TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

Официальное название

Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Обзор

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). \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\* 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. \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*

Подробное описание

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.

Вмешательства

• Препарат Palbociclib
  drug
• Препарат Sunitinib
  drug
• Препарат Temsirolimus
  drug
• Препарат Trastuzumab and Pertuzumab
  drug
• Препарат Vemurafenib and Cobimetinib
  drug
• Препарат Regorafenib
  drug
• Препарат Olaparib
  drug
• Препарат Nivolumab and Ipilimumab
  drug
• Препарат Abemaciclib
  drug
• Препарат Talazoparib
  drug

Первичные конечные точки

• Objective Response Rate defined as % of participants in a cohort with complete or partial response or with stable disease according to standard response criteria [Срок оценки: Assessed at 16 weeks of treatment]

Вторичные конечные точки (1)

• Overall survival (OS) [Срок оценки: Duration of survival from registration on study until death from any cause, assessed throughout end of study, up to 3 years]

Критерии участия

Критерии включения

• 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
• 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/exclusion criteria specified in the protocol appendix for each agent will take precedence for this and all inclusion criteria:

• Absolute neutrophil count ≥ 1.5 x 106/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 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), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patient's whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only, bone-only disease without an identifiable soft tissue component, or patients with only assessable non-measurable disease) are NOT eligible.
• 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 drug, 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 v1.1.

Критерии исключения

• 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 are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within the 3 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 174 центра

• University of Alabama at Birmingham Comprehensive Cancer Center — Birmingham
• Cancer Treatment Centers of America-Phoenix — Phoenix
• Sutter Auburn — Auburn
• Sutter Alta Bates — Berkeley
• The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate — Los Angeles
• Kaiser Permanente - Oakland Medical Center — Oakland
• Sutter Palo Alto Medical Foundation: Palo Alto — Palo Alto
• Kaiser Permanente - Roseville Medical Center — Roseville
• … и ещё 166 центров

Пуэрто-Рико · 7 центров

Список центров уточняется — проверьте первичный протокол.

Публикации

• Veljovich DS, Rothe M, Garrett-Mayer E, Ali-Ahmad HM, Naumann RW, Siedel J, Chan JK, Gregory A, Pisick E, Adesunloye B, Arend RC, Bell M, Frimer M, Tawfik B, Thota R, Tsimberidou AM, Mangat PK, Hinshaw DC, Gregory A, Grantham GN, Halabi S, Schilsky RL. Palbociclib in Patients With Ovarian Cancer With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study. JCO PMID 42456088
• Cobain EF, Rothe M, Garrett-Mayer E, Cannon TL, Chan JK, Mileham KF, Adesunloye B, Calfa CJ, Alese OB, Butler KY, Dib EG, Pisick E, Bell M, Klute KA, Mehmi I, Meric-Bernstam F, Mangat PK, Hinshaw DC, Gregory A, Grantham GN, Halabi S, Schilsky RL. Nivolumab Plus Ipilimumab in Patients With Solid Tumors With High Tumor Mutation Burden: Results From the Targeted Agent and Profiling Utilization Regist PMID 42060861
• Pisick E, Rothe M, Garrett-Mayer E, Srkalovic G, Chan JK, Calfa CJ, Leath CA 3rd, Marr AS, Gold PJ, Crane EK, Moyers JT, Yost Butler K, Gaba A, Thota R, Harnden KK, Alese OB, Jain A, Rueter J, Gill S, George TJ, Frimer M, Kayali F, Mangat PK, Hinshaw DC, Gregory A, Grantham GN, Halabi S, Schilsky RL. Temsirolimus in Patients With Solid Tumors With PIK3CA Mutations: Results From the Targeted Agent PMID 42018965
• Carrizosa DR, Rothe M, Mangat PK, Garrett-Mayer E, Behl D, Adesunloye B, Pisick E, Beekman KW, Dotan E, Akce M, Alese OB, Sahai V, Klute KA, Aragon-Ching JB, Cooper KA, Thota R, Meric-Bernstam F, Hosein PJ, Maestas EC, Moyers JT, Powell S, Zhao S, Hobbs E, Rueter J, Sohal DPS, Taylor MA, Hinshaw DC, Gregory A, Grantham GN, Halabi S, Schilsky RL. Olaparib in Patients With Solid Tumors With ATM Alte PMID 41538762
• Al Baghdadi T, Rothe M, Mangat PK, Garrett-Mayer E, Crysler OV, Mileham KF, Farrington LC, Adesunloye B, Dublis SA, Astsaturov I, Calfa CJ, Bleeker J, Khalil M, Thota R, Cannon TL, Alese OB, Gold PJ, Hafez N, Baron AD, Meric-Bernstam F, Hobbs E, Marr AS, Rueter J, Tawfik B, Hinshaw DC, Gregory A, Grantham GN, Halabi S, Schilsky RL. Olaparib in Patients With Solid Tumors With BRCA1/2 Alterations: R PMID 41100773
• Mangat PK, Kirkwood MK, Hinshaw DC, Garrett-Mayer E, Schilsky RL. Prevalence of targetable genomic alterations among a diverse population participating in the ASCO TAPUR Study. NPJ Precis Oncol. 2025 Jul 3;9(1):222. doi: 10.1038/s41698-025-00962-1. PMID 40610648
• Worden FP, Pisick E, Rothe M, Mangat PK, Garrett-Mayer E, Khalil MF, Carrizosa DR, Bauman JR, Leidner RS, Duvivier HL, Fu S, Park MS, Yost KJ, Calfa CJ, Marr AS, Balmanoukian AS, Behl D, Cannon TL, Nabell L, Powell SF, Thota R, Hinshaw DC, Gregory A, Grantham GN, Halabi S, Schilsky RL. Palbociclib in Patients With Head and Neck Cancer and Other Tumors With CDKN2A Alterations: Results From the Targ PMID 39413339
• Schuetze S, Rothe M, Mangat PK, Garrett-Mayer E, Meric-Bernstam F, Calfa CJ, Farrington LC, Livingston MB, Wentzel K, Behl D, Kier Y, Marr AS, von Mehren M, Press JZ, Thota R, Grantham GN, Gregory A, Hinshaw DC, Halabi S, Schilsky RL. Palbociclib in Patients With Soft Tissue Sarcoma With CDK4 Amplifications: Results From the Targeted Agent and Profiling Utilization Registry Study. JCO Precis Oncol PMID 39013131

Идентификаторы

NCT: NCT02693535 · Pro00014171

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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