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AdenocarcinomaPhase 2Miracle-GNCT06121700

Radiotherapy + Chemoimmunotherapy Followed by Surgery in Patients With Limited Metastatic Gastric or GEJ Cancer

A Phase 2 study testing Radiotherapy targeted to the primary lesion, Radiotherapy targeted to the metastatic lesions and Anti-PD-1 monoclonal antibody in people with Adenocarcinoma and Stomach Neoplasm, run by Fudan University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this clinical trial is to evaluate the efficacy and safety of radiotherapy combined with chemotherapy and anti-PD-1 immunotherapy followed by surgery for the primary and metastatic lesions in patients with limited metastatic gastric or gastroesophageal junction adenocarcinoma. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Radiotherapy targeted to the primary lesion, Radiotherapy targeted to the metastatic lesions and Anti-PD-1 monoclonal antibody
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteChina
Study dates
1 Jan 2023to 31 Dec 2027
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histopathologically confirmed adenocarcinoma of stomach (G) or gastroesophageal junction (GEJ) (excluding Siewert type I).
  • Limited metastatic status of disease.
  • At least one evaluable lesion in CT/MRI according to RESIST 1.1 is required.
  • The status of HER2 is clear.
  • pMMR/MSS confirmed by immunohistochemistry or gene test.
  • Male or female. Patient age ≥ 18 years and ≤ 75 years.
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  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
  • Physical state or organ function can tolerate the planned treatment of the study protocol, including systematic chemotherapy, immunotherapy with anti-PD-1 monoclonal antibody (mAb), primary lesion radiotherapy, metastatic lesion radiotherapy, and surgical resection of primary and/or metastatic lesions.
  • No previous surgery or antitumor therapies, including chemotherapy, radiotherapy, or immunotherapy, were administered.
  • Adequate hematological function: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count ≥ 100×109/L; hemoglobin level ≥ 90 g/L.
  • Adequate hepatic function: total bilirubin ≤ 1.5×upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver metastases, or < 5 × ULN in case of liver metastases; ALP ≤ 2.5×ULN; ALB ≥ 30 g/L.
  • Adequate renal function: serum creatinine ≤ 1.5×ULN; creatinine clearance rate ≥ 60 ml/min.
  • Adequate coagulation function: INR/PT ≤ 1.5×ULN; APTT ≤ 1.5×ULN.
  • TSH is within the normal range; if TSH is out of the normal range, FT3 and FT4 should be investigated. If the test results of FT3/FT4 cannot be obtained, T3 and T4 can be accepted. 13. If the level of T3/T4 is normal, the patients can be selected.
  • Urine test: urine protein<2+; if the urine protein≥2+, the 24-hour urine protein quantification must be≤1g.
  • There is no serious concomitant disease, and the patient's life expectancy is more than 6 months.
  • Patients agree to sign written informed consent before recruitment.
  • Patients are willing and able to follow the protocol during the study, including receiving treatment and scheduled follow-up and examination.
  • Patients are willing to provide samples of blood and tissue.
  • Female patients should not be pregnant or breast feeding.
  • Female patients agree to take contraceptive measures during treatment and within 120 days after the last dose of anti-PD-1 mAb or 180 days after the last use of chemotherapy or radiotherapy.
  • Definition of the limited metastatic disease:
  • Retroperitoneal lymph node metastases (RPLM) only or at maximum one organ involved with or without RPLM.
  • There is no peritoneal seeding on diagnostic laparoscopy (P0).
  • The definition of RPLM includes but is not limited to para-aortal, intra-aorto-caval, parapancreatic or mesenteric lymph nodes. If the duodenum is invaded, retropancreatic nodes are not regarded as M1.
  • The definition of single organ metastasis in the study is as follows: a) Liver: maximum of 5 metastatic lesions that are potentially resectable and the metastases should be limited to one lobe and not involve important blood vessels or bile ducts. b) Lung: unilateral involvement, potentially resectable. c) Ovary: uni- or bilateral Krukenberg tumors in the absence of macroscopic peritoneal carcinomatosis. d) Adrenal gland: uni- or bilateral metastases. e) Extra-abdominal lymph node metastases, such as supraclavicular or cervical lymph node involvement. f) Bone: localized bone involvement (defined as being within one radiation field).
  • Other metastatic disease locations are considered, limited by the investigator and confirmed by the multidisciplinary team (MDT).

