Study of Precision Treatment for Rare Tumours in China Guided by PDO and NGS
SPRING
A Phase II Clinical Study on Precision Treatment of Rare Tumours in China Guided by Patient-Derived Tumor Organoids (PDO) and Next-Generation Sequencing (NGS)
1 other identifier
interventional
200
0 countries
N/A
Brief Summary
The objective of this Phase II, open-label, multicenter, non-randomised controlled clinical trial is to guide precision treatment for patients with rare tumours based on Patient-Derived Organoids/Next-Generation Sequencing drug screening.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2025
Longer than P75 for phase_2
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 16, 2024
CompletedFirst Posted
Study publicly available on registry
November 18, 2024
CompletedStudy Start
First participant enrolled
January 1, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2029
November 18, 2024
November 1, 2024
3 years
September 16, 2024
November 14, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR)
The percentage of patients with a confirmed investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1.
From enrollment to the end of treatment at 8 weeks
Secondary Outcomes (4)
Disease Control Rate (DCR)
From enrollment to the end of treatment at 8 weeks
Progression free survival (PFS)
From enrollment to the end of treatment at 8 weeks
Overall survival (OS)
From enrollment to the end of treatment at 8 weeks
Duration of response (DOR)
From enrollment to the end of treatment at 8 weeks
Study Arms (4)
Standard treatment Group
NO INTERVENTIONPatients with rare tumours in this group will undergo standard treatment in accordance with the leading domestic and international guidelines (NCCN/ESMO/CSCO/CACA) and clinical trial.
Criteria-Fulfilled ICF Group
EXPERIMENTALIntervention in this group is to perform PDOs culture and drug screening of lesions from patients with rare tumours who failed to standard treatment and fully meet the inclusion and exclusion criteria. The MTB will review the results of the drug screening and NGS, and subsequently determine the personalised chemotherapy, targeted or immunological agents.
Compassionate-Use ICF Group
EXPERIMENTALPatients with rare tumours who failed to standard treatment and do not meet the requisite criteria (e.g. active hepatitis B, underlying disease in the exclusion criteria, symptomatic brain metastases) will provide informed consent and undergo PDOs culture and drug screening. The MTB will review the results of the drug screening and NGS, and subsequently determine the personalised chemotherapy, targeted or immunological agents.
RWS ICF Group
EXPERIMENTALPatients with rare tumours who failed to standard treatment will be included in a real-world study cohort and receive clinically conventional treatment if they do not undergo PDOs culture and NGS testing successfully or are unwilling to base their treatment on the results of PDOs and NGS for various reasons.
Interventions
Albumin-Bound Paclitaxel 260mg/m2,q3w Patients with advanced rare tumours who failed to standard treatment will be administrated with albumin-bound paclitaxel if PDOs show the highest response to this drug under the guidance of MTB.
Epirubicin 90mg/m2,q3w Patients with advanced rare tumours who failed to standard treatment will be administrated with epirubicin if PDOs show the highest response to this drug under the guidance of MTB.
Gemcitabine 1000mg/m2,D1,D8,q3w Patients with advanced rare tumours who failed to standard treatment will be administrated with gemcitabine if PDOs show the highest response to this drug under the guidance of MTB.
Vinorelbine 25-30mg/m2,D1,D8,q3w Patients with advanced rare tumours who failed to standard treatment will be administrated with vinorelbine if PDOs show the highest response to this drug under the guidance of MTB.
Cisplatin 90mg/m2,q3w Patients with advanced rare tumours who failed to standard treatment will be administrated with cisplatin if PDOs show the highest response to this drug under the guidance of MTB.
Irinotecan 125mg/m2,D1,D8,q3w Patients with advanced rare tumours who failed to standard treatment will be administrated with irinotecan if PDOs show the highest response to this drug under the guidance of MTB.
