OrganoidsNCT04279509
Selecting Chemotherapy With High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients With Refractory Solid Tumours (SCORE)
A study testing Tumor Core Biopsy and Blood sampling in people with Organoids and HNSCC, run by National University Hospital, Singapore at 1 site in Singapore.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Organoids, HNSCC, Epithelial Ovarian Cancer
- What is being tested?
- Tumor Core Biopsy and Blood sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteSingapore
- Study dates
- 29 May 2019to May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- 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
- Hepatic:
- Bilirubin ≤ 1.5 x upper limit of normal (ULN),
- ALT or AST ≤ 2.5x ULN,(or ≤ 5X with liver metastases)
- Renal:
- ◦Creatinine ≤ 1.5x ULN
- Signed informed consent from patient or legal representative.
- Able to comply with study-related procedures.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore
Soo Chin Lee, 6779 5555, soo_chin_lee@nuhs.edu.sg
About this study
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.
Read the detailed description
Investigators hypothesize that high-throughput screening on patient-derived tumour organoids can be used as an adjunct tool to aid treatment selection in patients with cancer. Using the IRS, drugs with high IRS (defined as a score of 70% and above) will have a high probability of inducing objective response (either a complete or partial response by RECIST criteria) in patients with refractory cancers. Conversely, IRS of drugs for which the patients have been treated and experienced clinical progression on will be low (defined as a score of 50% or below).
Primary Objectives
-To prospectively determine if a high-throughput drug screen assay using patient tumour-derived organoids can accurately select a chemotherapeutic agent that results in objective response in patients with refractory solid tumours
Secondary Objectives
- To assess the IRS measured on tumour-derived organoid drug screen assay of chemotherapeutic agents to which patients had previously progressed on clinically
- To assess changes in IRS pre and post-chemotherapy treatment
- Conditions
- Organoids, HNSCC, Epithelial Ovarian Cancer, Colorectal Cancer
- Being tested
- Tumor Core Biopsy, Blood sampling
- Keywords
- Organoid
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Ovarian Epithelial, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor Core BiopsyProcedure or surgery
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.
Blood samplingProcedure or surgery
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).
| Study group | Role | What they receive |
|---|---|---|
| Cancer patient | Experimental | Histological or cytological diagnosis of head and neck squamous cell carcinoma (HNSCC), colorectal, breast or epithelial ovarian cancer. Receives: Procedure: Tumor Core Biopsy; Procedure: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall radiological response rate
Measured by RECIST of the entire study cohort
Measured: 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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2020
- Study start29 May 2019
- Primary completionMay 2021 (estimated)
- Study completionMay 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OrganoidsStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04279509
- Sponsor's protocol ID
- MC01/01/19
- Status last verified
- Sep 2020
- First submitted
- 10 Feb 2020
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 19351829Jones 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.
PubMed 25877891
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selecting Chemotherapy With High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients With Refractory Solid Tumours (SCORE)
- ClinicalTrials.gov ID
- NCT04279509
- Acronym / sponsor ID
- MC01/01/19
- Conditions
- Organoids, HNSCC, Epithelial Ovarian Cancer, Colorectal Cancer
- Keywords
- Organoid
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 29 May 2019 (actual)
- Primary completion
- May 2021 (estimated)
- Study completion
- May 2022 (estimated)
- First posted
- 21 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Investigators hypothesize that high-throughput screening on patient-derived tumour organoids can be used as an adjunct tool to aid treatment selection in patients with cancer. Using the IRS, drugs with high IRS (defined as a score of 70% and above) will have a high probability of inducing objective response (either a complete or partial response by RECIST criteria) in patients with refractory cancers. Conversely, IRS of drugs for which the patients have been treated and experienced clinical progression on will be low (defined as a score of 50% or below).
Primary Objectives
-To prospectively determine if a high-throughput drug screen assay using patient tumour-derived organoids can accurately select a chemotherapeutic agent that results in objective response in patients with refractory solid tumours
Secondary Objectives
- To assess the IRS measured on tumour-derived organoid drug screen assay of chemotherapeutic agents to which patients had previously progressed on clinically
- To assess changes in IRS pre and post-chemotherapy treatment
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cancer patient | Experimental | Procedure: Tumor Core Biopsy, Procedure: Blood samplingHistological or cytological diagnosis of head and neck squamous cell carcinoma (HNSCC), colorectal, breast or epithelial ovarian cancer. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tumor Core BiopsyPerformed 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. | Procedure or surgery | Cancer patient |
| Blood samplingGermline 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). | Procedure or surgery | Cancer patient |
Primary outcome
Overall radiological response rate
Time frame: 2 years
Measured by RECIST of the entire study cohort
Correlation between patient genotype, tumor biomarkers and blood biomarkers with clinical outcome
Time frame: 2 years
Clinical Outcome include Radiological response, progression-free survival, grade 3-4 toxicities
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Background: PubMed 19351829Daniel 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.
- Results publication: PubMed 25877891Jones 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Soo Chin Lee principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tumor Core Biopsy and Blood sampling in people with Organoids and HNSCC, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Soo Chin Lee (6779 5555, soo_chin_lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall radiological response rate (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04279509, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.