Who cannot join

  • Patients who have previously received surgery, chemotherapy, radiotherapy or immunotherapy for gastric cancer.
  • Patients have a history of cancer in the five years before enrollment except for squamous or basal cell carcinoma of the skin that was effectively treated and superficial bladder cancer, cervical carcinoma in situ and breast cancer in situ that was treated by operation.
  • Pregnant or lactating females or females planning to become pregnant or lactating. Women of childbearing age with a positive pregnancy test or without a pregnancy test in the baseline period. Menopausal women must have stopped menstruating for at least 12 months before being considered to have no chance of pregnancy.
  • Patients who had sexual activity (with the possibility of childbirth) and were unwilling to use contraception during the study period.
  • Patients with a history of allergies to any drugs that may be used in this study, including chemotherapy drugs.
  • History of allogeneic stem cell transplantation or organ transplantation.
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  • Vaccinated with live vaccine within 28 days before recruitment.
  • Immunotherapy (interleukin, interferon, thymine) or other experimental treatment was given 28 days before enrollment.
  • History of anti-PD-1, PD-L1, PD-L2 or any other specific T-cell costimulation or checkpoint pathway targeted therapy.
  • History of using steroids (dose > 10 mg/d prednisone) or other systemic immunosuppressive therapy within 14 days before recruitment, except for patients treated with the following regimen: steroids used for hormone replacement (dose > 10 mg/d prednisone); local application of steroids with little systemic absorption; short-term (≤ 7 days) use of steroids to prevent allergy or vomiting.
  • Patients with weight loss of more than 20% within 2 months before recruitment.
  • Uncontrolled systemic diseases, including diabetes, hypertension, etc.
  • Uncontrollable pleural effusion, pericardial effusion, or ascites occurred within two weeks before recruitment.
  • Failure of important organs (heart, lung, liver, kidney, etc.).
  • Moderate or severe renal injury [creatinine clearance ≤ 50 ml/min (according to Cockcroft \& Gault equation)], or SCR > ULN.
  • Dipyrimidine dehydrogenase (DPD) deficiency.
  • Patients with central nervous system (CNS) disorders or tumors, including brain metastases, peripheral nervous system disorders or psychiatric diseases.
  • Cerebrovascular accidents occurred within 6 months before recruitment.
  • Patients with peripheral neuropathy of NCI-CTCAE grade 1, except for those with disappearance of the deep tendon reflex.
  • Patients with a known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and hypertension, congestive heart failure, cardiac infarction or cardiac insufficiency within 6 months prior to study recruitment.
  • Pulmonary embolism occurred within 28 days before enrollment.
  • Patients who had the following history of pulmonary diseases: interstitial lung disease, noninfectious pneumonia, pulmonary fibrosis, or acute lung disease.
  • Patients with gastrointestinal bleeding or a high risk of bleeding within the first 2 weeks of enrollment.
  • Patients who experienced gastrointestinal perforation or fistula within 6 months prior to enrollment.
  • Upper gastrointestinal obstruction, dysfunction or malabsorption syndrome may affect the absorption of oral chemotherapy drugs.
  • Patients who cannot swallow or take medication orally.
  • Patients with a history of active autoimmune disease or refractory autoimmune disease.
  • Severe chronic or active infections requiring systemic antibiotics, antifungal or antiviral therapy, including tuberculosis and AIDS.
  • Known history of human immunodeficiency virus (HIV) infection.
  • Patients with untreated chronic hepatitis B or HBV-DNA exceeding 500 IU/ml or HCV-RNA positive.
  • Alcohol/drug abuse and medical, psychological or social conditions may interfere with patients' participation in the study or have an impact on the evaluation of the study results.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Menglong Zhou, MD contact

86-18121299608

mrzhouml@163.com

China1 site, 1 recruiting

  • Fudan University Shanghai Cancer Center

    Shanghai

    Menglong Zhou, MD, 86-18121299608, mrzhouml@163.com

    Dazhi Xu, MD

    Recruiting

Other trials in China

About this study

Official title: Radiotherapy, Chemotherapy and Anti-PD-1 Immunotherapy Followed by Surgical Resection in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: A Prospective, Single Arm, Phase II Trial

The goal of this clinical trial is to evaluate the efficacy and safety of radiotherapy combined with chemotherapy and anti-PD-1 immunotherapy followed by surgery for the primary and metastatic lesions in patients with limited metastatic gastric or gastroesophageal junction adenocarcinoma. The main questions it aims to answer are: 1) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies will improve the survival of this group of patients. 2) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies can be performed safely in this group of patients.

Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.

Being tested
Radiotherapy targeted to the primary lesion, Radiotherapy targeted to the metastatic lesions, Anti-PD-1 monoclonal antibody, Trastuzumab, Chemotherapy
Keywords
gastric cancer, GEJ Cancer, oligometastasis, limited metastatic, hypofractionated radiotherapy, immunotherapy, gastrectomy, metastasectomy
Medical subject headings
Adenocarcinoma, Stomach Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Radiotherapy targeted to the primary lesionRadiation

    5 to 7 fractions of short course hypofractionated radiotherapy (HFRT) targeted to the primary lesion.

  • Radiotherapy targeted to the metastatic lesionsRadiation

    Hypofractionated radiotherapy (HFRT) or stereotactic body radiotherapy (SBRT) targeted to metastatic lesions. The target dose will be adjusted based on the lesion's site and diameter and organs at risk, with high-dose irradiation of 4-8 fractions. All metastatic lesions should be irradiated as much as possible, and partial lesion irradiation should be allowed when technically impractical.

  • Anti-PD-1 monoclonal antibodyBiological

    The anti-PD-1 mAb is used on day 1 along with each cycle of chemotherapy. There are no restrictions on the choice of anti-PD-1 mAb. Patients can choose commonly used accessible monoclonal antibodies based on their personal preferences and financial status.

    The commonly used anti-PD-1 mAb usages are as follows: Nivolumab/Toripalimab 240mg solution intravenously once daily, Q2W. OR Nivolumab/Toripalimab 360mg solution intravenously once daily, Q3W; OR Pembrolizumab/Tislelizumab/Sintilimab/Camrelizumab, 200mg solution intravenously once daily, Q3W.

  • TrastuzumabBiological

    Also called Herceptin®

    For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. The 3-weekly schedule of trastuzumab starts with a loading dose of trastuzumab of 8 mg/kg, followed by 6 mg/kg trastuzumab every 21 days.

  • ChemotherapyDrug

    The investigator's choice of chemotherapy regimens included SOX, XELOX or FOLFOX. Their usages are as follows:

    SOX: S-1 twice a day, days 1-14, the dose of S-1 is accorded to body-surface area (BSA): patients with a BSA of less than 1.25 m2 receive 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 receive 100 mg daily; and those with a BSA of 1.5 m2 or more receive 120 mg daily; and oxaliplatin 130 mg/m2, day 1, every 3 weeks; XELOX: Capecitabine 1000 mg/m2 twice a day, days 1-14 and oxaliplatin 130 mg/m2, day 1, every 3 weeks; FOLFOX: Leucovorin 400 mg/m2, day 1, fluorouracil 400 mg/m2, day 1 and 1200 mg/m2, days 1-2, and oxaliplatin 85 mg/m2, day 1, every 2 weeks.

  • R0 total/subtotal gastrectomy with D2 lymphadenectomyProcedure or surgery

    For patients with a good response to preoperative treatment, surgical resection of primary and metastatic lesions is recommended. For primary lesions, gastrectomy with standard D2 lymphadenectomy is commonly used. The type of gastrectomy performed depends on the location and extent of the primary lesion. For GEJ or upper-third tumors, a 3 cm esophageal margin is recommended, and a total gastrectomy or esophagogastrectomy is performed. For middle-third tumors, the gastric margin is recommended to be more than 5 cm, and total gastrectomy is performed. For lower-third tumors, a 2 cm duodenal margin is recommended, and subtotal or total gastrectomy is performed. Billroth I or Roux-en-Y gastrojejunostomy is performed for distal gastrectomy patients. Roux-en-Y esophagojejunostomy is performed for patients receiving total gastrectomy.

  • MetastasectomyProcedure or surgery

    For patients with a good response to preoperative treatment, surgical resection of primary and metastatic lesions is recommended. For metastatic lesions, the surgical procedure and resection range are determined by the surgeon.

  • Local ablative therapiesProcedure or surgery

    Local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) achieve high rates of complete tumor eradication of small metastases, and can be seen as alternatives if a widely invasive surgical approach is required or patient is inoperable.

