Trial Title:
Organoid-based Functional Precision Therapy for Advanced Breast Cancer
NCT ID:
NCT06102824
Condition:
HER2-negative Breast Cancer
Advanced Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Carboplatin
Gemcitabine
Capecitabine
Trastuzumab
Vinorelbine
Taxane
Sacituzumab govitecan
Trastuzumab deruxtecan
Conditions: Keywords:
HER2-negative
Advanced breast cancer
Patient-derived organoids
Precision medicine
Randomized
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Organoid-guided treatment
Description:
The drugs predicted to be the most sensitive through organoid drug sensitivity screening.
The drugs selected for sensitivity screening are from the following options: taxane,
anthracycline, 5-fluorouracil, gemcitabine, vinorelbine, eribulin, utidelone,
carboplatin, sacituzumab govitecan, and trastuzumab deruxtecan (for HER2-low patients).
Arm group label:
Organoid-guided treatment
Intervention type:
Drug
Intervention name:
Taxane
Description:
Albumin-bound paclitaxel 260mg/m2, IV, q3w, or 100-125mg/m2, IV, days 1, 8, and 15, q4w
OR Liposomal paclitaxel 175mg/m2, IV, q3w
Arm group label:
Treatment of physician's choice
Other name:
Abraxane, Lipusu
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
1000-1250mg/m2, PO, bid, days1-14, q3w
Arm group label:
Treatment of physician's choice
Other name:
Xeloda
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
800-1200mg/m2, IV, days 1, 8, q3w
Arm group label:
Treatment of physician's choice
Other name:
Gemzar
Intervention type:
Drug
Intervention name:
Vinorelbine
Description:
20-35mg/m2, IV, days 1 and 8, q3w
Arm group label:
Treatment of physician's choice
Other name:
Navelbine
Intervention type:
Drug
Intervention name:
Eribulin
Description:
1.4mg/m2, IV, days 1 and 8, q3w
Arm group label:
Treatment of physician's choice
Other name:
Halaven
Intervention type:
Drug
Intervention name:
Anthracycline
Description:
Liposomal doxorubicin 50mg/m2, IV, q3w OR Liposomal doxorubicin 40mg/m2+Cyclophosphamide
600mg/m2, IV, q3w
Arm group label:
Treatment of physician's choice
Other name:
Doxil, Lipodox
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin AUC 6, IV, q3w or q4w OR Carboplatin AUC 2+Gemcitabine 1000mg/m2, IV, days 1
and 8, q3w OR Carboplatin AUC 2+Albumin-bound paclitaxel 125mg/m2, IV, days 1 and 8, q3w
Arm group label:
Treatment of physician's choice
Other name:
Paraplatin
Intervention type:
Drug
Intervention name:
Utidelone
Description:
30mg/m2, IV, once per day on days 1-5, q3w
Arm group label:
Treatment of physician's choice
Other name:
UTD1
Intervention type:
Drug
Intervention name:
Trastuzumab deruxtecan
Description:
5.4mg/kg, IV, q3w
Arm group label:
Treatment of physician's choice
Other name:
Enhertu
Intervention type:
Drug
Intervention name:
Sacituzumab govitecan
Description:
10mg/kg, IV, days 1 and 8, q3w
Arm group label:
Treatment of physician's choice
Other name:
Trodelvy
Summary:
This is a phase II, multicenter, open-label, randomized controlled trial to compare the
efficacy of organoid-guided treatment (OGT) to treatment of physician's choice (TPC) in
previously treated, HER2-negative locally advanced or metastatic breast cancer. The study
will seek to provide evidence for utilizing patient-derived organoid (PDO) model to
personalize treatment strategies and inform clinical care for advanced breast cancer.
Subjects randomized to the OGT group will undergo PDO generation and receive treatment
dictated by subsequent PDO drug sensitivity screening. Subjects randomized to the TPC
group will receive empirical therapy as selected by the treating physician.
Detailed description:
Treatment for advanced-stage breast cancer has long been challenging. Genomic-based
precision medicine was able to facilitate treatment selection in some patients, but there
were considerable instances where genomic profiling failed to assign effective
interventions or patients exhibited refractoriness to the drugs nominated by genomic
alterations. Patient-derived organoids (PDOs) represent a tractable tool that may
compensate for the drawbacks of genomic medicine to identify therapeutic opportunities in
rare or metastatic cancers. Previous research has demonstrated that PDOs displayed strong
biological fidelity to their original tumors and functional precision medicine based on
PDO drug screening could confer survival benefits in breast cancer patients.
This multicenter, open-label, randomized phase II trial aims to investigate the safety
and efficacy of organoid-guided treatment (OGT) versus treatment of physician's choice
(TPC) in previously treated, HER2-negative locally advanced or metastatic breast cancer.
Randomization will be stratified by hormone receptor status and prior chemotherapy for
the advanced or metastatic disease. Subjects in the OGT group will receive treatment
predicted to be the most efficacious by the PDO drug sensitivity screening, and subjects
in the TPC group will receive treatment selected by the treating physician. Treatments
tested in PDO drug screening or chosen by the treating physician will be guided by NCCN
guidelines. Treatment that subjects have previously received before randomization is no
longer subjected to PDO sensitivity screening. This study will provide valuable evidence
on the real-time application of PDOs in the context of clinical care.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Must be competent and able to comprehend, sign, and date a written informed consent
form (ICF) before performance of any study-specific procedures or tests.
