What side effects are associated with this type of intervention?

Common cancer treatments, such as PI3K inhibitors and chemotherapy agents like Docetaxel, have a range of known side effects. PI3K inhibitors can cause hyperglycemia, rash, diarrhea, and liver enzyme abnormalities. Chemotherapy agents like Docetaxel are associated with neutropenia, anemia, fatigue, hair loss, nausea, vomiting, peripheral neuropathy, and increased risk of infection. These side effects necessitate careful monitoring and management to maintain patient quality of life.

What prior FDA approvals exist?

The FDA has approved several drugs targeting the PI3K pathway, such as Alpelisib (PIQRAY), which inhibits PI3K-alpha and is used in combination with fulvestrant for HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer. Additionally, Idelalisib (ZYDELIG) targets PI3K-delta and is approved for certain types of blood cancers. Chemotherapy agents like Docetaxel (TAXOTERE) are widely used in various cancers, including breast, non-small cell lung, prostate, and gastric cancers, due to their ability to kill tumor cells, inhibit their division, and prevent their spread. Combining PI3K inhibitors with chemotherapy agents like Docetaxel aims to enhance treatment efficacy by simultaneously targeting different mechanisms of tumor growth and survival.

What other types of research exist?

Promising alternatives include: 1) Bortezomib, which inhibits proteasome activity and has shown efficacy in combination with taxanes like docetaxel in prostate cancer. 2) HDAC6-selective inhibitors, which enhance the anticancer effects of paclitaxel in ovarian cancer by increasing pro-apoptotic markers and decreasing anti-apoptotic markers. 3) MEK inhibitors such as pimasertib and refametinib, which are in clinical development and have shown potential in improving progression-free survival. 4) Chk1 inhibitor PF-00477736, which enhances the efficacy of docetaxel by abrogating mitotic and DNA damage checkpoints.

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Mitotic Inhibitor

AZD8186 + Docetaxel for Advanced Cancer

Phase 1

Waitlist Available

Led By Alison M Schram

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective

PTEN loss of function mutation or PIK3CB gain of function mutation identified by local Clinical Laboratory Improvement Act (CLIA) certified next generation sequencing (NGS)

Must not have

Existing bleeding or condition associated with increased risk of bleeding

Any known concurrent RAF or PIK3CA mutation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to blocking enzymes needed for cell growth which could affect normal cells as well as cancer cells. Chemotherapy like docetaxel can cause hair loss, nausea, fatigue, low blood counts leading to increased infection risk and bleeding problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My cancer has a specific genetic change detected by a certified test.

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My breast cancer is either estrogen receptor positive and HER2 negative, or it is triple negative.

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I have never received docetaxel treatment.

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I can swallow pills and don’t have stomach issues affecting medicine absorption.

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My kidney function, measured by creatinine or its clearance, is within the normal range.

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My advanced cancer has a PTEN or PIK3CB mutation.

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I have a tumor that can be measured and is big enough according to specific guidelines.

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I have never been treated with docetaxel.

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I have a tumor that can be measured and is larger than 1 cm.

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I have advanced prostate cancer resistant to standard treatments.

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I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My cancer has a RAF or PIK3CA mutation.

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I do not have any severe illnesses that my doctors are still trying to get under control.

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I am not pregnant or breastfeeding.

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My breast cancer is HER2 positive.

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I have been treated with PI3K/AKT inhibitors before.

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I have recovered from side effects of previous cancer treatments.

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I have had severe allergic reactions to similar cancer drugs or to docetaxel.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With Adverse Events (AEs) Grades 3-5

Number of Participants With Dose Limiting Toxicity (DLT)

Secondary study objectives

Clinical Benefit Rate (CBR) Defined as Complete Response (CR), Partial Response (PR), or Stable Disease

Maximum Blood Concentrations of Docetaxel When Also Taking AZD8186

Objective Response Rate (ORR)

Other study objectives

Co-mutated genes in PTEN or PIK3CB mutated tumors

Isoform-specific AKT inhibition

Ovulation Inhibition

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (docetaxel, PI3Kbeta inhibitor AZD8186)Experimental Treatment4 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Docetaxel

1995

Completed Phase 4

~6550

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Cancer treatments generally fall into two categories: targeted therapies and chemotherapy. Targeted therapies, like the PI3Kbeta inhibitor AZD8186, inhibit specific enzymes or pathways crucial for tumor cell growth, offering a more precise attack on cancer cells with fewer side effects on normal cells. Chemotherapy agents, such as Docetaxel, kill rapidly dividing cells, halt their division, or prevent their spread, but they can also affect healthy cells, leading to broader side effects. Understanding these mechanisms helps cancer patients and their doctors make informed decisions about treatment options, balancing effectiveness with potential side effects.

Informed Consent and Decision Making Among Participants in Novel-Design Phase I Oncology Trials.A novel PI3K inhibitor PIK-C98 displays potent preclinical activity against multiple myeloma.