Fluorouracil 600mg/m2,D1-5,q3w Patients with advanced rare tumours who failed to standard treatment will be administrated with fluorouracil if PDOs show the highest response to this drug under the guidance of MTB.
Nivolumab 3mg/kg,q2w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with nivolumab under the guidance of MTB.
Pembrolizumab 200mg,q2w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with pembrolizumab under the guidance of MTB.
Durvalumab 10mg/kg,q3w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with durvalumab under the guidance of MTB.
Atezolizumab 1200mg,q3w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with atezolizumab under the guidance of MTB.
Sintilimab 200mg,q3w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with sintilimab under the guidance of MTB.
Tislelizumab 200mg,q3w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with tislelizumab under the guidance of MTB.
Camrelizumab 200mg,q3w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with camrelizumab under the guidance of MTB.
Toripalimab 240kg,q3w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with toripalimab under the guidance of MTB.
Serplulimab 3mg/kg,q2w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with serplulimab under the guidance of MTB.
Adebrelimab 20mg/kg,q3w Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with adebrelimab under the guidance of MTB.
Envafolimab 150mg,qw Patients with advanced rare tumours who failed to standard treatment carrying no targeted alterations will be administrated with envafolimab under the guidance of MTB.
Osimertinib 80mg,qd Patients with advanced rare tumours who failed to standard treatment carrying EGFR mutations will be administrated with osimertinib under the guidance of MTB.
Alectinib 600mg,bid Patients with advanced rare tumours who failed to standard treatment carrying ALK fusion will be administrated with alectinib under the guidance of MTB.
Vemurafenib 960mg,bid Patients with advanced rare tumours who failed to standard treatment carrying BRAF V600E mutation will be administrated with vemurafenib under the guidance of MTB.
Pamiparib 60mg,bid Patients with advanced rare tumours who failed to standard treatment carrying BRCA1/2 mutation will be administrated with pamiparib under the guidance of MTB.
Pyrotinib 400mg, qd Patients with advanced rare tumours who failed to standard treatment carrying HER-2 mutation or HER-2 over expression/amplification will be administrated with Pyrotinib under the guidance of MTB.
Imatinib 400mg, qd Patients with advanced rare tumours who failed to standard treatment carrying CKIT mutation will be administrated with imatinib under the guidance of MTB.
Palbociclib 125mg, 21/7 dosing schedule Patients with advanced rare tumours who failed to standard treatment following HR(+)/HER-2(-) will be administrated with palbociclib under the guidance of MTB.
Savolitinib 300mg, qd Patients with advanced rare tumours who failed to standard treatment carrying C-MET mutation will be administrated with savolitinib under the guidance of MTB.
Entrectinib 600mg, qd Patients with advanced rare tumours who failed to standard treatment carrying ROS-1 fusion or NTRK fusion will be administrated with entrectinib under the guidance of MTB.
Patients with advanced rare tumours who failed to standard treatment in RWS ICF Group will be administrated with empirical chemotherapy(e.g., "Albumin-Bound Paclitaxel", "Epirubicin", "Gemcitabine", "Vinorelbine", "Cisplatin", "Irinotecan", "Fluorouracil"), immunological(e.g., "Nivolumab", "Pembrolizumab", "Durvalumab", "Atezolizumab", "Sintilimab", "Tislelizumab", "Camrelizumab", "Toripalimab", "Serplulimab","Adebrelimab","Envafolimab") or targeted drugsl(e.g., "Osimertinib", "Alectinib", "Vemurafenib", "Vemurafenib", "Pyrotinib", "Imatinib", "Palbociclib", "Savolitinib", "Entrectinib")treatments.
