Organoid-based Functional Precision Therapy for Advanced Breast Cancer

NCT06102824 | Recruiting Phase 2 DMC

• 1 other identifier: 20231028
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HER2-negative Breast Cancer; Advanced Breast Cancer

Keywords

HER2-negative; Advanced breast cancer; Patient-derived organoids; Precision medicine; Randomized

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  PFS is defined as the time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression according to RECIST version 1.1 or death due to any cause. Subjects who are alive with no objective documentation of (radiographic) disease progression by the data cutoff date for PFS analysis will be censored at the date of their last evaluable tumor assessment. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

  Through study completion, with an expected average of 1 year

Secondary Outcomes (7)

• Overall survival

  Through study completion, with an expected average of 2 year

• Objective response rate

  Through study completion, with an expected average of 1 year

• Disease control rate

  Through study completion, with an expected average of 1 year

• Clinical benefit rate

  Through study completion, with an expected average of 1 year

• Duration of response

  Through study completion, with an expected average of 1 year

Study Arms (2)

Organoid-guided treatment

EXPERIMENTAL

Subjects randomized to the organoid-guided treatment (OGT) group will be treated with the drugs predicted to be the most sensitive through PDO drug sensitivity screening. Drugs that the subjects have progressed on before randomization will not be screened. The drugs selected for organoid screening are from the following options: taxane, anthracycline, 5-fluorouracil, gemcitabine, vinorelbine, eribulin, utidelone, carboplatin, sacituzumab govitecan, and trastuzumab deruxtecan (for HER2-low patients).

Drug: Organoid-guided treatment

Treatment of physician's choice

ACTIVE COMPARATOR

Subjects randomized to the treatment of physician's choice (TPC) group will receive physician-chosen therapy from the following options: taxane, anthracycline, 5-fluorouracil, gemcitabine, vinorelbine, eribulin, utidelone, carboplatin, sacituzumab govitecan, and trastuzumab deruxtecan (for HER2-low patients).

Drug: Taxane; Drug: Capecitabine; Drug: Gemcitabine; Drug: Vinorelbine; Drug: Eribulin; Drug: Anthracycline; Drug: Carboplatin; Drug: Utidelone; Drug: Trastuzumab deruxtecan; Drug: Sacituzumab govitecan

Interventions

Organoid-guided treatment DRUG

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).

Organoid-guided treatment

Taxane DRUG

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

Also known as: Abraxane, Lipusu

Treatment of physician's choice

Capecitabine DRUG

1000-1250mg/m2, PO, bid, days1-14, q3w

Also known as: Xeloda

Treatment of physician's choice

Gemcitabine DRUG

800-1200mg/m2, IV, days 1, 8, q3w

Also known as: Gemzar

Treatment of physician's choice

Vinorelbine DRUG

20-35mg/m2, IV, days 1 and 8, q3w

Also known as: Navelbine

Treatment of physician's choice

Eribulin DRUG

1.4mg/m2, IV, days 1 and 8, q3w

Also known as: Halaven

Treatment of physician's choice

Anthracycline DRUG

Liposomal doxorubicin 50mg/m2, IV, q3w OR Liposomal doxorubicin 40mg/m2+Cyclophosphamide 600mg/m2, IV, q3w

Also known as: Doxil, Lipodox

Treatment of physician's choice

Carboplatin DRUG

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

Also known as: Paraplatin

Treatment of physician's choice

Utidelone DRUG

30mg/m2, IV, once per day on days 1-5, q3w

Also known as: UTD1

Treatment of physician's choice

Trastuzumab deruxtecan DRUG

5.4mg/kg, IV, q3w

Also known as: Enhertu

Treatment of physician's choice

Sacituzumab govitecan DRUG

10mg/kg, IV, days 1 and 8, q3w

Also known as: Trodelvy

Treatment of physician's choice

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Men or women ≥18 years old.
• Pathologically documented unresectable locally advanced or metastatic breast cancer that:
• 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.
• 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.
• 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.
• Documented radiologic progression (during or after most recent treatment).
• Presence of at least 1 measurable lesion based on computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• All subjects must have a recent tumor sample after the most recent treatment regimen or agree to undergo a tissue biopsy prior to randomization.
• No visceral crisis.
• Life expectancy of ≥ 6 months as assessed by the treating investigator.
• Complete all required baseline laboratory tests and imaging examinations within 28 days before randomization.
• Normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
• 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.

You may not qualify if:

• 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.
• Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious.
• 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).
• Inflammatory breast cancer.
• Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
• Major surgery within 3 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
• Systemic treatment with anticancer therapy, antibody-based therapy, hormonal therapy, or radiotherapy within 3 weeks before study treatment.
• Participation in a therapeutic clinical study within 3 weeks before study treatment, or current participation in other investigational procedures.
• Has multiple primary malignancies within 3 years, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, or contralateral breast cancer.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
• 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.
• Has known human immunodeficiency virus infection or active hepatitis B or C infection.
• Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
• Has gastrointestinal disorders likely to interfere with absorption of the study medication.
• Is pregnant or breastfeeding or planning to become pregnant.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Sun Yat-sen University: collaborator
• Shantou Central Hospital: collaborator

Study Sites (1)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

RECRUITING

MeSH Terms

Interventions

taxane; Albumin-Bound Paclitaxel; Capecitabine; Gemcitabine; Vinorelbine; eribulin; Anthracyclines; liposomal doxorubicin; Carboplatin; trastuzumab deruxtecan; sacituzumab govitecan

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Coordination Complexes

Central Study Contacts

Kun Wang, M.D.

CONTACT

00862083827812; wangkun@gdph.org.cn

Hong-Fei Gao, M.D.

CONTACT

nfzj1988@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: October 22, 2023
• First Posted: October 26, 2023
• Study Start: October 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: November 25, 2024

Record last verified: 2024-11

Locations

CN (1)