Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion
December 12, 2024 updated by: Tianjin Medical University Second Hospital
A Pan-Cancer Basket, Real World, Open-label, Multicenter Study on Molecular Matching Therapy Guided by Molecular Tumor Boards (MTB) for Pan Solid Tumor Patients With Standard Treatment Exhaustion
The main purpose of this study is to explore the feasibility of selecting treatment plans based on genomic variations guided by MTB in patients with advanced refractory solid tumors.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
- Drug: Target Gene
- Drug: Olaparib tablet
- Drug: Temozolomide capsule
- Drug: Anlotinib
- Drug: Trametinib tablet
- Drug: Dabrafenib
- Drug: Vebreltinib Enteric Capsules
- Drug: Alpelisib Pill
- Drug: Sacituzumab Govitecan-Hziy 180 MG
- Drug: Lenvatinib Capsules
- Drug: Pazopanib Pill
- Drug: Palbociclib Pill
- Drug: Chidamide
- Drug: PD-1/PD-L1/PD-1&CTLA4 inhibitor
Detailed Description
Using comprehensive genome sequencing to analyze recurrent and metastatic solid tumors that have failed previous conventional treatments, and matching possible targeted therapy drugs to screen for potential effective treatment drugs until tumor disease progression, and then continuing to monitor tumor resistance mutation signals and provide matching therapy, can help improve the clinical outcomes of patients with advanced refractory tumors, and is also an important direction for personalized and precise treatment of tumors in the future.
Therefore, the investigators designed this study to explore the feasibility, effectiveness, and safety of targeted therapy based on tumor molecular feature matching for advanced solid tumor patients who have failed previous treatments.
All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including clinical efficacy ,clinical safety and exploratory endpoints such as biomarkers for drug response, change in the tumor microenvironment.
The core concepts of the clinical research interventional initiated include: target priority principle, combination therapy principle, individualized dose adjustment method for combination therapy, and Bayesian adaptive trial design.
For some clinical studies, to meet the primary objective, at least 35% of participants had to achieve a PFS2(Progression-Free Survival 2)/PFS1(Progression-Free Survival 1) ≥ 1.3 in a sample population of 25 evaluable patients.
Sample size was calculated using an exact single-stage design for phase II studies with a one-sided type I error of 5% and a power of 90% under the assumption that PFS2/PFS1≥ 1.3 in ≤10% of patients would be clinically irrelevant, while a success rate ≥ 35% would merit further investigation.
Study Type
Interventional
Enrollment (Estimated)
300
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Haitao Wang, Ph.D
- Phone Number: +86-022-88326385
- Email: peterrock2000@126.com
Study Contact Backup
- Name: Jinhuan Wang, Ph.D
- Phone Number: +86-022-88326610
- Email: wjhhappy2008@163.com
Study Locations
-
-
Tianjin
-
Tianjin, Tianjin, China, 300211
- Recruiting
- Tianjin Medical Unversity Second Hospital
-
Sub-Investigator:
- Lili Wang
-
Sub-Investigator:
- Dingkun Hou
-
Principal Investigator:
- Haitao Wang
-
Sub-Investigator:
- Jinhuan Wang
-
Contact:
- Haitao Wang
- Phone Number: +86-02288326610
- Email: peterrock2000@126.com
-
Contact:
- Lili Wang
- Phone Number: +86-13516108466
- Email: wangliliaigang@163.com
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Recurrent or metastatic malignant solid tumors diagnosed by histology or cytology;
- ECOG score 0-4 (3-4 points only for patients with tumor burden);
- Those who fail or cannot tolerate standard treatment, or those who refuse standard treatment;
- At least one measurable lesion that meets the RECIST 1.1 standard;
- Expected survival period ≥ 3 months;
- Age ≥ 18 years old;
- Tumor tissue blocks with sufficient formalin fixed paraffin embedding (FFPE), or chest or ascites with cancer cells detected during treatment (not less than 200ml), or excised metastatic lymph nodes, or peripheral blood (approximately 5m1) can be used for genetic testing;
- Understand and voluntarily participate in this study, and sign the informed consent form.