Eligibility Criteria
You may qualify if:
- Male or female, the age at the time of signing the informed consent is no less than 18 years old;
- Patients with advanced or metastatic rare solid tumor confirmed by histological confirmed;
- ECOG score is 0 or 1;
- Expected survival ≥12 weeks;
- According to Response Evaluation Criteria in Solid Tumor (RECIST 1.1), there is at least one imaging measurable lesions, which has not previously undergone radiotherapy or with obvious disease progress after radiotherapy;
- Surgical specimens of paired tumor tissue and adjacent normal tissue, or fresh biopsy tissue samples or ≥500ml serous cavity effusion with positive pathological cytological examination must be provided. These specimens must be obtained without prior exposure to any other anti-tumor treatment, systemic anti-infection treatment, vaccination, et al. and are intended for organoid culture;
- Must have a primary or metastatic paraffin-embedded tissue (without radiotherapy) other than bone metastatic lesions before enrollment (within 2 years, 15-20 sheets, 4-6μm thick white slices, of which 5 need to be glued and baked ) and peripheral blood samples for NGS gene testing. If NGS results are already available but sufficient paraffin-embedded tissue cannot be provided, investigator are allowed the decision to enroll subjects according to the specific situation;
- In the condition that the primary lesions biopsy specimen has been provided, if the metastatic lesion is able to be biopsied(determined by investigator), it is suggested to keep the specimen for pathological testing and provide fresh tissue specimen;
- After the progression of the subject\'s disease, if conditions permit(determined by investigator), fresh tissue samples shall be obtained from the same biopsy lesions and the metastasis lesions of the previously obtained samples;
- Toxic and side effects caused by previous treatment need to be restored to ≤ Grade 1 or returned to the baseline value (NCI-CTCAE version 5.0, except for hair loss);
- Negative pregnancy test (only applicable for women with childbearing potential). No childbearing potential is defined as being postmenopausal for longer than one year or having undergone surgical sterilization or hysterectomy;
- All patients (male and female) agree to use an effective form of contraceptive measures during the treatment and within 8 weeks after the end of treatment;
- Signed, written informed consent of volunteers that join the group shall follow the trial treatment plan, follow-up plan and cooperate to observe the adverse events and efficacy.
You may not qualify if:
- No patient lesions available for organoid model construction;
- History of interstitial lung disease or radiation pneumonitis of any type;
- Central Nervous System (CNS) metastases with brain metastases-related symptoms, which is not stable in neurology, or need to increase steroid dosage to control CNS disease. (Note: Patients with controlled CNS metastasis are eligible to participate in this study);
- Current uncontrollable third cavity effusion, such as a large amount of pleural effusion，ascites , or pericardial effusion;
- Major surgical operations or incomplete healing of injury within 4 weeks prior to study treatment\'s first administration and chest radiotherapy of \> 30 Gy within 6 months;
- History of receiving other investigational drugs within 14 days or 5 half-lives (whichever is longer) prior to the first administration;
- History of receiving live vaccine within 30 days prior to the first administration. Seasonal influenza vaccines that do not contain live viruses are allowed;
- Current active infection requiring systemic treatment (antibiotics); or any of the following:
- HIV positive or known history of acquired immunodeficiency syndrome;
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is defined as HBsAg positive and the number of HBV DNA copies exceeds the upper limit of normal value, or HCV AB positive;
- Active tuberculosis (with exposure history or positive tuberculosis test; with clinical and / or imaging manifestations);
- Positive antibody of Treponema Pallidum
- Current evidenced uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[still greater than or equal to CTCAE Grade 3 hypertension after drug treatment\]);
- History of myocardial infarction, coronary artery / peripheral artery bypass or cerebrovascular accident within 3 months;
- Diagnosed with a second type of malignant tumor within 5 years before the first diagnosis of a rare solid tumor (excluding completely resected basal cell carcinoma, bladder carcinoma in situ, cervical carcinoma in situ);
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
shunbin wang, Doctor
Peking University Shenzhen Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director of Medical Oncology
Study Record Dates
First Submitted
September 16, 2024
First Posted
November 18, 2024
Study Start
January 1, 2025
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2029
Last Updated
November 18, 2024
Record last verified: 2024-11