastric cancer and gastroesophageal junction cancer is not high. Therefore, the treatment mode of gastroesophageal junction cancer, especially for Her-2 negative patients, needs to be explored and improved.
In recent years, immune checkpoint inhibitors represented by programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors have been applied to the treatment of a variety of solid tumors such as melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, and urothelial cancer. It has become another important treatment strategy after surgery, chemotherapy, radiotherapy and targeted therapy. Studies have shown that PD-L1 is highly expressed in tumor cells and immune cells in gastric cancer and gastroesophageal junction cancer and plays a key role in tumor immune escape, therefore, the PD-1/ PD-L1 pathway will become an important target for effective intervention in gastroesophageal junction cancer. As a PD-1 inhibitor, Pembrolizumab has been shown to have anti-tumor activity and manageable safety in gastroesophageal junction cancer, and was approved by the US FDA in September 2017 for advanced PD-L1-positive gastric or gastroesophageal junction cancer . The phase Ⅱ KEYNOTE-059 trial used Pembrolizumab as a single agent in the third-line treatment of advanced gastric or gastroesophageal junction cancer, and the results showed that it had controllable safety in patients with PD-L1 positive, with obvious advantages in objective response rate (ORR) and median duration of response (DOR) [12]. Chemotherapy enhances tumor immune responses by enhancing tumor cell immunogenicity and sensitivity to immune killing, and the combination of chemotherapy and immune checkpoint inhibitors has been shown to improve overall survival in several cancer types. Therefore, PD-1/ PD-L1 immunosuppressant combined with chemotherapy has become a hot spot in the research of advanced gastric cancer or gastroesophageal junction cancer . The phase 3 KEYNOTE-062 trial compared Pembrolizumab plus chemotherapy (cisplatin plus 5-FU or capecitabine) with chemotherapy alone or Pembrolizumab alone in the first-line treatment of advanced gastric or gastroesophageal junction cancer. However, compared with chemotherapy alone, Pembrolizumab combined with chemotherapy could not significantly prolong the overall survival of patients, and the overall effect was not better than chemotherapy alone . In contrast, the phase III KEYNOTE-590 study, designed to compare the efficacy and safety of Pembrolizumab plus chemotherapy (cisplatin plus fluorouracil) versus chemotherapy alone as first-line treatment for advanced esophageal and Siwert type I gastroesophageal junction cancer, showed that Pembrolizumab combined with chemotherapy was significantly superior to chemotherapy alone . Neither the KEYNOTE-062 trial nor the KEYNOTE-590 trial analyzed a separate population of patients with gastroesophageal junction cancer, and there are some differences in response to drugs by tissue type. Therefore, The efficacy of Pembrolizumab plus chemotherapy in the only patient population with gastroesophageal junction cancer warrants further investigation.
- Conditions
- Gastroesophageal Junction Cancer
- Being tested
- Pembrolizumab plus chemotherapy (FLOT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab plus chemotherapy (FLOT)Drug
Also called docetaxel, oxaliplatin, fluorouracil, and leucovorin (the FLOT regimen)
The experimental group was treated with pembrolizumab combined with FLOT, and the control group was treated with FLOT chemotherapy alone
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab plus chemotherapy (FLOT) | Experimental | Pembrolizumab plus chemotherapy (FLOT) Receives: Drug: Pembrolizumab plus chemotherapy (FLOT) |
| chemotherapy (FLOT) | Active comparator | chemotherapy (FLOT) Receives: Drug: Pembrolizumab plus chemotherapy (FLOT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate
objective response rate
Measured: 3 year
Secondary outcomes (4)
duration of response
duration of response
Measured: 1 year
disease control rate
disease control rate
Measured: 1 year
time to response
time to response
Measured: 1 year
overall surival
overall surival
Measured: 5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2024
- Study start1 Jun 2024 (estimated)
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastroesophageal Junction 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- xiaohua li
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, xiaohua li, Xijing Hospital of Digestive Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06411171
- Sponsor's protocol ID
- KY20232301-F-1
- Status last verified
- May 2024
- First submitted
- 7 May 2024
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Pembrolizumab in Combination With FLOT as a First-line Treatment in Patients With Gastroesophageal Junction Cancer: a Prospective Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06411171
- Acronym / sponsor ID
- KY20232301-F-1
- Conditions
- Gastroesophageal Junction Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- xiaohua liUniversity, hospital or other
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 13 May 2024 (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.
At present, surgery is still the main treatment for gastroesophageal junction cancer. At the same time, multimodal comprehensive treatment such as chemotherapy and molecular targeted therapy can effectively alleviate pathological progression, facilitate R0 resection and improve the overall survival of patients.Pembrolizumab, as a PD-1 inhibitor, has been shown to have antitumor activity and a manageable safety profile in gastroesophageal junction cancer.Pembrolizumab combined with chemotherapy has become a research hotspot. However, to date, there is no clinical study related to gastroesophageal junction cancer. In this study, Pembrolizumab combined with FLOT was used as the first-line treatment for gastroesophageal junction cancer, aiming to explore the experience chemotherapy mode for gastroesophageal junction cancer.