Exclusion Criteria:
- Patients who have actively undergone or are currently participating in clinical trials for treatment;
- Serious or uncontrolled medical diseases (i.e. uncontrolled diabetes, chronic kidney disease, chronic lung disease or uncontrolled active infection, mental diseases/social conditions that limit the compliance with the research requirements) that the researchers think will confuse the research treatment response analysis;
- Pregnant or lactating patients, or any patients with fertility, have not taken appropriate pregnancy prevention measures.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: Monotherapy
In the OncoKB(Precision Oncology Knowledge Base) database, the gene alteration has a variant of clinical evidence in this tumor or other tumor types and is considered to be an interventional variant.
Cohort-1may include different observation subgroups（dMMR/MSI-H,TMB-H,NTRK fusion,RET-fusion,BRAF(p.V600E),KRAS(p.G12C),HER2(IHC,3+)）.
For example, substudy-1: monotherapy/combination therapy for patients with A1-relative.
Substudy-x: monotherapy/combination therapy for patients with Ax-relative.
|
Granting CFDA or FDA approved drugs(off-label approved drugs) based on specific molecular characteristics.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
|
Experimental: Combination therapy-cohort1
The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration).
|
Granting CFDA or FDA approved drugs(off-label approved drugs) based on specific molecular characteristics.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: The recommended dosage is 200mg, twice a day, equivalent to a total daily dose of 400mg.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided(from the I-PREDICT study).
Administration method and dosage: 75mg/m2, orally administered for 7 consecutive days, with a treatment cycle of every 21 days.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: Take orally once a day before breakfast.
Take the medication continuously for 2 weeks and stop taking it for 1 week, that is, 3 weeks (21 days) is one course of treatment.
Until disease progression or intolerable toxic side effects occur.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: The recommended dose is 2 mg, taken orally once a day with an interval of approximately 24 hours.
The dose should be taken at least 1 hour before meals or 2 hours after meals.
Do not take any missed doses of trametinib within 12 hours of taking the next dose.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: Take 150mg orally twice a day, with an interval of about 12 hours.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
When this product is used in combination with trametinib, it should be taken once a day at the same time, along with this product administered in the morning or evening.The dosage for combined use will be adaptively adjusted by the researcher.
Usage and dosage: The recommended starting dose is 200 mg/time, taken orally twice a day (once in the morning and once in the evening), until disease progression or intolerable toxicity occurs.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: The recommended dosage is 300mg (two 150mg film tablets), taken once a day with food; Continue treatment until the disease worsens or unacceptable toxicity occurs.Administration method: Patients should take aspirin at approximately the same time every day and swallow the entire aspirin tablet (the tablet should not be chewed, crushed, or separated before swallowing).The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: The recommended dosage is 10 mg/kg, administered intravenously every 21 days as a treatment cycle on the 1st and 8th days, and continued until disease progression or unacceptable toxicity occurs.
The dosage of this product should not exceed 10 mg/kg.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: For patients weighing less than 60kg, the recommended daily dose of lenvatinib is 8mg once a day; For patients weighing ≥ 60kg, the recommended daily dose of lenvatinib is 12mg once daily.
Lunvatinib should be taken at a fixed time every day, on an empty stomach or with food.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: In the safety introduction section, the initial dose of pazopanib is 400mg, and in the dose escalation queue, the dose of pazopanib is 600mg.The dosage for combined use will be adaptively adjusted by the researcher. Administration method: Oral treatment once a day, with a cycle of 28 days.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations. Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians. Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: 100mg, orally administered once daily for 21 consecutive days, followed by a 7-day discontinuation; Every 28 days is a treatment cycle.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: It is recommended to take 30mg (6 tablets) each time, twice a week, with an interval of no less than 3 days between each dose (such as Monday and Thursday, Tuesday and Friday, Wednesday and Saturday, etc.).
It should be taken 30 minutes after breakfast.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Refer to the respective instructions for use, and the dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
|
Experimental: Combination therapy-cohort2
The characteristics of enrolled patients are primary or secondary drug resistance during treatment.
|
Granting CFDA or FDA approved drugs(off-label approved drugs) based on specific molecular characteristics.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: The recommended dosage is 200mg, twice a day, equivalent to a total daily dose of 400mg.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided(from the I-PREDICT study).
