Quadratic Phenotypic Optimisation Platform (QPOP) Utilisation to Enhance Selection of Patient Therapy Through Patient Derived Organoids in Breast Cancer

NCT05177432 | Unknown Phase 1

• 1 other identifier: BR02/03/21
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Based on proof-of-concept study, the investigators hypothesise that the QPOP prediction model can be further extended into use in solid tumors. Using breast cancer as a model, the investigators intend to investigate the feasibility of QPOP as a clinical decision support platform to identify patient-specific drug combinations across a range of breast cancer patients. The investigators propose a pilot phase I clinical study to test the feasibility of using QPOP to guide therapy in patients with advanced breast cancer.

Conditions

Breast Cancer

Keywords

QPOP; Enhance Selection; Patient Therapy; Patient Derived Organoids; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate measured by RECIST 1.1 criteria to anti-cancer therapy selected by QPOP (prospective analysis).

  3 years

Secondary Outcomes (4)

• Clinical benefit rate as determined by proportion of patients with complete response, partial response or stable disease as best response on RECIST 1.1 criteria (prospective analysis)

  3 years

• Progression-free survival of QPOP-guided therapy as measured by RECIST 1.1 criteria (prospective analysis)

  3 years

• Correlating QPOP prediction score of immediate past line of therapy and objective response rate to that therapy (retrospective correlative analysis)

  3 years

• Correlating objective response rate (ORR) measured by RECIST v1.1 of the tumor lesion biopsied for QPOP analyses with QPOP guided therapy (retrospective correlative analysis)

  3 years

Study Arms (1)

QPOP-based drug screen assay using patient tumour-derived organoids

EXPERIMENTAL

Patients with Histological confirmed breast carcinoma of any subtype (any estrogen receptor, progesterone receptor and HER2 receptor status) with at least 1 tumour lesion (primary or metastatic) amendable to fresh biopsy and measurable based on RECIST 1.1 criteria will undergo biopsy to obtain a sample of cancer tissue that will be used to generate Patient Derived Organoids (PDOs). Patients' cells will be subjected to testing with 10-12 anti-cancer drugs and a table for treatment sensitivity to each drug will be derived after 8 to 12 weeks of treatment in the laboratory. Results will be reviewed at an expert panel discussion to decide on the most suitable anti-cancer drug treatment

Device: QPOP

Interventions

QPOP DEVICE

QPOP will be used as a clinical decision support platform to identity suitable patient-specific drug combinations across a range of breast cancer patients, which are derived from drug sensitivity tests using patient-derived materials.

QPOP-based drug screen assay using patient tumour-derived organoids

Eligibility Criteria

• Age: 21 Years - 99 Years
• Gender Eligibility Details: Breast cancer study - 99.9% breast cancer patients are female. Male breast cancer is extremely rare and we do not intend to include this rare population
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Age \>= 21 years.
• Histological confirmed breast carcinoma of any subtype (any estrogen receptor, progesterone receptor and HER2 receptor status)
• ECOG 0-1.
• At least 1 tumour lesion (primary or metastatic) amenable to fresh biopsy
• 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 1 line of palliative systemic therapy
• Expected adequate organ function (bone marrow, hepatic, renal) after recovering from treatment-induced acute toxicities at the time of study treatment.
• Signed informed consent from patient or legal representative.
• Able to comply with study-related procedures.
• Patients will be excluded from the study for any of the following reasons:
• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital Singapore

Singapore, Singapore

RECRUITING

Related Publications (11)

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  PMID: 12218176 RESULT

• Goodspeed A, Heiser LM, Gray JW, Costello JC. Tumor-Derived Cell Lines as Molecular Models of Cancer Pharmacogenomics. Mol Cancer Res. 2016 Jan;14(1):3-13. doi: 10.1158/1541-7786.MCR-15-0189. Epub 2015 Aug 6.

  PMID: 26248648 RESULT

• Sachs N, de Ligt J, Kopper O, Gogola E, Bounova G, Weeber F, Balgobind AV, Wind K, Gracanin A, Begthel H, Korving J, van Boxtel R, Duarte AA, Lelieveld D, van Hoeck A, Ernst RF, Blokzijl F, Nijman IJ, Hoogstraat M, van de Ven M, Egan DA, Zinzalla V, Moll J, Boj SF, Voest EE, Wessels L, van Diest PJ, Rottenberg S, Vries RGJ, Cuppen E, Clevers H. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. Cell. 2018 Jan 11;172(1-2):373-386.e10. doi: 10.1016/j.cell.2017.11.010. Epub 2017 Dec 7.

  PMID: 29224780 RESULT

• Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R, Rata M, Koh DM, Tunariu N, Collins D, Hulkki-Wilson S, Ragulan C, Spiteri I, Moorcraft SY, Chau I, Rao S, Watkins D, Fotiadis N, Bali M, Darvish-Damavandi M, Lote H, Eltahir Z, Smyth EC, Begum R, Clarke PA, Hahne JC, Dowsett M, de Bono J, Workman P, Sadanandam A, Fassan M, Sansom OJ, Eccles S, Starling N, Braconi C, Sottoriva A, Robinson SP, Cunningham D, Valeri N. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018 Feb 23;359(6378):920-926. doi: 10.1126/science.aao2774.

  PMID: 29472484 RESULT

• Shaughnessy JD Jr, Qu P, Usmani S, Heuck CJ, Zhang Q, Zhou Y, Tian E, Hanamura I, van Rhee F, Anaissie E, Epstein J, Nair B, Stephens O, Williams R, Waheed S, Alsayed Y, Crowley J, Barlogie B. Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3. Blood. 2011 Sep 29;118(13):3512-24. doi: 10.1182/blood-2010-12-328252. Epub 2011 May 31.

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• de Mel S, Rashid MBM, Zhang XY, Goh J, Lee CT, Poon LM, Chan EHL, Liu X, Chng WJ, Chee YL, Lee J, Yuen YC, Lim JQ, Chia BKH, Laurensia Y, Huang D, Pang WL, Cheah DMZ, Wong EKY, Ong CK, Tang T, Lim ST, Ng SB, Tan SY, Loi HY, Tan LK, Chow EK, Jeyasekharan AD. Application of an ex-vivo drug sensitivity platform towards achieving complete remission in a refractory T-cell lymphoma. Blood Cancer J. 2020 Jan 27;10(1):9. doi: 10.1038/s41408-020-0276-7. No abstract available.

  PMID: 31988286 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Soo Chin Lee

CONTACT

65 6772 4629; soo_chin_lee@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-centre study based on the Simon 2-stage optimal design: 9 patients will be enrolled initially. The study will be expanded to a further 14 patients (Stage II) if 2 or more patients enrolled in stage I of the study achieve an objective response (of \>35% ) with the chemotherapeutic agent selected by the drug screen assay. Accounting for 10% attrition rate, a total of 26 evaluable patients will be included in both stages of study. QPOP-based drug screen assay will be used as a clinical decision platform to identify patient-specific drug combinations across a range of breast cancer patients.

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: January 4, 2022
• Study Start: December 6, 2021
• Primary Completion: January 3, 2025
• Study Completion: December 31, 2025
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)