Galunisertib and Paclitaxel in Treating Patients With Metastatic Androgen Receptor Negative (AR-) Triple Negative Breast Cancer

NCT02672475 | Completed Phase 1 DMC

• 4 other identifiers: VICC BRE 1557NCI-2015-02055H9H-MC-E005P30CA068485
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of Galunisertib when given together with paclitaxel in treating patients with androgen receptor negative or triple negative breast cancer that has spread to other places in the body. Some tumors need growth factors, which are made by the body's white blood cells, to keep growing. Galunisertib may interfere with growth factors and help cause tumor cells to die. Drugs used in chemotherapy, such as paclitaxel, 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 Galunisertib together with paclitaxel may kill more tumor cells.

Conditions

Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Adverse events will be classified by type, incidence, severity and causality. All adverse events will be summarized by patient and dose level.of galunisertib in combination with paclitaxel graded by National Cancer Institute Common Terminology Criteria For Adverse Events (NCI CTCAE) version 4.03

  Up to 28 days after last dose of study treatment

• Maximum Tolerated Dose (MTD) of paclitaxel + LY2157299

  MTD is defined as the highest dose tested in which a dose limiting toxicity is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels galunisertib in combination with paclitaxel graded by NCI CTCAE version 4.03

  Up to 28 days

Secondary Outcomes (2)

• Overall Response Rate (ORR)

  On-treatment date to date of disease progression, assessed up to 3 years

• Progression-Free Survival (PFS)

  On-study date to lesser of date of progression or date of death from any cause, assessed up to 3 years

Study Arms (1)

Treatment (Paclitaxel, Galunisertib)

EXPERIMENTAL

Patients receive Paclitaxel IV on days 1, 8, and 15. Patients also receive GalunisertibPO BID on days 1-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Galunisertib; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

Interventions

Galunisertib DRUG

Given PO

Also known as: LY-2157299, LY2157299

Treatment (Paclitaxel, Galunisertib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Paclitaxel, Galunisertib)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (Paclitaxel, Galunisertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must provide informed written consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Clinical stage IV invasive mammary carcinoma that is ER, PR, HER2 negative (triple negative) previously documented by conventional methods (IHC, FISH). ER negative is defined as expression of ER in \<1% cells, PR negative is defined as expression of PR in \<1% cells, HER2 negative \[acceptable methods of HER2 analysis include IHC (0, 1+), fluorescence in situ hybridization (FISH) with HER2/CEN-17 ratio \<2, and/or chromogenic in situ hybridization (CISH) with HER2/CEN-17 ratio \<2\], as previously documented by histological analysis.
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
• Patients must have available tissue (archived formalin-fixed paraffin embedded blocks \[FFPB\] or fresh frozen tissue from original diagnosis or metastatic setting) for correlative studies; patients will not be able to start study drugs without tumor tissue availability; patients without available tumor tissue can still participate if willing to have a fresh biopsy of a metastatic lesion that is deemed to be medically safe (except for bone metastases)
• Any number of prior therapies as long as patients have adequate performance status and meet all other eligibility criteria.
• Patients must have adequate hematologic, hepatic, and renal function. All laboratory tests must be obtained less than 21 days from study entry. These include:
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \>= 9 g/dL
• Creatinine =\< 1.5 X upper limits of normal
• International normalized ratio (INR) =\< 2
• Total serum bilirubin =\< 1.5 x upper limit of normal (ULN) unless attributable to Gilbert's syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN (or =\< 4.0 x ULN if hepatic metastases are present)
• Patients must be able to swallow and retain oral medication

You may not qualify if:

• Locally recurrent resectable breast cancer
• Known androgen receptor (AR) positive breast cancer (AR staining \> 10% by immunohistochemistry is considered positive). If the AR status is unknown, the patient can go on study.
• Pregnant or lactating women
• Patients with untreated or symptomatic metastatic central nervous system (CNS) disease; however patients with CNS involvement may participate if:
• Clinically stable with respect to the CNS tumor at the time of screening and \> 2 weeks from prior therapy completion (including radiation and/or surgery) to the start of study treatment
• Not on steroid therapy
• Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases (these include carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate, and vigabatrin)
• Patient has a history of another malignancy within 2 years prior to starting study treatment, except for cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
• Patient who has had systemic therapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry
• Patient who has undergone major surgery =\< 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure
• Patient has a clinically significant cardiac disease or impaired cardiac function, such as:
• The presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association class III/IV congestive heart failure, or uncontrolled hypertension
• Documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments)
• Major abnormalities documented by echocardiography (ECHO) with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular \[LV\] ejection fraction \< 50%, evaluation based on the institutional lower limit of normal)
• Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography \[CT\] scan/magnetic resonance imaging \[MRI\] with contrast)

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

LY-2157299; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Vandana Abramson, MD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 3, 2016
• Study Start: March 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: August 1, 2023
• Last Updated: November 22, 2023

Record last verified: 2023-11

Locations

US (1)