Neural Network-based Treatment Decision Support Tool in Patients With Refractory Solid Organ Malignancies

Официальное название

A Phase II Trial of Neural Network-based Treatment Decision Support Tool in Patients With Refractory Solid Organ Malignancies

Обзор

DRUID is a treatment decision support tool combining predictive models and public databases related to multi-gene markers, drug response screens, gene essentiality and clinical status of drugs to provide drug recommendations personalized based on an input genomic profile. We hypothesize that DRUID analysis of patients' somatic mutational profile from NGS diagnostic platform can be used as a treatment decision support tool in patients with refractory cancer without targetable mutations.

Подробное описание

2.1. Hypothesis We hypothesize that DRUID analysis of patients' somatic mutational profile from NGS diagnostic platform can be used as a treatment decision support tool in patients with refractory cancer without targetable mutations. Using algorithm selected treatment from a panel of 60 drugs we predict an objective response rate (ORR) of ≥ 25%.

2.2. Primary Objectives

• To prospectively determine if DRUID selected therapy based on NGS diagnostic profile input can lead to objective responses in refractory solid organ malignancies.

2.3. Secondary Objectives

* To assess clinical benefit rate (complete response, partial response and stable disease for ≥ 24 weeks) * To assess progression-free and overall survival of patients treated with DRUID-guided therapy

Вмешательства

• Другое DRUID AI Program
  Patients will begin single agent therapy within 4 weeks of enrolment and continue until disease progression, maximum safe cumulative dose reached (where applicable, per standard institution practice) or unacceptable toxicity as per physician's discretion.

Первичные конечные точки

• Objective response rate (ORR) [Срок оценки: 10 months]

Вторичные конечные точки (2)

• Clinical benefit [Срок оценки: 10 months]
• Progression free survival [Срок оценки: From enrolment till disease progression or date of death or final follow-up visit (1 year).]

Критерии участия

Критерии включения

Patients may be included in the study only if they meet all of the following criteria:

• Age ≥ 21 years.
• Histological or cytological diagnosis solid organ malignancy
• Available results of comprehensive NGS panel testing performed on either tumour tissue or blood-based assay. If results are from blood-based assay, test must have been performed in the metastatic setting.
• ECOG 0-2.
• At least 1 measurable tumour lesions based on RECIST 1.1 criteria
• Estimated life expectancy of at least 12 weeks.
• Has documented progressive disease from last line of therapy.
• Has received at least 2 lines of palliative systemic therapy with no available standard therapy:
• Adequate organ function including the following:

• Bone marrow:

• Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 8 x 109/L
• Hepatic:

• Bilirubin ≤ 1.5 x upper limit of normal (ULN),
• ALT or AST ≤ 2.5x ULN, (or ≤ 5 X with liver metastases)
• Renal:

• Creatinine ≤ 1.5x ULN
• Signed informed consent from patient or legal representative.
• Able to comply with study-related procedures.

Критерии исключения

• Treatment within the last 30 days with any investigational drug.
• Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
• Major surgery within 28 days of study drug administration.
• Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Pregnancy.
• Breast feeding.
• Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• Active bleeding disorder or bleeding site.
• Non-healing wound.
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
• Symptomatic brain metastasis.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Сингапур · 1 центр

• Department of Hematology-Oncology, National University Hospital — Singapore

Публикации

• Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, Srinivasan P, Gao J, Chakravarty D, Devlin SM, Hellmann MD, Barron DA, Schram AM, Hameed M, Dogan S, Ross DS, Hechtman JF, DeLair DF, Yao J, Mandelker DL, Cheng DT, Chandramohan R, Mohanty AS, Ptashkin RN, Jayakumaran G, Prasad M, Syed MH, Rema AB, Liu ZY, Nafa K, Borsu L, Sadowska J, Casanova J, Bacares R, Kiecka IJ, Razumova A, Son JB, Stewa PMID 28481359
• Garraway LA, Verweij J, Ballman KV. Precision oncology: an overview. J Clin Oncol. 2013 May 20;31(15):1803-5. doi: 10.1200/JCO.2013.49.4799. Epub 2013 Apr 15. No abstract available. PMID 23589545
• Califano A, Alvarez MJ. The recurrent architecture of tumour initiation, progression and drug sensitivity. Nat Rev Cancer. 2017 Feb;17(2):116-130. doi: 10.1038/nrc.2016.124. Epub 2016 Dec 15. PMID 27977008
• Mariappan R, Jayagopal A, Sien HZ, Rajan V. Neural Collective Matrix Factorization for integrated analysis of heterogeneous biomedical data. Bioinformatics. 2022 Sep 30;38(19):4554-4561. doi: 10.1093/bioinformatics/btac543. PMID 35929808
• Nguyen T, Nguyen GTT, Nguyen T, Le DH. Graph Convolutional Networks for Drug Response Prediction. IEEE/ACM Trans Comput Biol Bioinform. 2022 Jan-Feb;19(1):146-154. doi: 10.1109/TCBB.2021.3060430. Epub 2022 Feb 3. PMID 33606633
• Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, Greninger P, Thompson IR, Luo X, Soares J, Liu Q, Iorio F, Surdez D, Chen L, Milano RJ, Bignell GR, Tam AT, Davies H, Stevenson JA, Barthorpe S, Lutz SR, Kogera F, Lawrence K, McLaren-Douglas A, Mitropoulos X, Mironenko T, Thi H, Richardson L, Zhou W, Jewitt F, Zhang T, O'Brien P, Boisvert JL, Price S, Hur W, Yang W, Deng X, Butler PMID 22460902
• Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J, Bolton EE. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res. 2019 Jan 8;47(D1):D1102-D1109. doi: 10.1093/nar/gky1033. PMID 30371825
• Cancer Genome Atlas Research Network; Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013 Oct;45(10):1113-20. doi: 10.1038/ng.2764. PMID 24071849

Идентификаторы

NCT: NCT05719428 · 2022/00653

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