Administration method and dosage: 75mg/m2, orally administered for 7 consecutive days, with a treatment cycle of every 21 days.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: Take orally once a day before breakfast.
Take the medication continuously for 2 weeks and stop taking it for 1 week, that is, 3 weeks (21 days) is one course of treatment.
Until disease progression or intolerable toxic side effects occur.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: The recommended dose is 2 mg, taken orally once a day with an interval of approximately 24 hours.
The dose should be taken at least 1 hour before meals or 2 hours after meals.
Do not take any missed doses of trametinib within 12 hours of taking the next dose.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: Take 150mg orally twice a day, with an interval of about 12 hours.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
When this product is used in combination with trametinib, it should be taken once a day at the same time, along with this product administered in the morning or evening.The dosage for combined use will be adaptively adjusted by the researcher.
Usage and dosage: The recommended starting dose is 200 mg/time, taken orally twice a day (once in the morning and once in the evening), until disease progression or intolerable toxicity occurs.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: The recommended dosage is 300mg (two 150mg film tablets), taken once a day with food; Continue treatment until the disease worsens or unacceptable toxicity occurs.Administration method: Patients should take aspirin at approximately the same time every day and swallow the entire aspirin tablet (the tablet should not be chewed, crushed, or separated before swallowing).The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: The recommended dosage is 10 mg/kg, administered intravenously every 21 days as a treatment cycle on the 1st and 8th days, and continued until disease progression or unacceptable toxicity occurs.
The dosage of this product should not exceed 10 mg/kg.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: For patients weighing less than 60kg, the recommended daily dose of lenvatinib is 8mg once a day; For patients weighing ≥ 60kg, the recommended daily dose of lenvatinib is 12mg once daily.
Lunvatinib should be taken at a fixed time every day, on an empty stomach or with food.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: In the safety introduction section, the initial dose of pazopanib is 400mg, and in the dose escalation queue, the dose of pazopanib is 600mg.The dosage for combined use will be adaptively adjusted by the researcher. Administration method: Oral treatment once a day, with a cycle of 28 days.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations. Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians. Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: 100mg, orally administered once daily for 21 consecutive days, followed by a 7-day discontinuation; Every 28 days is a treatment cycle.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: It is recommended to take 30mg (6 tablets) each time, twice a week, with an interval of no less than 3 days between each dose (such as Monday and Thursday, Tuesday and Friday, Wednesday and Saturday, etc.).
It should be taken 30 minutes after breakfast.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Refer to the respective instructions for use, and the dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
|
Experimental: Olaparib+Anlotinib/Temozolomide
The gene TP53 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.
|
Usage and dosage: The recommended dosage is 200mg, twice a day, equivalent to a total daily dose of 400mg.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided(from the I-PREDICT study).
Administration method and dosage: 75mg/m2, orally administered for 7 consecutive days, with a treatment cycle of every 21 days.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: Take orally once a day before breakfast.
Take the medication continuously for 2 weeks and stop taking it for 1 week, that is, 3 weeks (21 days) is one course of treatment.
Until disease progression or intolerable toxic side effects occur.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
|
Experimental: Trametinib±Vebreltinib
The gene MAP2K1 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.
|
Usage, dosage, and administration method: The recommended dose is 2 mg, taken orally once a day with an interval of approximately 24 hours.
The dose should be taken at least 1 hour before meals or 2 hours after meals.
