Gastroesophageal AdenocarcinomaPhase 1/2SCORPIONCT05986227
The Sequential Combination of FOLFOX and Toripalimab for Perioperative Immuno-Oncology Therapy of HER2-negative Adenocarcinoma of the Esophagogastric Junction (Siewert I/II):
A Phase 1/2 study testing toripalimab FOLFOX in people with Gastroesophageal Adenocarcinoma, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.
Trial summary
The addition of immunotherapy to chemotherapy improves outcomes in patients with HER2-negative gastroesophageal adenocarcinoma (GEA), and investigators aim to explore its role in the perioperative setting. Moreover, optimizing the timing schedule of these two therapies is critical when balancing efficacy and safety. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gastroesophageal Adenocarcinoma
- What is being tested?
- toripalimab FOLFOX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2023to 1 Jul 2026
- Phase
- Phase 1/2
- 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
- Age >/= 18 years;
- Male or Female;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
- Histologically or cytologically confirmed locally advanced adenocarcinoma of esophagus or gastroesophageal junction (Siewert type I/II);
- Human epidermal growth factor receptor 2 (HER2)-negative tumors;
- Clinical staging cT2-T4aNanyM0 or TanyN+M0 (UICC/AJCC 8th edition), potentially resectable disease;
Show all 9Show fewer
- Adequate hematologic and end organ function based on laboratory results obtained within 14 days prior to initiation of study treatment;
- For women of childbearing potential: agreement to remain abstinent；no evidence of pregnancy within 72 hours before the start of study regimen;
- Must be willing and able to provide written informed consent.
Who cannot join
- Known unresectable disease，cT4b disease invading aorta or trachea;
- Known distant metastases，including supraclavicular lymph nodal disease；
- Uncontrollable pleural or pericardial effusion，or ascites requiring repeated interventions;
- Prior chemotherapy, immunotherapy, targeted therapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor;
- Poor nutritional status, BMI < 18.5 Kg/m2; if symptomatic nutritional support is corrected before randomization, enrollment may continue to be considered after assessment by the principal investigator;
- History of allergy to biological drugs produced by Chinese hamster ovary cells, any component of toripalimab, tegafur, oxaliplatin or other platinum drugs;
Show all 23Show fewer
- History of severe allergic, allergic reactions, or other hypersensitivity to chimeric or humanized antibodies or fusion proteins;
- Patients with prior malignancies are eligible if they have been disease-free for > 5 years and are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years prior to enrollment；
- History of any active autoimmune disease or autoimmune disease, including 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, glomerulonephritis, etc.; hypothyroidism (hormone replacement therapy can be considered to be included);
- History of immunosuppressive drugs, or systemic hormones used to achieve immunosuppressive purposes (dose > 10 mg/day prednisone or equivalent dose) within 2 weeks before the first use of the study drug; in the absence of active autoimmune diseases, inhaled or local steroids are allowed and doses > 10 mg/day prednisone or equivalent doses of adrenocorticotropic hormone replacement;
- History of type 1 diabetes, whose blood glucose is controlled after treatment with a stable dose of insulin dosing regimen may be enrolled in this study;
- History of live attenuated vaccines are received within 4 weeks before the first use of the study drug;
- History of major surgery or severe trauma within 4 weeks before the first use of the study drug;
- History of eczema, psoriasis, lichen simplex chronicus, or dermatologic manifestations of vitiligo (eg, patients with psoriatic arthritis were excluded from the study) were permitted to enroll in this study if they met the following conditions: a) had rash coverage less than 10% of body surface area (BSA); b) had adequately controlled disease at baseline and required only low-potency topical steroid therapy; c) did not have an acute exacerbation of the underlying disease within the past 12 months without the need for PUVA (psoralen plus ultraviolet A radiation), methotrexate, retinoids, biologics, oral calcineurin inhibitors, high-titer, or oral steroid therapy for]；
- History of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, interstitial pneumonia, or evidence of active pneumonia on screening chest CT scan;
- History of immunodeficiency, including HIV test positive, or suffering from other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation;
- Uncontrolled cardiac clinical symptoms or diseases, including but not limited to: a) NYHA class II or higher heart failure; b) unstable angina; c) myocardial infarction within 1 year; d) clinically significant supraventricular or ventricular arrhythmia that remains poorly controlled without or after clinical intervention.