Detailed description
Gastric cancer, including gastroesophageal junction cancer, is the fifth most common cancer and the third leading cause of death in the world. Among them, although the incidence of distal gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction cancer is increasing. At present, surgery is still the main treatment for gastroesophageal junction cancer. At the same time, multi-mode comprehensive treatment such as chemotherapy and molecular targeted therapy can effectively alleviate pathological progression, facilitate R0 resection and improve the overall survival of patients. A large number of previous clinical trials on the combination of first-line chemotherapy and molecular targeted drugs in the treatment of gastric and gastroesophageal junction cancer have shown that only trastuzumab can improve the overall survival rate of Her-2 positive patients. In addition, despite various clinical chemotherapy regimens, the median survival time of gastric cancer and gastroesophageal junction cancer is not high. Therefore, the treatment mode of gastroesophageal junction cancer, especially for Her-2 negative patients, needs to be explored and improved.
In recent years, immune checkpoint inhibitors represented by programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors have been applied to the treatment of a variety of solid tumors such as melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, and urothelial cancer. It has become another important treatment strategy after surgery, chemotherapy, radiotherapy and targeted therapy. Studies have shown that PD-L1 is highly expressed in tumor cells and immune cells in gastric cancer and gastroesophageal junction cancer and plays a key role in tumor immune escape, therefore, the PD-1/ PD-L1 pathway will become an important target for effective intervention in gastroesophageal junction cancer. As a PD-1 inhibitor, Pembrolizumab has been shown to have anti-tumor activity and manageable safety in gastroesophageal junction cancer, and was approved by the US FDA in September 2017 for advanced PD-L1-positive gastric or gastroesophageal junction cancer . The phase Ⅱ KEYNOTE-059 trial used Pembrolizumab as a single agent in the third-line treatment of advanced gastric or gastroesophageal junction cancer, and the results showed that it had controllable safety in patients with PD-L1 positive, with obvious advantages in objective response rate (ORR) and median duration of response (DOR) [12]. Chemotherapy enhances tumor immune responses by enhancing tumor cell immunogenicity and sensitivity to immune killing, and the combination of chemotherapy and immune checkpoint inhibitors has been shown to improve overall survival in several cancer types. Therefore, PD-1/ PD-L1 immunosuppressant combined with chemotherapy has become a hot spot in the research of advanced gastric cancer or gastroesophageal junction cancer . The phase 3 KEYNOTE-062 trial compared Pembrolizumab plus chemotherapy (cisplatin plus 5-FU or capecitabine) with chemotherapy alone or Pembrolizumab alone in the first-line treatment of advanced gastric or gastroesophageal junction cancer. However, compared with chemotherapy alone, Pembrolizumab combined with chemotherapy could not significantly prolong the overall survival of patients, and the overall effect was not better than chemotherapy alone . In contrast, the phase III KEYNOTE-590 study, designed to compare the efficacy and safety of Pembrolizumab plus chemotherapy (cisplatin plus fluorouracil) versus chemotherapy alone as first-line treatment for advanced esophageal and Siwert type I gastroesophageal junction cancer, showed that Pembrolizumab combined with chemotherapy was significantly superior to chemotherapy alone . Neither the KEYNOTE-062 trial nor the KEYNOTE-590 trial analyzed a separate population of patients with gastroesophageal junction cancer, and there are some differences in response to drugs by tissue type. Therefore, The efficacy of Pembrolizumab plus chemotherapy in the only patient population with gastroesophageal junction cancer warrants further investigation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab plus chemotherapy (FLOT) | Experimental | Drug: Pembrolizumab plus chemotherapy (FLOT)Pembrolizumab plus chemotherapy (FLOT) |
| chemotherapy (FLOT) | Active comparator | Drug: Pembrolizumab plus chemotherapy (FLOT)chemotherapy (FLOT) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 1) aged from 18 to 75 years old, including 18 and 80 years old;
- 2) histologically or cytologically confirmed locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma;
- 3) ECOG PS score 0 or 1;
- 4) Known PD-L1 expression (assessed centrally using PD-L1 HC22C3)
- 5) no previous treatment
Key exclusion criteria (11 listed)
- 1) receiving anti-tumor therapy before enrollment, including but not limited to PD-1 inhibitors, CTLA-4 antibodies, EGFR monoclonal antibodies, EGFR-Tkis, and anti-angiogenic drugs;
- 2) A history of autoimmune disease, including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. (Note: Patients with vitiligo, type I diabetes, or residual hypothyroidism due to autoimmune conditions (e.g., after Hashimoto's syndrome) requiring only hormone-replacement therapy, psoriasis requiring no systemic therapy, or if recurrence was not expected in the absence of an external trigger were allowed.) ;
- 3) participated in other interventional clinical trials within 30 days before screening;
- 4) Patients with a history of other malignant tumors (except cured basal cell carcinoma)
- 5) with severe uncontrolled comorbidities (e.g., heart failure, diabetes mellitus, hypertension, liver failure, renal failure, thyroid disease, mental illness, etc.);
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 |
|---|---|---|
| Pembrolizumab plus chemotherapy (FLOT)Also: docetaxel, oxaliplatin, fluorouracil, and leucovorin (the FLOT regimen)The experimental group was treated with pembrolizumab combined with FLOT, and the control group was treated with FLOT chemotherapy alone | Drug | Pembrolizumab plus chemotherapy (FLOT), chemotherapy (FLOT) |
Primary outcome
objective response rate
Time frame: 3 year
objective response rate
4 secondary outcomes
duration of response
Time frame: 1 year
disease control rate
Time frame: 1 year
time to response
Time frame: 1 year
overall surival
Time frame: 5 year
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 17 May 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pembrolizumab plus chemotherapy (FLOT) in people with Gastroesophageal Junction Cancer, run by xiaohua li.
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 13 inclusion and 11 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: opening soon, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
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?
objective response rate (time frame: 3 year). 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 17 May 2024.