Do not take any missed doses of trametinib within 12 hours of taking the next dose.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: Take 150mg orally twice a day, with an interval of about 12 hours.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
When this product is used in combination with trametinib, it should be taken once a day at the same time, along with this product administered in the morning or evening.The dosage for combined use will be adaptively adjusted by the researcher.
|
|
Experimental: Alpelisib
The PMA(PI3K/mTOR/AKT ) pathway active alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.This subgroup is not included in breast cancer patients.
|
Usage and dosage: The recommended dosage is 300mg (two 150mg film tablets), taken once a day with food; Continue treatment until the disease worsens or unacceptable toxicity occurs.Administration method: Patients should take aspirin at approximately the same time every day and swallow the entire aspirin tablet (the tablet should not be chewed, crushed, or separated before swallowing).The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
|
Experimental: Palbociclib+Pazopanib
The gene alteration(Chromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19)) that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.
|
Usage and dosage: In the safety introduction section, the initial dose of pazopanib is 400mg, and in the dose escalation queue, the dose of pazopanib is 600mg.The dosage for combined use will be adaptively adjusted by the researcher. Administration method: Oral treatment once a day, with a cycle of 28 days.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations. Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians. Combinations of drugs with overlapping toxicities were avoided.
Usage, dosage, and administration method: 100mg, orally administered once daily for 21 consecutive days, followed by a 7-day discontinuation; Every 28 days is a treatment cycle.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
|
Experimental: Vebreltinib
MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping/MET-amplification.
|
Usage and dosage: The recommended starting dose is 200 mg/time, taken orally twice a day (once in the morning and once in the evening), until disease progression or intolerable toxicity occurs.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
|
Experimental: Combination therapy group based on PD-1/L1 immune checkpoint inhibitors
MTB combined with clinical practice and literature reports can not match the gene alteration of targeted therapy, which is considered as an irreversible gene alteration.This subgroup may use functional models (including but not limited to PDX(Patient-Derived Tumor Xenograft Model), organoids, etc.) for intervention therapy.
|
Granting CFDA or FDA approved drugs(off-label approved drugs) based on specific molecular characteristics.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: For patients weighing less than 60kg, the recommended daily dose of lenvatinib is 8mg once a day; For patients weighing ≥ 60kg, the recommended daily dose of lenvatinib is 12mg once daily.
Lunvatinib should be taken at a fixed time every day, on an empty stomach or with food.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Usage and dosage: It is recommended to take 30mg (6 tablets) each time, twice a week, with an interval of no less than 3 days between each dose (such as Monday and Thursday, Tuesday and Friday, Wednesday and Saturday, etc.).
It should be taken 30 minutes after breakfast.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
Refer to the respective instructions for use, and the dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations.
Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians.
Combinations of drugs with overlapping toxicities were avoided.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
PFS2/PFS1(Progression Free Survival 2/Progression Free Survival 1)
Time Frame: 24 months
|
The time to progression-free survival during the substudy (PFS2) exceeds the documented time to disease progression-free survival during the last treatment prior to substudy entry (PFS1) by at least 35% (ie, PFS2/PFS1≥1.3)
or, if PFS1 is not evaluable, time to progressive disease exceeds 6 months.
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
OS(Overall Survival)
Time Frame: 24 months
|
Evaluation of overall survival (OS) defined as the time between inclusion and death, whatever the cause is.
Alive patients will be censored at their last known contact date.
|
24 months
|
|
ORR(Objective Response Rate)
Time Frame: 24 months
|
Evaluation of the best objective response rate (ORR) for each treatment according to RECIST 1.1.
The best ORR is the best response reached during treatment according to RECIST 1.1 criteria.
|
24 months
|
|
Number of treatment related adverse events with grade 3 or greater severity by CTCAE 5.0
Time Frame: 24 months
|
Treatment related adverse events with grade 3 or greater severity by CTCAE 5.0.
|
24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Haitao Wang, Ph.D, Tianjin Medical University Second Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 1, 2024
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
May 1, 2027
Study Registration Dates
First Submitted
December 8, 2024
First Submitted That Met QC Criteria
December 12, 2024
First Posted (Actual)
March 25, 2025
Study Record Updates
Last Update Posted (Actual)
March 25, 2025
Last Update Submitted That Met QC Criteria
December 12, 2024
Last Verified
December 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Antineoplastic Agents, Immunological
- Poly(ADP-ribose) Polymerase Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protein Kinase Inhibitors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Immunoconjugates
- Temozolomide
- Immune Checkpoint Inhibitors
- Sacituzumab govitecan
- Trametinib
- Dabrafenib
- Lenvatinib
- Olaparib
- Palbociclib
Other Study ID Numbers
- MyCustom-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.