Chiauranib for Advanced Cancers

(SCLC Trial)

Recruiting at 10 trial locations

Overseen By Liz Wieland

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Chipscreen Biosciences, Ltd.

Must not be taking: Corticosteroids, Strong CYP3A4 inhibitors

Disqualifiers: Cardiovascular diseases, Hypertension, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 6 months

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called chiauranib, a potential new drug, for individuals with advanced cancers unresponsive to standard treatments. The goal is to determine the best dose and evaluate how chiauranib might control cancer growth over 28-day cycles. Participants will receive one of three doses to identify the most effective and safe amount. This trial suits individuals diagnosed with advanced solid tumors, such as lung, colorectal, or ovarian cancer, that have not improved with existing therapies. As a Phase 1 trial, the research focuses on understanding how chiauranib works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anticancer therapy at least 21 days before joining. If you are on strong CYP3A4 inhibitor or inducer drugs, you will need to stop those as well during the dose escalation stage. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that chiauranib has been tested in earlier studies for safety in humans. In one study, researchers administered chiauranib to patients with advanced solid tumors to assess tolerance. The results indicated that a 50 mg dose taken once daily was safe and tolerable.

Another study tested various doses of chiauranib to understand its metabolism in the body. The findings revealed that the treatment was generally well-tolerated and did not cause serious side effects at the recommended dose. Some patients experienced mild to moderate side effects, but these were manageable.

Overall, previous research supports that chiauranib is well-tolerated in humans at the recommended dose levels. While minor side effects may occur, they are usually not serious. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Chiauranib stands out because it offers a potentially new approach to treating advanced cancers. While most cancer treatments, like chemotherapy and targeted therapies, attack rapidly dividing cells or specific cancer cell targets, Chiauranib works differently by simultaneously inhibiting angiogenesis (the formation of new blood vessels that feed tumors), controlling cancer cell growth, and modulating the immune response. This multi-target mechanism could lead to more comprehensive cancer control, which is why researchers are excited about its potential to offer improved outcomes for patients with advanced cancers compared to current options.

What evidence suggests that chiauranib might be an effective treatment for advanced cancers?

Research has shown that chiauranib may help treat advanced cancers. In early studies, researchers administered chiauranib to patients with advanced solid tumors to assess its safety and effectiveness. Patients tolerated the treatment, and there were indications it could help stop tumor growth. Laboratory tests conducted before human trials demonstrated that chiauranib can combat cancer cells in various advanced cancers. Although further research is necessary to confirm these findings, the initial results are promising for its potential use in cancer treatment. ^{2 4 6 7 8}

Who Is on the Research Team?

Cabilia Pichardo, MD

Principal Investigator

Executive Director of Clinical Development

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or relapsed/refractory Small Cell Lung Cancer (SCLC) who have measurable disease progression. Participants must be in good physical condition (ECOG 0-1), have proper organ function, and a life expectancy that allows participation. Women of childbearing age and men must agree to use effective contraception during the study and for some time after.

Inclusion Criteria

Patient is able to provide voluntary informed consent

I have a tumor that can be measured and has grown after treatment.

I can and will use effective birth control during and for 12 weeks after the study.

Exclusion Criteria

I have a history of cancer.

I must continue taking certain medications during the study.

You currently have problems with using drugs or alcohol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Participants undergo dose-escalation with chiauranib in 3 cohorts (35 mg, 50 mg, 65 mg) to determine the maximum tolerated dose and recommended Phase 2 dose.

34 days

Multiple visits for dose escalation and monitoring

Treatment

Participants receive the recommended Phase 2 dose of chiauranib once daily in 28-day cycles continuously with no interruption.

6 months

Visits on days 1, 14, 28 during Cycle 1; day 28 in Cycle 2 and all subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and survival outcomes.

30 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Chiauranib

Trial Overview The trial is testing Chiauranib, an investigational drug, in two stages: Phase 1b determines the safe dosage through dose escalation, while Phase 2 administers this determined dose daily over continuous 28-day cycles without breaks to evaluate its effectiveness against cancer.

How Is the Trial Designed?

Group I: Study arm (65 mg) Experimental Treatment 1 Intervention

Phase 1b: Patients will be enrolled sequentially in 3 dose-escalating cohorts (Chiauranib capsules 35, 50, and 65 mg, orally)

Group II: Study arm (50 mg) Experimental Treatment 1 Intervention

Phase 1b: Patients will be enrolled sequentially in 3 dose-escalating cohorts (Chiauranib capsules 35, 50, and 65 mg, orally)

Group III: Study arm (35 mg) Experimental Treatment 1 Intervention

Phase 1b: Patients will be enrolled sequentially in 3 dose-escalating cohorts (Chiauranib capsules 35, 50, and 65 mg, orally)

Who Is Running the Clinical Trial?

