Selecting Chemotherapy With High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients With Refractory Solid Tumours (SCORE)
1 other identifier
interventional
35
1 country
1
Brief Summary
This is a single-centre study based on the Simon 2-stage optimax design: 12 patients will be enrolled initially (Stage I), which will then be expanded to a further 13 patients (Stage II) if 3 or more patients enrolled in stage I of the study achieve an objective response with the chemotherapeutic agent selected by the drug screen assay. A total of 25 patients will be included in both stages of study. Patients enrolled on study will undergo a fresh biopsy of tumour lesion to obtain cells that will be used to generate patient-derived tumour organoids based on the Invitrocue technology. Organoids will then be subjected to a 10-drug panel screening including: 5-fluorouracil, carboplatin, cyclophosphamide, docetaxel, doxorubicin, gemcitabine, irinotecan, oxaliplatin, paclitaxel and vinorelbine. A further 5 drugs (etoposide, ifosfamide, methotrexate, pemetrexed and topotecan) will be screened if sufficient organoids are grown from the biopsy samples within the screening period. Physicians will be informed of the results, and choice of chemotherapy will be based on an IRS score of 70% or above. If more than 1 candidate drug with IRS of 70% or above is identified, the physician will exercise his/her discretion to select the most suitable drug based on patient's comorbidities and organ function.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started May 2019
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 29, 2019
CompletedFirst Submitted
Initial submission to the registry
February 10, 2020
CompletedFirst Posted
Study publicly available on registry
February 21, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2022
CompletedSeptember 9, 2020
September 1, 2020
1.9 years
February 10, 2020
September 8, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall radiological response rate
Measured by RECIST of the entire study cohort
2 years
Correlation between patient genotype, tumor biomarkers and blood biomarkers with clinical outcome
Clinical Outcome include Radiological response, progression-free survival, grade 3-4 toxicities
2 years
Study Arms (1)
Cancer patient
EXPERIMENTALHistological or cytological diagnosis of head and neck squamous cell carcinoma (HNSCC), colorectal, breast or epithelial ovarian cancer.
Interventions
Performed up to a maximum of 3 time points - baseline upon study enrolment, at the completion of treatment, and upon disease progression. Four to six tumour core samples will be obtained at each time point. At least two tumour cores will be sent fresh to Invitrocue Pte Ltd for generation of patient-derived organoids for drug-panel screening, at least 1-2 tumour cores at each time point will be stored in formalin and paraffin-embedded for immunohistochemistry analysis of biomarkers, while the remaining 1-2 tumour cores will be stored in liquid nitrogen for subsequent DNA, RNA and protein extraction for biomarker studies including gene expression and proteomics analyses.
Germline DNA at baseline for pharmacogenetics analysis. Serial plasma samples for circulating tumour cells and biomarkers, at baseline, prior to day 1 of each cycle while on treatment, at the end of treatment (either upon disease progression or upon completion of predetermined cycles of chemotherapy).
Eligibility Criteria
You may qualify if:
- Age ≥ 21 years.
- Histological or cytological diagnosis of head and neck squamous cell carcinoma (HNSCC), colorectal, breast or epithelial ovarian cancer.
- 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.
- Able to wait at least 4 to 6 weeks before initiating the next line of anti-cancer therapy.
- Has received at least 2 line of palliative systemic therapy:
- (i) Breast cancer: must have received prior anthracyclines and taxanes in the neoadjuvant, adjuvant or palliative setting, unless either of these drugs were contraindicated due to organ dysfunction and/or comorbidities (ii) Ovarian cancer: must have received prior taxanes and platinums in the neoadjuvant, adjuvant or palliative setting (iii)HNSCC: must have received prior platinums, taxanes, and 5-fluorouracil in the neoadjuvant, adjuvant or palliative setting (iv)Colorectal cancer: must have received prior 5-fluorouracil, oxaliplatin and irinotecan in the neoadjuvant, adjuvant or palliative setting
- Adequate organ function including the following:
- (i)Bone marrow:
- Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L
- Platelets ≥100 x 109/L
- Hemoglobin ≥ 8 x 109/L
- +7 more criteria
You may not qualify if:
- Pace of cancer progression requiring commencement of anti-cancer therapy within 4 to 6 weeks.
- 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.
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National University Hospital
Singapore, Singapore
Related Publications (2)
Daniel VC, Marchionni L, Hierman JS, Rhodes JT, Devereux WL, Rudin CM, Yung R, Parmigiani G, Dorsch M, Peacock CD, Watkins DN. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res. 2009 Apr 15;69(8):3364-73. doi: 10.1158/0008-5472.CAN-08-4210. Epub 2009 Apr 7.
PMID: 19351829BACKGROUNDJones S, Anagnostou V, Lytle K, Parpart-Li S, Nesselbush M, Riley DR, Shukla M, Chesnick B, Kadan M, Papp E, Galens KG, Murphy D, Zhang T, Kann L, Sausen M, Angiuoli SV, Diaz LA Jr, Velculescu VE. Personalized genomic analyses for cancer mutation discovery and interpretation. Sci Transl Med. 2015 Apr 15;7(283):283ra53. doi: 10.1126/scitranslmed.aaa7161.
PMID: 25877891RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Soo Chin Lee
National University Hospital, Singapore
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 10, 2020
First Posted
February 21, 2020
Study Start
May 29, 2019
Primary Completion
May 1, 2021
Study Completion
May 1, 2022
Last Updated
September 9, 2020
Record last verified: 2020-09
Data Sharing
- IPD Sharing
- Will not share