AZD8186 + Docetaxel for Advanced Cancer

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

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug (AZD8186) combined with chemotherapy (docetaxel) in patients with advanced solid tumors with specific genetic mutations. The new drug aims to block enzymes needed for cancer growth, while the chemotherapy helps kill or stop the spread of cancer cells. AZD8186 has shown enhanced efficacy when combined with other treatments.

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.

What data supports the effectiveness of the drug AZD8186 + Docetaxel for advanced cancer?

Research shows that combining docetaxel with PI3K inhibitors, like GDC-0941 and PX-866, enhances the effectiveness of docetaxel in treating cancers such as breast cancer and non-small cell lung cancer by increasing cancer cell death. This suggests that AZD8186, a similar PI3K inhibitor, might also improve the effectiveness of docetaxel in advanced cancer. ^{1 2 3 4 5}

What safety information is available for the combination of AZD8186 and Docetaxel in treating advanced cancer?

Docetaxel, also known as Taxotere, has been associated with side effects like neutropenia (low white blood cell count), alopecia (hair loss), skin reactions, and fluid retention. In some cases, it has also been linked to a scleroderma-like illness (a condition causing hardening and tightening of the skin). ^{2 3 6 7 8}

What makes the drug AZD8186 + Docetaxel unique for advanced cancer treatment?

The combination of AZD8186, a PI3Kbeta inhibitor, with Docetaxel is unique because it targets the PI3K pathway, which is involved in cancer cell growth and survival, potentially enhancing the effectiveness of Docetaxel, a standard chemotherapy drug, by increasing cancer cell death. ^{1 2 3 5 9}

Research Team

Alison M Schram

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours. [2021]

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

GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of docetaxel in human breast cancer models by increasing cell death in vitro and in vivo. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. [2018]

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

A randomized, phase 2 trial of Docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic non-small-cell lung cancer. [2020]

6. United States 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. [2018]

7. Italy pubmed.ncbi.nlm.nih.gov

Scleroderma in association with the use of docetaxel (taxotere) for breast cancer. [2018]

8. United States 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. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Synergistic effect of the γ-secretase inhibitor PF-03084014 and docetaxel in breast cancer models. [2023]