Back to results

Selecting Chemotherapy With High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients With Refractory Solid Tumours (SCORE)

Primary Purpose

Organoids, HNSCC, Epithelial Ovarian Cancer

Status

Unknown status

Phase

Not Applicable

Locations

Singapore

Study Type

Interventional

Intervention

Tumor Core Biopsy

Blood sampling

About this trial

This is an interventional diagnostic trial for Organoids focused on measuring Organoid

Eligibility Criteria

21 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

(ii) Hepatic:

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

(iii) Renal:

◦Creatinine ≤ 1.5x ULN

Signed informed consent from patient or legal representative.
Able to comply with study-related procedures.

Exclusion Criteria:

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.

Sites / Locations

National University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cancer patient

Arm Description

Histological or cytological diagnosis of head and neck squamous cell carcinoma (HNSCC), colorectal, breast or epithelial ovarian cancer.

Outcomes

Primary Outcome Measures

Overall radiological response rate

Measured by RECIST of the entire study cohort

Correlation between patient genotype, tumor biomarkers and blood biomarkers with clinical outcome

Clinical Outcome include Radiological response, progression-free survival, grade 3-4 toxicities

Secondary Outcome Measures

Full Information

NCT ID

NCT04279509

First Posted

February 10, 2020

Last Updated

September 8, 2020

Sponsor

National University Hospital, Singapore

1. Study Identification

Unique Protocol Identification Number

NCT04279509

Brief Title

Selecting Chemotherapy With High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients With Refractory Solid Tumours (SCORE)

Official Title

Selecting Chemotherapy With High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients With Refractory Solid Tumours (SCORE)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Unknown status

Study Start Date

May 29, 2019 (Actual)

Primary Completion Date

May 2021 (Anticipated)

Study Completion Date

May 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National University Hospital, Singapore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Organoids, HNSCC, Epithelial Ovarian Cancer, Colorectal Cancer

Keywords

Organoid

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cancer patient

Arm Type

Experimental

Arm Description

Histological or cytological diagnosis of head and neck squamous cell carcinoma (HNSCC), colorectal, breast or epithelial ovarian cancer.

Intervention Type

Procedure

Intervention Name(s)

Tumor Core Biopsy

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Blood sampling

Intervention Description

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).

Primary Outcome Measure Information:

Title

Overall radiological response rate

Description

Measured by RECIST of the entire study cohort

Time Frame

2 years

Title

Correlation between patient genotype, tumor biomarkers and blood biomarkers with clinical outcome

Description

Clinical Outcome include Radiological response, progression-free survival, grade 3-4 toxicities

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 (ii) Hepatic: Bilirubin ≤ 1.5 x upper limit of normal (ULN), ALT or AST ≤ 2.5x ULN,(or ≤ 5X with liver metastases) (iii) Renal: ◦Creatinine ≤ 1.5x ULN Signed informed consent from patient or legal representative. Able to comply with study-related procedures. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Soo Chin Lee

Phone

6779 5555

soo_chin_lee@nuhs.edu.sg

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Soo Chin Lee

Organizational Affiliation

National University Hospital, Singapore

Official's Role

Principal Investigator

Facility Information:

Facility Name

National University Hospital

City

Singapore

Country

Singapore

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Soo Chin Lee

Phone

6779 5555

soo_chin_lee@nuhs.edu.sg

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

19351829

Citation

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.

Results Reference

background

PubMed Identifier

25877891

Citation

Jones 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.

Results Reference

result

Learn more about this trial

Selecting Chemotherapy With High-throughput Drug Screen Assay Using Patient Derived Organoids in Patients With Refractory Solid Tumours (SCORE)

We'll reach out to this number within 24 hrs