Chiauranib for Advanced Cancers

(SCLC Trial)

Recruiting in Palo Alto (17 mi)

+10 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Chipscreen Biosciences, Ltd.

Must not be taking: Corticosteroids, Strong CYP3A4 inhibitors

Disqualifiers: Cardiovascular diseases, Hypertension, CNS metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called chiauranib for patients with advanced cancers that don't respond to standard treatments. It aims to block the signals that cancer cells need to grow. The focus is on patients with small cell lung cancer that has worsened after previous treatments.

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.

What makes the drug Chiauranib unique for treating advanced cancers?

Chiauranib is unique because it is an oral drug that targets multiple pathways involved in cancer growth, including those related to blood vessel formation (angiogenesis), cell division (mitosis), and inflammation. This multi-target approach, particularly its inhibition of VEGFR2 and the ERK/STAT3 signaling pathway, makes it a promising option for cancers with no efficient treatment strategies, like transformed follicular lymphoma. ^{1 2 3 4 5}

Research Team

Cabilia Pichardo, MD

Principal Investigator

Executive Director of Clinical Development

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Chiauranib (Tyrosine Kinase Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Germany 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Preclinical Studies of Chiauranib Show It Inhibits Transformed Follicular Lymphoma through the VEGFR2/ERK/STAT3 Signaling Pathway. [2023]

3. England 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. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. [2018]

5. England 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. [2020]