Evaluating the safety and effectiveness of utidelone capsules in patients with advanced solid tumors

Phase I Clinical Trial on Tolerability and Bioavailability of Utidelone Capsule in Patients With Advanced Solid Tumors

This study is testing if utidelone capsules are safe and effective for people with advanced solid tumors, including those with metastatic breast cancer, by comparing them to injections and seeing how food affects their absorption.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Beijing Biostar Pharmaceuticals Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT05700084 on ClinicalTrials.gov

What this trial studies

This clinical trial consists of three parts aimed at assessing the tolerability and bioavailability of utidelone capsules in patients with advanced solid tumors. The first part is a dose-escalation trial to determine the maximum tolerated dose and dose-limiting toxicity. The second part involves a pharmacokinetic comparison of utidelone capsules and injections, including the effect of food on absorption. The third part extends the trial to evaluate the combination of utidelone capsules with capecitabine specifically in patients with advanced metastatic breast cancer.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 70 with advanced solid tumors or advanced metastatic breast cancer.

Not a fit: Patients with early-stage tumors or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors, potentially improving their outcomes.

How similar studies have performed: Other studies have shown promise in evaluating similar drug combinations, but this specific approach with utidelone is novel.

Eligibility criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be enrolled into the study:

1. Patients who have fully understood the objectives, content, process of the study and possible adverse events, voluntarily serves as a subject and signs the informed consent form.
2. Part 1 and Part 2: Patients with definitive histopathological diagnosis of advanced solid tumors. Part 3: Patients were diagnosed with advanced metastatic breast cancer by pathology and/or cytology.
3. Part 1 and Part 2: Male or female subjects aged ≥18 and ≤65, Part 3: Male or female subjects aged ≥18 and ≤70, with ECOG performance status scored 0-1.
4. Expected survival time ≥ 12 weeks;
5. At least one measurable lesion present according to RECIST 1.1 criteria.
6. Baseline routine blood tests within 1 week prior to enrollment is normal (not received blood transfusions or hematopoietic-stimulating factors within 14 days), with CTCAE grade ≤1 (based on normal values at each site's laboratory): a) Neutrophil count (ANC) ≥ 1.5 × 109/L; b) platelet count (PLT ) ≥ 100 × 109/L; c) Hemoglobin ≥9.0 g/dL.
7. Liver and kidney function test results are normal within 1 week prior to enrollment, with CTCAE grade ≤1 (based on normal values at each site's laboratory): a) Total bilirubin (TBIL) ≤ 1.5× the upper limit of normal value (ULN); b) Serum Glutamic Pyruvic Transaminase/Alanine Aminotransferease (SGPT /ALT) ≤ 2.5× ULN (Part 3 allowed ≤5×ULN in patients with liver metastases); c) Serum Glutamic-oxaloacetic Transaminase/Aspartate Aminotransferase (SGOT /AST) ≤ 2.5× ULN (Part 3 allowed ≤5×ULN in patients with liver metastases); d) Creatinine clearance (Ccr) ≥60 ml/min.
8. Patients with no functional disorders of major organs.
9. Fertile males and females of childbearing potential must agree to use effective contraception (so do their partners, using hormonal or barrier contraception, or abstinence) during the study and within at least 12 weeks after the last dose. The blood or urine pregnancy test for female patients of childbearing potential prior to enrollment must be negative.
10. Part 3: breast cancer patients who had received ≤4 previous chemotherapy regimens (adjuvant chemotherapy/neoadjuvant chemotherapy was considered as one chemotherapy regimen);
11. Part 3: history of prior treatment with at least one anthracycline or one taxane as neoadjuvant/adjuvant or advance therapy or both.

Exclusion Criteria:

Subjects who fulfill any one of the following exclusion criteria will be excluded from the study:

1. Patients who have received non-investigational anti-tumor therapies (such as chemotherapy, radiotherapy, immunotherapy, biological therapy or traditional Chinese medicine treatment) within 2 weeks prior to study drug administration.
2. Subjects with severe hypersensitivity to castor oil (this criteria is applicable to Part 2 of the study), and subjects who had hypersensitivity reaction caused by previous anti-microtubule drugs.
3. Patients with uncontrollable brain metastases (brain metastatic lesion confirmed by examination within 2 months after radiotherapy or other localized treatment); patients with uncontrollable bone metastases (patients who have had fracture or have the risk of fracture in recent days, patients who need surgery or localized radiotherapy in recent days, patients with other critical conditions)
4. Patients with serious comorbidities, such as severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, severe infections, active peptic ulcers, etc.
5. Patients with mental illnesses which are hard to control, patients who lack legal capacity or have limited legal capacity.
6. Patients with gastrointestinal diseases such as esophageal obstruction, pyloric obstruction, intestinal obstruction, or who are post-operative of gastrointestinal resection, or who have difficulty in swallowing due to other factors, interfering with oral administration and absorption of the drug.
7. Patients with active hepatitis B infections.
8. Patients with peripheral neuropathy grade\>1 within 4 weeks prior to enrollment (NCI CTCAE 5.0).
9. Patients who still experience ≥ Grade 2 acute toxicities caused by previous anti-tumor therapies (e.g. chemotherapy, radiotherapy, immunotherapy, biological therapy or TCM treatment) prior to enrollment (NCI-CTCAE 5.0, except alopecia).
10. Patients who have undergone any major surgery or have major trauma within 4 weeks prior to administration of the investigational product or are expected to undergo major surgery during the treatment.
11. Patients who have participated in another clinical trial or have received other investigational treatments within 4 weeks prior to administration of the investigational product.
12. Patients who, in the opinion of the investigator, are not suitable to participate in this study.
13. Part 3: other malignant tumors within 5 years before enrollment, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma, thyroid papillary carcinoma;
14. Part 3: previous or current capecitabine therapy (except if capecitabine was used in neoadjuvant/adjuvant therapy and progression occurred \> 12 months after completion of treatment, inclusion was allowed);
15. Part 3: patients with previous fluorouracil medication history with severe allergy or known dihydropyrimidine dehydrogenase (DPD) deficiency;
16. Part 3: previous or current use of utidelone (including utidelone injection and utidelone capsule); 17) Part 3: pregnant or lactating patients; 18) Part 3: uncontrolled pleural effusion, pericardial effusion or ascites (drainage once a month or more); 19) Part 3: a history of immunodeficiency, including positive HIV antibody test, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.

Where this trial is running

Beijing

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Binghe Xu, MD, PhD — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Study coordinator: RONGGUO QIU, PhD

Conditions Advanced Solid Tumor; Tolerability; Bioavailability