Study of ACE-86225106 to Treat Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase I/II, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of ACE-86225106 as Monotherapy in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06380660
• Other study ID #: ACE-106-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 22, 2024
• Est. completion date: March 21, 2029

Study information

• Verified date: April 2024
• Source: Acerand Therapeutics Limited
• Contact: Teresa Shi
• Phone: 8613916513539
• Email: teresa.shi[@]acerand.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if the experimental treatment with poly-ADP ribose polymerase (PARP) inhibitor, ACE-86225106 is safe, tolerable and has anti-cancer activity in adult patients with advanced solid tumors.

Description:

This study is a Phase I/II, open-label, multicentre study of ACE-86225106 administered orally in patients with advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 298
• Est. completion date: March 21, 2029
• Est. primary completion date: December 21, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provide written informed consent;

2. Advanced solid tumors, difficult to treat or intolerant to standard treatment, suitable for investigational treatment;

3. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

4. Has a life expectancy of at least 3 months.

5. Has measurable disease per RECIST 1.1, castration-resistant prostate Ccancer (CRPC) patients can be assessed according to PCWG3;

6. Adequate organ function and bone marrow function;

7. Can provide tumor specimens and blood samples for Homologous Recombination Deficiency (HRD)/(Breast Cancer gene) BRCA gene testing.

Exclusion Criteria:

1. Receiving any anti-cancer drugs, major surgery, extensive radiation therapy, or local radiation therapy within protocol-defined wash-out period;

2. Concomitant use of medications or herbal supplements known to be strong or moderate inhibitors or inducers of cytochrome P450 3A4 (CYP3A4);

3. Receiving continuous corticosteroid treatment with a dose of prednisone greater than 10 mg/day or an equivalent dose.

4. Receiving continuous treatment with prednisone at a dose of >10 mg/d or other corticosteroids at an equivalent dose for any reason.

5. Any previous treatment-related toxicities have not recovered, i.e., to = Grade 1 (as evaluated by NCI-CTCAE v5), except alopecia and other Grade 2 toxicities that are deemed not to affect the conduct of the study, as assessed by the sponsor and the clinical investigator.

6. Spinal cord compression or brain metastases unless asymptomatic, treated and stable.

7. Severe cardiovascular disorders.

8. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with evidence suggesting possible MDS/AML.

9. Concomitant diseases or conditions that would preclude the absorption of the investigational product.

10. Active infections, or a known history of HIV infection, or a known active hepatitis B or C, or a known active tuberculosis.

11. Other malignancies that require treatment within 3 years prior to first dose of study investigational product.

12. Conditions with rapid deterioration during the screening period.

13. Known allergy or hypersensitivity to the investigational product or any of the excipients of the investigational product.

14. Has other medical conditions that at the discretion of investigator interfere with safety or efficacy evaluation, or affect treatment compliance.

Related Conditions & MeSH terms

• BRCA1 Mutation
• BRCA2 Mutation
• Breast Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Prostate Cancer
• Solid Tumor, Adult

Intervention

Drug:
• ACE-86225106 tablet
ACE-86225106 will be administered orally daily as a continuous regimen. Subjects will continue to receive study treatment until PD as judged by local investigator review, development of unacceptable toxicity, or withdrawal of consent.

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Acerand Therapeutics (Shanghai) Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants experiencing adverse events (AEs)/serious adverse events (SAEs)	Number of participants with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination, etc.	From time of information consent to 30 days post last dose, up to 3 years
Primary	The number of patients experiencing dose limiting toxicity (DLT), as defined in the protocol	A DLT is defined as any toxicity events related to ACE-86225106 that occur from the first dose of study treatment until the planned end date of Cycle 1 (DLT assessment period), meeting the criteria specified in protocol.	From the first dose of ACE-86225106 on Cycle 1 Day 1 up to and including the planned end of Cycle 1 (at the end of 28 days)
Primary	Recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD)	RP2D will be finally determined by the Safety Monitoring Committee (SMC) and sponsor based on all data from the dose escalation module and backfill module, as well as the exposure-response relationship evaluated (if available). MTD is defined as the maximum dose level at which =1 patient have DLTs during the DLT observation period, and it should be determined with 6 evaluable patients.	Up to 3 years
Secondary	Objective Response Rate (ORR)	ORR is defined as proportion of patients who achieved complete response (CR) or partial response (PR) according to RECIST 1.1 recorded from first investigational product treatment until disease progression or death due to any cause. The confirmation of response for patients who has PR or CR at first time should be performed by at least 4 weeks. For castration-resistant prostate cancer (CRPC) patients, bone lesion will be assessed according to PCWG3 criteria.	Up to 3 years
Secondary	Duration of Response (DoR) and Time to Response (TTR)	DOR is defined, for patients with an objective response, as the time from first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause.	Up to 3 years
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from the first study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause.	Up to 3 years
Secondary	Overall Survival (OS)	OS is defined as the time from the first study treatment to the date of death due to any cause	Up to 3 years
Secondary	Pharmacokinetic (PK) parameters and Pharmacodynamic (PD) marker change	Blood drug concentrations at each scheduled time point will be summarized descriptively, and individual and mean concentration-time curves will be plotted by dose group.	Up to 3 years
Secondary	Serum tumor marker change: CA125, etc. (OC), prostatic specific antigen (PSA, prostate cancer) decreased, and specific tumor markers for other tumor types may also be included (to be assessed by clinical investigators)	The tests for the above serum tumor markers will support the tumor response evaluation.	Up to 3 years