Phase 1
N=23
PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery
Advanced Breast Carcinoma · Advanced Malignant Solid Neoplasm · Advanced Prostate Carcinoma · Anatomic Stage III Breast Cancer AJCC v8 · Anatomic Stage IIIA Breast Cancer AJCC v8
Bottom Line
View on ClinicalTrials.gov: NCT03218826 ↗Enrolled (actual)
23
Serious AEs
56.5%
Results posted
Sep 2023
Primary outcome: Primary: Number of Participants With Dose Limiting Toxicity (DLT) — 2; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Docetaxel (Drug); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); PI3Kbeta Inhibitor AZD8186 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jul 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicity (DLT) |
2; 0; 0; 0; 0; 3 | — |
| PRIMARY Number of Participants With Adverse Events (AEs) Grades 3-5 |
4; 1; 3; 1; 4; 1 | — |
| SECONDARY Objective Response Rate (ORR) |
0; 0; 1; 0; 0; 5 | — |
| SECONDARY Clinical Benefit Rate (CBR) Defined as Complete Response (CR), Partial Response (PR), or Stable Disease |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Maximum Blood Concentrations of Docetaxel When Also Taking AZD8186 |
3083.3; 2060.0; 3280.0; 3450.0; 6981.7; 3615.0 | — |
Summary
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 tumors with PTEN or PIK3CB mutations that have spread to other places in the body (metastatic) or cannot be removed by surgery. PI3Kbeta inhibitor AZD8186 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving PI3Kbeta inhibitor AZD8186 and docetaxel may work better in treating patients with solid tumors.
Eligibility Criteria
Inclusion Criteria
- 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
- Patients must be able to swallow and retain oral medications and be without gastrointestinal illnesses that would preclude absorption of AZD8186
- Unlimited prior therapies allowed
- Docetaxel appropriate
- Patients who have not received prior docetaxel (or other taxane therapy) in the advanced setting are eligible for all cohorts
- Patients who have previously received docetaxel (or other taxane therapy) in the advanced setting are eligible for the dose escalation cohort only, if anticipated to have maintained taxane sensitivity and in the opinion of the investigator would still benefit from further docetaxel therapy
- Eastern Cooperative Oncology Group (ECOG) performance status = = 60%)
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Hemoglobin >= 8 g/L
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = = 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- PTEN or PIK3CB mutated advanced solid tumor
- PTEN loss of function mutation or PIK3CB gain of function mutation identified by local Clinical Laboratory Improvement Act (CLIA) certified next generation sequencing (NGS)
- Breast cancers patients enrolled on this study must have either:
- Estrogen receptor positive and HER2 negative breast cancer
- Triple negative breast cancer
- Adequate archival tissue (metastatic tissue sample is preferable but primary tumor tissue will be acceptable) or willing to undergo pre-treatment biopsy (for central confirmation of molecular alteration and PTEN immunohistochemical assessment) if adequate archival tissue is unavailable
- The effects of AZD8186 on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of AZD8186 administration
- Ability to understand and the willingness to sign a written informed consent document
- DOSE ESCALATION COHORT: Prior receipt of docetaxel is permitted
- DOSE ESCALATION COHORT: Measurable disease is not required for enrollment
- PHARMACODYNAMIC EXPANSION COHORT: Prior receipt of docetaxel is not permitted
- PHARMACODYNAMIC EXPANSION COHORT: Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- PHARMACODYNAMIC EXPANSION COHORT: Consent to allow mandatory paired (pre- and on- treatment) fresh tissue biopsies if deemed safe to do so for quantitation of Akt pathway signaling proteins
- DISEASE SPECIFIC EXPANSION COHORTS: Prior receipt of docetaxel is not permitted
- DISEASE SPECIFIC EXPANSION COHORTS: Patients (excepting the prostate cancer patients) must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >
Data sourced from ClinicalTrials.gov (NCT03218826). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.