Chipscreen Biosciences, Ltd.

Lead Sponsor

Trials

39

Recruited

5,300+

Published Research Related to This Trial

In a study of 385 patients with various solid tumors, only 38 had tumors with the targeted EGFR/HER2 gene amplification, and 20 were treated with afatinib, resulting in a low objective response rate of 5%, indicating limited efficacy as a single-agent treatment.

Despite the low response rate, afatinib showed some potential with one complete response and stable disease in eight patients, highlighting the challenges of using a biomarker-driven approach for patient selection in diverse tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. Kwak, EL., Shapiro, GI., Cohen, SM., et al.[2018]

Cediranib, a potent inhibitor of vascular endothelial growth factor signaling, was found to be generally well tolerated at doses of 30 mg/day or less in Japanese patients with advanced solid tumors, with the maximum tolerated dose identified as 30 mg/day due to dose-limiting toxicities at higher doses.

In terms of efficacy, out of 32 evaluable patients, two experienced partial responses and 24 maintained stable disease for at least 8 weeks, indicating promising antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors. Yamamoto, N., Tamura, T., Yamamoto, N., et al.[2022]

Chiauranib, a novel multitarget inhibitor, shows significant promise in treating transformed follicular lymphoma (t-FL) by inhibiting tumor growth, migration, and promoting apoptosis in both cell lines and a xenograft model.

The mechanism of action involves suppression of VEGFR2 phosphorylation, which disrupts the MEK/ERK/STAT3 signaling pathway, leading to effective anti-t-FL effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Studies of Chiauranib Show It Inhibits Transformed Follicular Lymphoma through the VEGFR2/ERK/STAT3 Signaling Pathway. Tang, Y., Zhong, M., Pan, G., et al.[2023]

The maximum tolerated dose (MTD) of afatinib combined with paclitaxel was determined to be 40mg of afatinib with 80mg/m² of paclitaxel, showing manageable adverse effects such as diarrhea and fatigue in a study of 16 patients.

The combination treatment demonstrated promising antitumor activity, with 31% of patients achieving confirmed partial responses, particularly in non-small cell lung cancer, and half of the patients remaining on the study for at least 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of daily afatinib, an irreversible ErbB family blocker, in combination with weekly paclitaxel in patients with advanced solid tumours. Suder, A., Ang, JE., Kyle, F., et al.[2018]

Chiauranib, a multi-target inhibitor, was found to have an acceptable safety profile in a phase I study with 18 patients, with the maximum tolerated dose identified as 50 mg/day due to dose-limiting toxicity like grade 3 hypertension.

While no complete or partial responses were observed, 66.7% of patients achieved stable disease, indicating potential antitumor activity that warrants further investigation in upcoming phase Ib/II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of chiauranib, a novel angiogenic, mitotic, and chronic inflammation inhibitor, in patients with advanced solid tumors. Sun, Y., Yang, L., Hao, X., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11312147/

Efficacy and safety of chiauranib in a combination therapy in ... In its first-in-human clinical trial, chiauranib was administered to 18 patients with advanced solid tumors to determine the tolerability and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02122809

NCT02122809 | Phase I Study of Chiauranib in Patients ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05271292?term=NCT03216343%20NCT04830813%20NCT05271292&rank=1

NCT05271292 | Chiauranib for Advanced Solid Malignant ... This is a Phase 1b/2, single-arm, open-label, dose-escalation study including 2 stages: Phase 1b: Dose-Escalation Stage (Single-Dose and Consecutive-Dose ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S001429991930202X

CS2164 suppresses acute myeloid leukemia cell growth ... Amazing results obtained from the preclinical study demonstrated that CS2164 has anti-tumor activity across a broad range of advanced cancers ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39123210/

Efficacy and safety of chiauranib in a combination therapy ... Efficacy and safety of chiauranib in a combination therapy in platinum-resistant or refractory ovarian cancer: a multicenter, open-label, phase ...

6. medchemexpress.com medchemexpress.com/chiauranib.html?srsltid=AfmBOooi86wxIu10bnDRu5snM0b4FMq67SUBN1Lue7Pp3i_fiLBBPeZZ

Chiauranib (Ibcasertib) | Multi-target Inhibitor Chiauranib (CS2164) is an orally active multi-target inhibitor against tumor angiogenesis. Chiauranib potently inhibits the angiogenesis-related kinases ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6332596/

Phase I dose-escalation study of chiauranib, a novel ... Based on the safety data, 50 mg chiauranib administered orally once daily was considered to be both the MTD and the RP2D. Safety and adverse ...

8. molecular-cancer.biomedcentral.com molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-02076-x

Efficacy and safety of chiauranib in a combination therapy in ... In its first-in-human clinical trial, chiauranib was administered to 18 patients with advanced solid tumors to determine the tolerability and ...