AZD8186 + Docetaxel for Advanced Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: HER2 positive, Brain metastases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 21-day cycles until April 30, 2022

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced or spreading solid tumors that have specific genetic changes (PTEN or PIK3CB mutations). The trial aims to determine the best dose and explore the side effects of combining AZD8186, an experimental drug that may inhibit tumor growth, with the chemotherapy drug docetaxel. This study suits those whose cancer cannot be surgically removed and who have not responded to other treatments. Participants must be able to take oral medication and have tumors with specific gene mutations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications that strongly affect CYP3A4 enzymes. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that patients with advanced solid tumors generally tolerate the combination of AZD8186 and docetaxel well. In one study, most side effects were manageable, though some patients experienced neutropenia, a decrease in white blood cells that can increase infection risk. The study effectively managed this side effect. While AZD8186 remains under investigation and lacks approval for any condition, docetaxel is an approved and widely used chemotherapy drug for other cancer types. This suggests some evidence of safety for the combination, but further research is necessary to fully understand its effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of AZD8186 with Docetaxel because it targets cancer in a unique way. Unlike standard treatments that often focus solely on halting cell division, AZD8186 is a PI3Kbeta inhibitor that specifically blocks a pathway crucial for cancer cell growth and survival. This dual approach not only aims to stop tumor growth but also hopes to overcome resistance to current therapies, potentially leading to more effective and longer-lasting results. By combining this new mechanism with the established efficacy of Docetaxel, there's an opportunity to enhance treatment outcomes for patients with advanced cancer.

What evidence suggests that AZD8186 + Docetaxel might be an effective treatment for advanced cancer?

This trial will evaluate the combination of AZD8186 with docetaxel for patients with advanced solid tumors that have specific genetic changes called PTEN or PIK3CB mutations. Research has shown that this combination might be beneficial. In one study with 18 patients, one person's tumor shrank significantly, a result known as a partial response. Docetaxel is already effective for treating advanced non-small cell lung cancer, suggesting it could work well in this combination too. AZD8186 blocks certain proteins that tumors need to grow, potentially slowing or stopping the cancer. Overall, this treatment combination is generally well tolerated, though some patients experienced manageable side effects like low white blood cell counts. ^{1 2 4 6 7}

Who Is on the Research Team?

Alison M Schram

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have specific mutations (PTEN or PIK3CB) and can't be removed by surgery or have spread. Participants must be able to take oral meds, have no major gastrointestinal issues affecting drug absorption, and agree to use contraception. Prior treatments are allowed; however, prior treatment with PI3K/AKT inhibitors or certain other conditions may disqualify a person.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and standard treatments are not effective.

You have enough white blood cells called neutrophils.

Your platelet count is at least 100,000 per microliter.

Exclusion Criteria

I have a bleeding condition or am at high risk for bleeding.

You are currently taking any other experimental medications.

My cancer has a RAF or PIK3CA mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive docetaxel IV over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 orally twice daily for 5 days each week. Cycles repeat every 21 days.

21-day cycles until April 30, 2022

1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days and then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• PI3Kbeta Inhibitor AZD8186

Trial Overview The trial is testing the combination of a new drug called AZD8186, which targets enzymes involved in tumor cell growth, with docetaxel, a chemotherapy drug. The goal is to find the safest dose and see if this combo works better than current treatments for these types of tumors.

How Is the Trial Designed?

Group I: Treatment (docetaxel, PI3Kbeta inhibitor AZD8186) Experimental Treatment 4 Interventions

Patients receive docetaxel IV over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 PO BID for 5 days each week. Cycles repeat every 21 days until April 30, 2022 in the absence of disease progression or unacceptable toxicity.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Docetaxel is an effective treatment for non-small cell lung cancer (NSCLC), showing comparable efficacy to newer platinum-based therapies in advanced stages, and has been approved for use in this context.

Clinical trials are ongoing to explore the best ways to combine docetaxel with other treatments, such as thoracic radiotherapy and molecularly targeted agents, to enhance its effectiveness in various stages of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. Davies, AM., Lara, PN., Mack, PC., et al.[2019]

In a Phase Ib study involving 19 patients with advanced solid tumors, the combination of alpelisib (a PI3K p110α inhibitor) and paclitaxel was assessed for safety and maximum tolerated dose, revealing that the maximum tolerated dose of alpelisib was 150 mg per day.

The treatment showed a challenging safety profile, with significant adverse effects including high rates of hyperglycemia (57.9%) and diarrhea (73.7%), leading to the decision not to proceed with the planned dose-expansion phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors. Rodon, J., Curigliano, G., Delord, JP., et al.[2019]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing survival benefits in both first- and second-line therapy, and is comparable or superior to other platinum-based chemotherapy options.

The drug has a manageable toxicity profile and has shown promising results when combined with novel targeted agents in Phase II studies, indicating its versatility in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. Wakelee, H., Ramalingam, S., Belani, CP.[2018]

Docetaxel, an anti-microtubule agent, has demonstrated significant effectiveness in treating metastatic breast cancer, as confirmed by Phase I and II trials.

However, this case report highlights a rare but serious side effect: a rapid onset of diffuse scleroderma-like illness in a patient undergoing treatment, emphasizing the need for monitoring adverse reactions during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scleroderma in association with the use of docetaxel (taxotere) for breast cancer. Hassett, G., Harnett, P., Manolios, N.[2018]

Docetaxel shows significant efficacy in treating advanced non-small cell lung cancer, with a 30% partial response rate in chemotherapy-naive patients and 20% in those who had previously failed platinum-based treatments, based on six phase II studies involving 268 patients.

The primary side effect of docetaxel is neutropenia, while fluid retention is common but usually manageable with corticosteroids, indicating that the treatment has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. Fossella, FV., Lee, JS., Berille, J., et al.[2018]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(25)01438-3/fulltext

A phase I study of AZD8186 in combination with docetaxel ... Of the 18 efficacy-assessable patients, 1 patient had a PR (ORR 5.6%, 90% CI 0.3% to 23.8%) (Figure 2). The PR was in a patient in DL −1b with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03218826

PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating ... To assess the safety and tolerability of AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40939237/

A phase I study of AZD8186 in combination with docetaxel ... The combination of AZD8186 and docetaxel was generally well tolerated, with the exception of neutropenia, which was effectively managed with ...

4. clinicaltrial.be clinicaltrial.be/en/details/8641?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Pati... To assess the clinical benefit rate at 24 weeks of AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB ...

5. withpower.com withpower.com/trial/phase-1-carcinoma-2-2018-0b78f

AZD8186 + Docetaxel for Advanced Cancer Docetaxel is an effective treatment for non-small cell lung cancer (NSCLC), showing comparable efficacy to newer platinum-based therapies in advanced stages, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03218826

NCT03218826 | PI3Kbeta Inhibitor AZD8186 and ... To assess the safety and tolerability of AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors.

7. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.IDNCI10131.html

NCI10131: A Phase 1 Study of AZD8186 in Combination ... This phase I trial studies the side effects and best dose of PI3Kbeta inhibitor AZD8186 when given together with docetaxel in treating patients with solid ...