2. Men or women ≥18 years old.
3. Pathologically documented unresectable locally advanced or metastatic breast cancer
that:
3.1 Confirmed as HER2-negative status, defined as IHC 0, IHC 1+, or IHC 2+/ISH-
according to American Society of Clinical Oncology College of American Pathologists
(ASCO/CAP) guidelines evaluated at a local laboratory.
3.2 Is HR-positive or HR-negative. Positive for estrogen receptor or progesterone
receptor if a finding of ≥1% of tumor cell nuclei is immunoreactive according to
ASCO/CAP guidelines.
3.3 Has been treated with at least 1 prior line of systemic therapy in the advanced
or metastatic setting. If >10% ER expression, the subject should have been treated
with a CDK4/6 inhibitor. If recurrence occurred within 6 months of adjuvant
chemotherapy, adjuvant therapy would count as 1 line of systemic therapy. If
recurrence occurred within 12 months of adjuvant CDK4/6 inhibitor and endocrine
therapy, adjuvant therapy would count as 1 line of systemic therapy.
4. Documented radiologic progression (during or after most recent treatment).
5. Presence of at least 1 measurable lesion based on computed tomography (CT) or
magnetic resonance imaging (MRI) per RECIST 1.1
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
7. All subjects must have a recent tumor sample after the most recent treatment regimen
or agree to undergo a tissue biopsy prior to randomization.
8. No visceral crisis.
9. Life expectancy of ≥ 6 months as assessed by the treating investigator.
10. Complete all required baseline laboratory tests and imaging examinations within 28
days before randomization.
11. Normal organ and bone marrow function measured within 28 days prior to
administration of study treatment.
12. Male and female subjects of reproductive/childbearing potential must have a
documented negative pregnancy test within 2 weeks prior to randomization and agree
to acceptable birth control (non-hormonal) during and up to 6 months after trial
therapy.
Subjects must satisfy all of the following additional criteria to be included in the OGT
group:
1. No absolute contraindication for invasive procedures to obtain samples for organoid
generation.
2. Sufficient material for organoid generation: biopsied samples (length>1cm, 2-3
pieces), surgically resected samples (>1cm×1cm×0.5cm, weight>200mg), malignant
effusion samples collected by thoracentesis, abdominocentesis or lumbar puncture
(pleural fluid>50mL, ascites>50mL, cerebrospinal fluid≥4 tubes with each tube ≥4mL).
3. Successful acquisition of a solid tumor biopsy sample containing ≥ 20% tumor
content, or malignant effusion sample (e.g., pleural, or pericardial effusion or
ascites) confirmed to contain malignant cells.
Exclusion Criteria:
1. Ineligible for all 5 of the study treatments either because of previously having
received treatment in the advanced or metastatic setting or having a
contraindication to treatment.
2. Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or
suspected deleterious.
3. Known active central nervous system metastases, as indicated by clinical symptoms,
cerebral edema, and/or progressive growth (patients with history of CNS metastases
or spinal cord compression are eligible if they are clinically and radiologically
stable for at least 4 weeks before first dose of trial treatment and have not
required high-dose steroid treatment in the last 4 weeks).
4. Inflammatory breast cancer.
5. Has a history of severe hypersensitivity reactions to either the drug substances or
inactive ingredients in the drug product.
6. Major surgery within 3 weeks of starting study treatment: patients must have
recovered from any effects of any major surgery.
7. Systemic treatment with anticancer therapy, antibody-based therapy, hormonal
therapy, or radiotherapy within 3 weeks before study treatment.
8. Participation in a therapeutic clinical study within 3 weeks before study treatment,
or current participation in other investigational procedures.
9. Has multiple primary malignancies within 3 years, except adequately resected
nonmelanoma skin cancer, curatively treated in situ disease, or contralateral breast
cancer.
10. Has unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia) not yet resolved to Grade ≤1 or baseline.
11. Substance abuse or medical conditions such as clinically significant cardiac or
pulmonary diseases or psychological conditions, that would, in the opinion of the
Investigator, increase the safety risk to the subject or interfere with the
subject's participation in the clinical study or evaluation of the clinical study
results.
12. Has known human immunodeficiency virus infection or active hepatitis B or C
infection.
13. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
14. Has gastrointestinal disorders likely to interfere with absorption of the study
medication.
15. Is pregnant or breastfeeding or planning to become pregnant.
16. Any concurrent condition which in the Investigator's opinion makes it inappropriate
for the patient to participate in the trial or which would jeopardize compliance
with the protocol.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Guangdong Provincial People's Hospital
Address:
City:
Guangzhou
Zip:
510080
Country:
China
Status:
Recruiting
Contact:
Last name:
Kun Wang, M.D.
Phone:
02083827812
Email:
wangkun@gdph.org.cn
Start date:
September 25, 2024
Completion date:
June 30, 2028
Lead sponsor:
Agency:
Guangdong Provincial People's Hospital
Agency class:
Other
Collaborator:
Agency:
First Affiliated Hospital, Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
Shantou Central Hospital
Agency class:
Other
Source:
Guangdong Provincial People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06102824
