Trial Title:
Conversion Therapy of Sintilimab in Combination With Fruquintinib and Chemotherapy Versus Sintilimab and Chemotherpay in Stage IV Gastric Cancer
NCT ID:
NCT06454435
Condition:
Gastric Cancer
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Stomach Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sintilimab + Fruquinitinib + S-1 plus nab-paclitaxel
Description:
Drug: Sintilimab Sintilimab 200mg, D1, IV, Q3W 4-8 cycles Drug: Fruquintinib
Fruquinitinib 4mg/d, QD, PO, D1-D14, Q3W 4-8 cycles Drug: S-1 BSA<1.25 m2, 40mg
twice/day; BSA 1.25-1.5m2, 50mg twice/day; BSA≥1.5 m2, 60mg twice/day, po, D1-D14, Q3W
4-8 cycles Drug: Nab-paclitaxel
- without peritoneal metastases: 260 mg/m2, IV, D1 for 3h, Q3W 4-8 cycles;
- with peritoneal metastases: 80mg/m2 IP, plus 180mg/m2, IV, D1, Q3W 4-8 cycles.
Arm group label:
Sintilimab + Fruquinitinib + S-1 plus nab-paclitaxel
Intervention type:
Drug
Intervention name:
Sintilimab + S-1 plus nab-paclitaxel
Description:
Drug: Sintilimab Sintilimab 200mg, D1, IV, Q3W 4-8 cycles Drug: S-1 BSA<1.25 m2, 40mg
twice/day; BSA 1.25-1.5m2, 50mg twice/day; BSA≥1.5 m2, 60mg twice/day, po, D1-D14, Q3W
4-8 cycles Drug: Nab-paclitaxel
- without peritoneal metastases: 260 mg/m2, IV, D1 for 3h, Q3W 4-8 cycles;
- with peritoneal metastases: 80mg/m2 IP, plus 180mg/m2, IV, D1, Q3W 4-8 cycles.
Arm group label:
Sintilimab + S-1 plus nab-paclitaxel
Summary:
This is a multicenter, randomized, open-label, phase 2 clinical study aiming to evaluate
the feasibility and efficacy of sintilimab (PD-1 inhibitor) in combination of
fruquintinib and chemotherapy (S-1 plus nab-paclitaxel) versus sintilimab and
chemotherapy as conversion therapy in patients with stage IV gastric cancer in China.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically confirmed gastric/gastroesophageal junction adenocarcinoma through
gastroscopy.
- Ages: 18-70 Years (concluding 18 and 70 Years)
- Life expectancy ≥3 months.
- Treatment-naive Stage IV (clinical staging, AJCC 8th) unresectable patients, no
prior antitumor therapy (including radiation, chemotherapy, targeted therapy or
immunotherapy, etc.).
- The Eastern Cooperative Oncology Group Performance status (ECOG PS) of 0-1.
- Preoperative examinations using CT, MRI, PET-CT, etc., indicating only one
unresectable factor OR peritoneal metastasis with another unresectable factor, such
as:
1. N3 lymph node metastasis, mainly referring to group 16 lymph node metastasis.
2. Extensive or bulky lymph nodes (D2)
3. Locally advanced T4b.
4. Hepatic metastases (H1): ≤5 lesions with a total diameter ≤8cm.
5. Peritoneal metastasis (CY1, P1).
6. Ovarian metastasis (Krukenberg tumor).
- Physically fit for major abdominal surgery.
- Adequate organ and marrow function, defined as:
1. Hematological status: Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet
count (PLT) ≥100×10^9/L; Hemoglobin (HGB) ≥9.0 g/dL.
2. Liver function: For patients without liver metastasis, serum total bilirubin
(TBIL) ≤1.5× upper limit of normal (ULN); ALT and AST ≤2.5×ULN. For patients
with liver metastasis: TBIL ≤1.5×ULN; ALT and AST ≤5×ULN.
3. Renal function: Creatinine clearance (Ccr) ≥50 mL/min (calculated using the
Cockcroft/Gault formula).
- Adequate coagulation function, defined as International Normalized Ratio (INR) or
Prothrombin Time (PT) ≤1.5 times ULN.
- Voluntary participation and signed informed consent with expected good compliance
and follow-up.
- Not involved in other clinical trials.
- Willing to provide blood and histological samples.
- No serious conditions affecting anesthesia, or surgery.
- No hematologic disorders affecting postoperative hemoglobin levels.
Exclusion Criteria:
- Has distal metastases other than oligometastases as defined in the inclusion
criteria, such as pulmonary metastases, brain metastases, bone metastases, etc.
- HER-2 positive patients or willing to receive Trastuzumab.
- Endoscopic signs of active bleeding from the lesion.
- Patients with moderate/large volume of ascites.
- Near-obstruction at the cardia or pylorus affecting feeding and gastric emptying or
difficulty swallowing tablets.
- Concurrently suffering from other serious illnesses that are difficult to control
(Severe uncontrolled recurrent infections, atrial fibrillation, angina pectoris,
cardiac insufficiency, ejection fraction measurement under 50%, uncontrolled
hypertension, renal insufficiency, symptomatic peripheral neuropathy, and NCI
classification >II)
- Has already on other medications prior to enrollment or could not be assured of
compliance after enrollment.
- Allergy to any drugs in the regimen.
- Women who are pregnant or breastfeeding and have childbearing potential but are not
taking adequate contraceptive measures.
- Organ transplant recipients requiring immunosuppression.
- Patients without decision-making capacity or with psychiatric disorders.
- Systemic treatment with Chinese herbal anti-tumor or immunomodulatory drugs
(including thymosin, interferons, interleukins) within 2 weeks before the first
dose.
- Use of immunosuppressive drugs within 4 weeks before the first study treatment,
excluding local steroids or physiological doses of systemic steroids.
- Has received a live or live-attenuated vaccine within 30 days prior to the first
dose of study treatment.
- Has a diagnosis of autoimmune disease within the previous 2 years (Patients with
vitiligo, psoriasis, alopecia areata, or Graves' disease who do not require systemic
therapy within the last 2 years, hypothyroidism requiring only thyroid hormone
replacement therapy, and type I diabetes mellitus requiring only insulin replacement
therapy are eligible for enrollment).
- Known history of primary immunodeficiency.
- Known to have active tuberculosis.
- Has history of human immunodeficiency virus (HIV) infection (i.e., HIV antibody .
positive); untreated acute or chronic active hepatitis B or hepatitis C infection.
Patients receiving antiretroviral therapy are eligible for enrollment on an
individual basis as determined by the physician with monitoring of viral copy
number.
- Urinalysis indicating urine protein ≥2+ and 24-hour urine protein quantification
>1.0g.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital
Address:
City:
Tianjin
Zip:
210000
Country:
China
Contact:
Last name:
Han Liang, MD
Phone:
18622221082
Email:
tjlianghan@126.com
Start date:
June 2024
Completion date:
June 2027
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06454435
