Targeted Agent and Profiling Utilization Registry (TAPUR) Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 4,200
- 试验地点
- 284
- 主要终点
- Objective Response Rate defined as % of participants in a cohort with complete or partial response or with stable disease according to standard response criteria
研究概览
简要总结
The purpose of the study is to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target or to predict sensitivity to a drug.
NOTE: Due to character limits, the arms section does NOT include all TAPUR Study relevant biomarkers. For additional information, contact TAPUR@asco.org, or if a patient, your nearest participating TAPUR site (see participating centers).
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Results in publication or poster presentation format are posted as they become available for individual cohorts at www.tapur.org/news. The results may be accessed at any time. All results will be made available on clinicaltrials.gov at the end of the study. Indexing of available results on PubMed is in progress.
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详细描述
The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a non-randomized clinical trial that aims to describe the safety and efficacy of commercially available, targeted anticancer drugs prescribed for treatment of patients with advanced cancer that has a potentially actionable genomic variant. TAPUR will study Food and Drug Administration (FDA)-approved targeted therapies that are contributed by collaborating pharmaceutical companies, catalogue the choice of molecular profiling test by clinical oncologists and develop hypotheses for additional clinical trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •12 years of age or older (*Restrictions apply. Not all therapies are available for patients <18)
- •Histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer treatment or for whom, in the opinion of the treating physician, no such treatment is available or indicated (except under the circumstance in which the TAPUR arm is designed to provide additional evidence to support an existing FDA indication).
- •Performance status 0-2 (Per Eastern Cooperative Oncology Group (ECOG) criteria)
- •Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/
排除标准
- •specified in the protocol appendix for each agent will take precedence for this and all inclusion criteria:
- •Absolute neutrophil count ≥ 1500 µl
- •Hemoglobin ≥ 9.0 g/dl
- •Platelets ≥ 75,000/µl
- •Total bilirubin < 2.0 mg/ dl, except in patients with Gilbert's Syndrome
- •Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) < 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with known hepatic metastases)
- •Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2
- •Patients must have disease that can be objectively measured by physical, laboratory or radiographic exam (per RECIST v1.1 for solid tumor, Lugano criteria for non-Hodgkin lymphoma or International Myeloma Working Group criteria for multiple myeloma).
- •Results must be available from a genomic test or immunohistochemistry (IHC) test for protein expression performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited or New York State accredited (for labs offering services to residents of NY) laboratory. Labs that have registered the test with the NIH Genetic Testing Registry or that provide a report that has been designated as optimized for TAPUR participation are preferred, but not required. The genomic or IHC test used to qualify a patient for participation in TAPUR may have been performed on any specimen of the patient's tumor obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is performed in a laboratory that meets the criteria described above.
- •Ability to understand and the willingness to sign a written informed consent/assent document.
- •Have a tumor genomic profile for which single agent treatment with one of the FDA approved targeted anti-cancer drugs included in this study has potential clinical benefit based on the criteria described in protocol.
- •For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
- •Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study or if she is the partner of a male participant in this study and becomes pregnant while he is participating in this study, she should inform her or her partner's treating physician immediately as well as her obstetrician. Female study patients who become pregnant must immediately discontinue treatment with any study therapy. Male patients should avoid impregnating a female partner. Male study patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and for a specified amount of time the last dose of study treatment, or completely abstain from sexual intercourse.
- •Note: TAPUR does not explicitly exclude any type of solid tumor, but the patient must have measurable and evaluable disease per RECIST v1.
- •Exclusion Criteria:
- •Patients whose disease is not measurable or cannot be assessed by radiographic imaging or physical examination (e.g., elevated serum tumor marker only) are not eligible
- •Patients with primary brain tumors or new, untreated or progressive leptomeningeal metastases are excluded
- •Patients with previously treated brain metastases or previously treated leptomeningeal disease are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within the 1 months prior to registration. All patients with previously treated brain metastases must be clinically stable for at least 1 month after completion of treatment and off steroid treatment for one month prior to study enrollment.
- •Patients with known progressive brain metastases are eligible but additional eligibility criteria apply.
