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

Solid Organ Malignancies Clinical Trial

— DRUID  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05719428
• Other study ID #: 2022/00653
• Status: Recruiting
• Phase: Phase 2
• Start date: August 28, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: National University Hospital, Singapore
• Contact: Robert John Walsh
• Phone: 69082222
• Email: robert_walsh[@]nuhs.edu.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Organ Malignancies

Intervention

Other:
• 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.

Locations

Country	Name	City	State
Singapore	Department of Hematology-Oncology, National University Hospital	Singapore

Sponsors (3)

Lead Sponsor	Collaborator
National University Hospital, Singapore	Cancer Science Institute, National University of Singapore, School of Computing, National University of Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (8)

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. — View Citation

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. — View Citation

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 A, Choi HG, Chang JW, Baselga J, Stamenkovic I, Engelman JA, Sharma SV, Delattre O, Saez-Rodriguez J, Gray NS, Settleman J, Futreal PA, Haber DA, Stratton MR, Ramaswamy S, McDermott U, Benes CH. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 2012 Mar 28;483(7391):570-5. doi: 10.1038/nature11005. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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, Stewart L, Baldi T, Mullaney KA, Al-Ahmadie H, Vakiani E, Abeshouse AA, Penson AV, Jonsson P, Camacho N, Chang MT, Won HH, Gross BE, Kundra R, Heins ZJ, Chen HW, Phillips S, Zhang H, Wang J, Ochoa A, Wills J, Eubank M, Thomas SB, Gardos SM, Reales DN, Galle J, Durany R, Cambria R, Abida W, Cercek A, Feldman DR, Gounder MM, Hakimi AA, Harding JJ, Iyer G, Janjigian YY, Jordan EJ, Kelly CM, Lowery MA, Morris LGT, Omuro AM, Raj N, Razavi P, Shoushtari AN, Shukla N, Soumerai TE, Varghese AM, Yaeger R, Coleman J, Bochner B, Riely GJ, Saltz LB, Scher HI, Sabbatini PJ, Robson ME, Klimstra DS, Taylor BS, Baselga J, Schultz N, Hyman DM, Arcila ME, Solit DB, Ladanyi M, Berger MF. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017 Jun;23(6):703-713. doi: 10.1038/nm.4333. Epub 2017 May 8. Erratum In: Nat Med. 2017 Aug 4;23 (8):1004. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Defined as patient exhibiting a best study response of complete or partial clinical response based on radiological imaging per RECIST 1.1 criteria.	10 months
Secondary	Clinical benefit	Defined as presence of best study response of complete or partial response or stable disease for at least 24 weeks (based on RECIST 1.1 criteria).	10 months
Secondary	Progression free survival	Defined as the time from the date of study enrolment to the first date of documented disease progression.	From enrolment till disease progression or date of death or final follow-up visit (1 year).