- Known hereditary or acquired bleeding and thrombophilia (such as hemophilia, coagulation dysfunction, thrombocytopenia, etc.);
- Known serious infection (CTCAE > 2) within 4 weeks before the first use of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; baseline chest imaging showed active pulmonary inflammation, symptoms and signs of infection within 14 days before the first use of the study drug or oral or intravenous antibiotics, except for the prophylactic use of antibiotics;
- Active pulmonary tuberculosis infection detected by medical history or CT examination, or history of active pulmonary tuberculosis infection within 1 year before enrollment, or history of active pulmonary tuberculosis infection more than 1 year ago but without regular treatment;
- Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive, and HCV RNA above the lower limit of detection of the analytical method);
- Pregnant or lactating women;
- Other factors that may lead to forced halfway termination of the study as judged by the investigator, such as having other serious diseases (including mental illness) requiring concomitant treatment, alcoholism, drug abuse, family or social factors that may affect the safety or compliance of the subject.
About this study
Official title: The Sequential Combination of FOLFOX and Toripalimab for Perioperative Immuno-oncology Therapy of HER2-negative Gastroesophageal Adenocarcinoma (Siewert I/II): a Multicenter, Open-label, Randomized Controlled, Phase 1b/2 Trial (SCORPIO/NCCES05)
The addition of immunotherapy to chemotherapy improves outcomes in patients with HER2-negative gastroesophageal adenocarcinoma (GEA), and investigators aim to explore its role in the perioperative setting. Moreover, optimizing the timing schedule of these two therapies is critical when balancing efficacy and safety. This Chinese, multicenter, open-label phase 1b/2 trial will evaluate the efficacy and toxicity of perioperative folinic acid, fluoro-uracil, oxali-platin (FOLFOX), and toripalimab (JS001, a novel PD-1 inhibitor) in combination at various schedules in the neoadjuvant setting in patients with HER2-negative resectable GEA: three cycles each in Arm A: FOLFOX (D1, q2w) followed by toripalimab (D3, 3 mg/kg, q2w); Arm B: concurrent FOLFOX (D1, q2w) combined with toripalimab (D1, 3 mg/kg, q2w); Arm C: toripalimab (D1, 3 mg/kg, q2w) followed by FOLFOX (D3, q2w); Arm D: FOLFOX (D1, q2w) alone. The primary end-point is the dose-limiting toxicity in Phase 1b and the pathological complete response rate in Phase 2; secondary end-points include major pathologic response, disease-free survival, and event-free survival.A fixed sample size of 126 patients is used in this study, with a safety run-in period (n = 6) and cohort expansion period (n = 24), a dropout rate of 5% within 12 months of follow-up. Each arm receives three cycles of FOLFOX (D1, q2w) followed by 15 cycles of toripalimab (D1, 240 mg, q3w) in the neoadjuvant setting. Pre-treatment biopsies, post-resection specimens, serial liquid biopsy, and gut microbiota samples on treatment will be collected to explore the biomarkers' predictive value on diverse schedule efficacy and safety.
Read the detailed description
This Chinese, multicenter, open-label phase 1b/2 trial will evaluate the efficacy and toxicity of perioperative folinic acid, fluoro-uracil, oxali-platin (FOLFOX), and toripalimab (JS001, a novel PD-1 inhibitor) in combination at various schedules in the neoadjuvant setting in patients with HER2-negative resectable GEA: three cycles each in Arm A: FOLFOX (D1, q2w) followed by toripalimab (D3, 3 mg/kg, q2w); Arm B: concurrent FOLFOX (D1, q2w) combined with toripalimab (D1, 3 mg/kg, q2w); Arm C: toripalimab (D1, 3 mg/kg, q2w) followed by FOLFOX (D3, q2w); Arm D: FOLFOX (D1, q2w) alone. The primary end-point is the dose-limiting toxicity in Phase 1b and the pathological complete response rate in Phase 2; secondary end-points include major pathologic response, disease-free survival, and event-free survival. A fixed sample size of 126 patients is used in this study, with a safety run-in period (n = 6) and cohort expansion period (n = 24), a dropout rate of 5% within 12 months of follow-up. Each arm receives three cycles of FOLFOX (D1, q2w) followed by 15 cycles of toripalimab (D1, 240 mg, q3w) in the neoadjuvant setting. Pre-treatment biopsies, post-resection specimens, serial liquid biopsy, and gut microbiota samples on treatment will be collected to explore the biomarkers' predictive value on diverse schedule efficacy and safety.