- •Note: there are additional exclusion criteria that may apply
研究组 & 干预措施
Group 5 (CSF1R,PDGFR,VEGFR)
Participants receive sunitinib - dosage, frequency and duration per label; acceptable genomic matches include CSF1R, PDGFR, VEGFR1/2/3, KIT, FLT-3, RET, FGFR1/2/3, VHL amplifications or mutations
干预措施: Sunitinib (Drug)
Group 24 (ERBB2)
Participants receive tucatinib plus trastuzumab SC - dosage, frequency and duration per label; acceptable genomic matches include ERBB2 amplification or overexpression, and specific ERBB2 mutations
干预措施: Tucatinib plus Trastuzumab Subcutaneous (SC) (Drug)
Group 21 (BRCA1/2, PALB2, ATM, and others)
Participants receive atezolizumab plus talazoparib - dosage, frequency and duration per label; acceptable genomic matches include germline or somatic mutations in BRCA1/2, PALB2, ATM, ATR, CHEK2, FANCA, RAD51C, NBN, MLH1, MRE11A, CDK12; positive genomic instability score reported on the Myriad MyChoice CDx test; or Genomic Loss of Heterozygosity (LOH) Score above threshold as reported on a FoundationOne CDx test or another qualifying test for TAPUR with MTB approval
干预措施: Atezolizumab and Talazoparib (Drug)
Group 27 (ERBB2 amplification, ERBB2 (HER2) IHC2+ or IHC3+ overexpression)
Participants receive Fam-trastuzumab deruxtecan-nxki (ENHERTU®) - dosage, frequency and duration per label; acceptable genomic matches include ERBB2 amplification, For NSCLC Only-ERBB2 (HER2) IHC2+ or IHC3+ overexpression without ERBB2 amplification)
干预措施: Fam-Trastuzumab Deruxtecan-Nxki (TDxD) (Drug)
Group 16 (MSI-H, high mutational load and others)
Participants receive nivolumab and ipilimumab - dosage, frequency and duration per label; acceptable genomic matches include MSI high status, high tumor mutational burden, MLH1, MSH2/6, PMS2, EPCAM mutations, specific POLE or POLD1 mutations, BRCA1/2, ATM, MSH3, PMS1, MLH3, EXO1, RFC1/2/3/4/5, PCNA, RPA1/2/3/4, and SSBP1 loss of function mutations
干预措施: Nivolumab and Ipilimumab (Drug)
Group 6 (mTOR, TSC)
Participants receive temsirolimus - dosage, frequency and duration per label; acceptable genomic matches include mTOR, TSC1/2, AKT1 mutations
干预措施: Temsirolimus (Drug)
Group 8 (ERBB2)
Participants receive trastuzumab and pertuzumab - dosage, frequency and duration per label; acceptable genomic matches include ERBB2 amplification or overexpression, and specific ERBB2 mutations
干预措施: Trastuzumab and Pertuzumab (Drug)
Group 9 (BRAF V600E/D/K/R)
Participants receive vemurafenib and cobimetinib - dosage, frequency and duration per label; acceptable genomic matches include BRAF V600E/D/K/R mutations
干预措施: Vemurafenib and Cobimetinib (Drug)
Group 17 (CDKN2A, CDK4, CDK6)
Participants receive abemaciclib - dosage, frequency and duration per label; acceptable genomic matches include CDKN2A loss or mutation, CDK4, CDK6 amplifications, CDKN2B loss or mutation
干预措施: Abemaciclib (Drug)
Group 19 (BRCA1/2, PALB2)
Participants receive talazoparib - dosage, frequency and duration per label; acceptable genomic matches include germline or somatic BRCA1/2 and PALB2 mutations
干预措施: Talazoparib (Drug)
Group 14 (BRCA1/2; ATM)
Participants receive olaparib - dosage, frequency and duration per label; acceptable genomic matches include germline or somatic BRCA1/2 inactivating mutations; ATM mutations or deletions
干预措施: Olaparib (Drug)
Group 25
Participants receive futibatinib- dosage, frequency and duration per label; acceptable genomic matches include FGFR 1,2,3,4 fusion (or other rearrangement) or mutation
干预措施: Futibatinib (Drug)
Group 26 (BRAF V600 E mutation )
Participants receive Dabrafenib plus Trametinib - dosage, frequency and duration per label; acceptable genomic matches include BRAF V600 E mutation .
干预措施: Dabrafenib plus Trametinib (Drug)
结局指标
主要结局
Objective Response Rate defined as % of participants in a cohort with complete or partial response or with stable disease according to standard response criteria
时间窗: Assessed at 16 weeks of treatment
Each cohort includes participants with the same tumor type, genomic variant and study drug. For solid tumors, the Response Evaluation Criteria for Solid Tumors (RECIST) criteria will be used, for non-Hodgkin Lymphoma, the Lugano Criteria will be used, and for multiple myeloma, the International Uniform Response Criteria for Multiple Myeloma will be used.
次要结局
- Overall survival (OS)(Duration of survival from registration on study until death from any cause, assessed throughout end of study, up to 3 years)