Study groups in NCT06121700
Study groupRoleWhat they receive
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical ResectionExperimentalParticipants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Receives: Radiation: Radiotherapy targeted to the primary lesion; Radiation: Radiotherapy targeted to the metastatic lesions; Biological: Anti-PD-1 monoclonal antibody; Biological: Trastuzumab; Drug: Chemotherapy; Procedure: R0 total/subtotal gastrectomy with D2 lymphadenectomy; Procedure: Metastasectomy; Procedure: Local ablative therapies

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    The time from enrollment to death due to any reason.

    Measured: From the time of enrollment, assessed up to 5 years follow-up.

Secondary outcomes (6)

  1. No evidence of disease (NED) rate

    Rate of no evidence of disease for one year

    Measured: Assessed 1 year after treatment

  2. Objective response rate (ORR)

    Proportion of patients with complete response (CR) or partial response (PR) to preoperative multimodal therapy. ORR will be evaluated using RESIST1.1 by CT/MRI of the chest, abdomen, and pelvis.

    Measured: From the time of enrollment, assessed up to 5 years follow-up.

  3. Progression-free survival (PFS)

    The time from enrollment to disease progression or death from any cause.

    Measured: From the time of enrollment, assessed up to 5 years follow-up.

  4. Toxicities

    Number of participants with treatment-related adverse events (TrAEs) reported between the first dose and 28 days after the last dose of study therapy as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

    Measured: From the time of enrollment, assessed up to 28 days after the last dose of study therapy

  5. Surgical morbidity

    Surgery-related adverse events (SRAEs) refer to complications which happen during or one month after surgery. Severe complications after surgery will be documented and classified by Clavien-Dindo classification, such as abdominal or GI tract bleeding, anastomotic fistula, pancreatic fistula of grade B or above, and incision complications (infection, bleeding, rupture).

    Measured: During or one month after surgery

  6. Surgical mortality

    Death from any cause within 30 days of the date of surgery will be considered a surgical mortality death.

    Measured: During or one month after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2023
  2. Study start1 Jan 2023
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

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
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06121700
Sponsor's protocol ID
FDRT-2022-260-2977
Acronym
Miracle-G
Status last verified
Nov 2023
First submitted
19 Oct 2023
Last updated
8 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, Schmalenberg H, Luley KB, Prasnikar N, Egger M, Probst S, Messmann H, Moehler M, Fischbach W, Hartmann JT, Mayer F, Hoffkes HG, Koenigsmann M, Arnold D, Kraus TW, Grimm K, Berkhoff S, Post S, Jager E, Bechstein W, Ronellenfitsch U, Monig S, Hofheinz RD. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017 Sep 1;3(9):1237-1244. doi: 10.1001/jamaoncol.2017.0515.

    PubMed 28448662

  • Al-Batran SE, Goetze TO, Mueller DW, Vogel A, Winkler M, Lorenzen S, Novotny A, Pauligk C, Homann N, Jungbluth T, Reissfelder C, Caca K, Retter S, Horndasch E, Gumpp J, Bolling C, Fuchs KH, Blau W, Padberg W, Pohl M, Wunsch A, Michl P, Mannes F, Schwarzbach M, Schmalenberg H, Hohaus M, Scholz C, Benckert C, Knorrenschild JR, Kanngiesser V, Zander T, Alakus H, Hofheinz RD, Roedel C, Shah MA, Sasako M, Lorenz D, Izbicki J, Bechstein WO, Lang H, Moenig SP. The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer. 2017 Dec 28;17(1):893. doi: 10.1186/s12885-017-3918-9.

    PubMed 29282088

  • Zhou ML, Xu RN, Tan C, Zhang Z, Wan JF. Advanced gastric cancer achieving major pathologic regression after chemoimmunotherapy combined with hypofractionated radiotherapy: A case report. World J Gastrointest Oncol. 2023 Jun 15;15(6):1096-1104. doi: 10.4251/wjgo.v15.i6.1096.

    PubMed 37389115

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiotherapy targeted to the primary lesion, Radiotherapy targeted to the metastatic lesions and Anti-PD-1 monoclonal antibody in people with Adenocarcinoma and Stomach Neoplasm, 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 27 inclusion and 31 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 8 Nov 2023. 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 Menglong Zhou, MD (86-18121299608, mrzhouml@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: From the time of enrollment, assessed up to 5 years follow-up.). 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 NCT06121700, which also lists 3 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 8 Nov 2023.

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