- Conditions
- Gastroesophageal Adenocarcinoma
- Being tested
- toripalimab FOLFOX
- Keywords
- GEA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
toripalimab FOLFOXDrug
Toripalimab（3mg/kg, q2w, IV）oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV) and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h)
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX(D1)was combined with toripalimab(D3) | Experimental | Not described Receives: Drug: toripalimab FOLFOX |
| FOLFOX(D1)was combined with toripalimab(D1) | Experimental | Not described Receives: Drug: toripalimab FOLFOX |
| FOLFOX(D3) was combined with toripalimab(D1) | Experimental | Not described Receives: Drug: toripalimab FOLFOX |
| FOLFOX(D1) | Active comparator | Not described Receives: Drug: toripalimab FOLFOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Phase 1b: safety of the combination regimen in different drug treatment sequences, i.e., dose-limiting toxicity (DLT).
Measured: through study completion,an average of 1.5 years
PCR
Phase II: efficacy of different sequential combinations of drugs, i.e., postoperative pathological complete response rate (pCR).
Measured: 0.5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start1 Aug 2023 (estimated)
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastroesophageal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05986227
- Sponsor's protocol ID
- 2022111621481500
- Acronym
- SCORPIO
- Status last verified
- Nov 2022
- First submitted
- 30 Apr 2023
- Last updated
- 14 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Sequential Combination of FOLFOX and Toripalimab for Perioperative Immuno-oncology Therapy of HER2-negative Gastroesophageal Adenocarcinoma (Siewert I/II): a Multicenter, Open-label, Randomized Controlled, Phase 1b/2 Trial (SCORPIO/NCCES05)
- ClinicalTrials.gov ID
- NCT05986227
- Acronym / sponsor ID
- SCORPIO / 2022111621481500
- Conditions
- Gastroesophageal Adenocarcinoma
- Keywords
- GEA
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 1 Aug 2023 (estimated)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 14 Aug 2023 (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 addition of immunotherapy to chemotherapy improves outcomes in patients with HER2-negative gastroesophageal adenocarcinoma (GEA), and investigators aim to explore its role in the perioperative setting. Moreover, optimizing the timing schedule of these two therapies is critical when balancing efficacy and safety. This Chinese, multicenter, open-label phase 1b/2 trial will evaluate the efficacy and toxicity of perioperative folinic acid, fluoro-uracil, oxali-platin (FOLFOX), and toripalimab (JS001, a novel PD-1 inhibitor) in combination at various schedules in the neoadjuvant setting in patients with HER2-negative resectable GEA: three cycles each in Arm A: FOLFOX (D1, q2w) followed by toripalimab (D3, 3 mg/kg, q2w); Arm B: concurrent FOLFOX (D1, q2w) combined with toripalimab (D1, 3 mg/kg, q2w); Arm C: toripalimab (D1, 3 mg/kg, q2w) followed by FOLFOX (D3, q2w); Arm D: FOLFOX (D1, q2w) alone. The primary end-point is the dose-limiting toxicity in Phase 1b and the pathological complete response rate in Phase 2; secondary end-points include major pathologic response, disease-free survival, and event-free survival.A fixed sample size of 126 patients is used in this study, with a safety run-in period (n = 6) and cohort expansion period (n = 24), a dropout rate of 5% within 12 months of follow-up. Each arm receives three cycles of FOLFOX (D1, q2w) followed by 15 cycles of toripalimab (D1, 240 mg, q3w) in the neoadjuvant setting. Pre-treatment biopsies, post-resection specimens, serial liquid biopsy, and gut microbiota samples on treatment will be collected to explore the biomarkers' predictive value on diverse schedule efficacy and safety.
