Solid Tumor, Precision Medicine
Conditions
Brief summary
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.
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.
Interventions
DRUGOlaparib tablet
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.
DRUGAnlotinib
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.
DRUGTarget Gene
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, 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.
DRUGDabrafenib
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.
DRUGAlpelisib Pill
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.
DRUGSacituzumab Govitecan-Hziy 180 MG
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.
DRUGPazopanib Pill
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.
DRUGPalbociclib Pill
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.
DRUGChidamide
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.
DRUGPD-1/PD-L1/PD-1&CTLA4 inhibitor
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.
Sponsors
Tianjin Medical University Second Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Recurrent or metastatic malignant solid tumors diagnosed by histology or cytology; 2. ECOG score 0-4 (3-4 points only for patients with tumor burden); 3. Those who fail or cannot tolerate standard treatment, or those who refuse standard treatment; 4. At least one measurable lesion that meets the RECIST 1.1 standard; 5. Expected survival period ≥ 3 months; 6. Age ≥ 18 years old; 7. 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; 8. Understand and voluntarily participate in this study, and sign the informed consent form.
Exclusion criteria
1. Patients who have actively undergone or are currently participating in clinical trials for treatment; 2. 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; 3. Pregnant or lactating patients, or any patients with fertility, have not taken appropriate pregnancy prevention measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS2/PFS1(Progression Free Survival 2/Progression Free Survival 1) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS(Overall Survival) | 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. |
| ORR(Objective Response Rate) | 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. |
| Number of treatment related adverse events with grade 3 or greater severity by CTCAE 5.0 | 24 months | Treatment related adverse events with grade 3 or greater severity by CTCAE 5.0. |
Countries
China
Contacts
Primary ContactHaitao Wang, Ph.D
Backup ContactJinhuan Wang, Ph.D
Outcome results
None listed