Detailed description
This Chinese, multicenter, open-label phase 1b/2 trial will evaluate the efficacy and toxicity of perioperative folinic acid, fluoro-uracil, oxali-platin (FOLFOX), and toripalimab (JS001, a novel PD-1 inhibitor) in combination at various schedules in the neoadjuvant setting in patients with HER2-negative resectable GEA: three cycles each in Arm A: FOLFOX (D1, q2w) followed by toripalimab (D3, 3 mg/kg, q2w); Arm B: concurrent FOLFOX (D1, q2w) combined with toripalimab (D1, 3 mg/kg, q2w); Arm C: toripalimab (D1, 3 mg/kg, q2w) followed by FOLFOX (D3, q2w); Arm D: FOLFOX (D1, q2w) alone. The primary end-point is the dose-limiting toxicity in Phase 1b and the pathological complete response rate in Phase 2; secondary end-points include major pathologic response, disease-free survival, and event-free survival. A fixed sample size of 126 patients is used in this study, with a safety run-in period (n = 6) and cohort expansion period (n = 24), a dropout rate of 5% within 12 months of follow-up. Each arm receives three cycles of FOLFOX (D1, q2w) followed by 15 cycles of toripalimab (D1, 240 mg, q3w) in the neoadjuvant setting. Pre-treatment biopsies, post-resection specimens, serial liquid biopsy, and gut microbiota samples on treatment will be collected to explore the biomarkers' predictive value on diverse schedule efficacy and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| FOLFOX(D1)was combined with toripalimab(D3) | Experimental | Drug: toripalimab FOLFOX |
| FOLFOX(D1)was combined with toripalimab(D1) | Experimental | Drug: toripalimab FOLFOX |
| FOLFOX(D3) was combined with toripalimab(D1) | Experimental | Drug: toripalimab FOLFOX |
| FOLFOX(D1) | Active comparator | Drug: toripalimab FOLFOX |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age >/= 18 years;
- Male or Female;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
- Histologically or cytologically confirmed locally advanced adenocarcinoma of esophagus or gastroesophageal junction (Siewert type I/II);
- Human epidermal growth factor receptor 2 (HER2)-negative tumors;
Key exclusion criteria (23 listed)
- Known unresectable disease，cT4b disease invading aorta or trachea;
- Known distant metastases，including supraclavicular lymph nodal disease；
- Uncontrollable pleural or pericardial effusion，or ascites requiring repeated interventions;
- Prior chemotherapy, immunotherapy, targeted therapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor;
- Poor nutritional status, BMI < 18.5 Kg/m2; if symptomatic nutritional support is corrected before randomization, enrollment may continue to be considered after assessment by the principal investigator;
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 |
|---|---|---|
| toripalimab FOLFOXToripalimab（3mg/kg, q2w, IV）oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV) and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h) | Drug | FOLFOX(D1), FOLFOX(D1)was combined with toripalimab(D1), FOLFOX(D1)was combined with toripalimab(D3), FOLFOX(D3) was combined with toripalimab(D1) |
Primary outcome
DLT
Time frame: through study completion,an average of 1.5 years
Phase 1b: safety of the combination regimen in different drug treatment sequences, i.e., dose-limiting toxicity (DLT).
PCR
Time frame: 0.5 year
Phase II: efficacy of different sequential combinations of drugs, i.e., postoperative pathological complete response rate (pCR).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
Related trials for Gastroesophageal Adenocarcinoma
RecruitingPhase 2
Perioperative Chemotherapy With Low-Dose Radiotherapy and Tislelizumab for Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Gastric or Gastroesophageal Junction Adenocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Active, not recruitingPhase 2
Perioperative Cadonilimab (AK104) in Locally Advanced MSI-H/dMMR Gastric or Gastroesophageal Junction and Colorectal Adenocarcinoma
MSI-H/dMMR Gastric Carcinoma and Colorectal Cancer
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 2
Candonilimab Combined With Fruquintinib and Paclitaxel Albumin-Bound as Second-Line Treatment for Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma
Stomach Neoplasms
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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing toripalimab FOLFOX in people with Gastroesophageal Adenocarcinoma, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.
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 9 inclusion and 23 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 Aug 2023. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
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?
DLT (time frame: through study completion,an average of 1.5 years). 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 Aug 2023.