Taselisib and Enzalutamide in Treating Patients With Androgen Receptor Positive Triple-Negative Metastatic Breast Cancer

NCT02457910 | Terminated Phase 1 Results DMC

• 5 other identifiers: VICC BRE 1374NCI-2015-00795GO28972TBCRC 032P30CA068485
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 12

Brief Summary

This partially randomized phase Ib/II trial studies the side effects and best dose of taselisib when given together with enzalutamide and to see how well they work in treating patients with androgen receptor positive triple-negative breast cancer that has spread to other places in the body. Taselisib is a PI3K inhibitor. The PI3K pathway is involved is cancer growth. Androgen may cause the growth of tumor cells. Enzalutamide may stop the growth of tumor cells by blocking the androgen receptor from working. Giving taselisib with enzalutamide may be a better treatment for patients with breast cancer.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Clinical Benefit Rate (CBR) - Phase II

  CBR is defined as the proportion of patients with a best response of complete response (CR), partial response (PR), or (SD) stable disease per RECIST criteria 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. It is calculated as the mean of binomial distribution.

  At 16 weeks

• Maximum Tolerated Dose (MTD) of Taselisib Combined With 160mg Enzalutamide - Phase I

  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. Dose limiting toxicity will be graded according to the National Cancer Institute CTCAE version 4.0.

  4 weeks

Secondary Outcomes (2)

• Overall Progression-Free Survival (PFS) of Patients Treated With Enzalutamide and Taselisib

  Time from course 1, day 1 until objective tumor progression, assessed up to 3 years

• Pharmacokinetic Profile

  Approximately 4 months

Study Arms (7)

Taselisib 2 mg

EXPERIMENTAL

Patients receive taselisib PO QD on days 1-28 and enzalutamide PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to enzalutamide may continue to receive taselisib.

Other: Biomarker Analysis; Drug: Enzalutamide; Other: Pharmacological Study; Drug: Taselisib

Enzalutamide

ACTIVE COMPARATOR

Patients receive enzalutamide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients may crossover to receive Enzalutamide + Taselisib

Other: Biomarker Analysis; Drug: Enzalutamide; Other: Pharmacological Study

Taselisib 4 mg

EXPERIMENTAL

Patients receive taselisib PO QD on days 1-28 and enzalutamide PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to enzalutamide may continue to receive taselisib.

Other: Biomarker Analysis; Drug: Enzalutamide; Other: Pharmacological Study; Drug: Taselisib

Taselisib 6 mg

EXPERIMENTAL

Patients receive taselisib PO QD on days 1-28 and enzalutamide PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to enzalutamide may continue to receive taselisib.

Other: Biomarker Analysis; Drug: Enzalutamide; Other: Pharmacological Study; Drug: Taselisib

Taselisib 8 mg

EXPERIMENTAL

Patients receive taselisib PO QD on days 1-28 and enzalutamide PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to enzalutamide may continue to receive taselisib.

Other: Biomarker Analysis; Drug: Enzalutamide; Other: Pharmacological Study; Drug: Taselisib

Enzalutamide + Taselisib

EXPERIMENTAL

Patients receive enzalutamide PO QD starting on day 1 of cycle 1, and will receive Taselisib PO QD starting on day 1 of cycle 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Biomarker Analysis; Drug: Enzalutamide; Other: Pharmacological Study; Drug: Taselisib

Cross-Over

EXPERIMENTAL

Upon progression of disease, patients on the enzalutamide only arm will be allowed to crossover to enzalutamide + taselisib (must begin no later than 21 days after the clinic visit at which disease progression is determined) Enzalutamide and Taselisib will be taken PO QD

Other: Biomarker Analysis; Drug: Enzalutamide; Other: Pharmacological Study; Drug: Taselisib

Interventions

Biomarker Analysis OTHER

Correlative studies

Cross-Over; Enzalutamide; Enzalutamide + Taselisib; Taselisib 2 mg; Taselisib 4 mg; Taselisib 6 mg; Taselisib 8 mg

Enzalutamide DRUG

Given PO

Also known as: MDV3100, Xtandi

Cross-Over; Enzalutamide; Enzalutamide + Taselisib; Taselisib 2 mg; Taselisib 4 mg; Taselisib 6 mg; Taselisib 8 mg

Pharmacological Study OTHER

Correlative studies

Cross-Over; Enzalutamide; Enzalutamide + Taselisib; Taselisib 2 mg; Taselisib 4 mg; Taselisib 6 mg; Taselisib 8 mg

Taselisib DRUG

Given PO

Also known as: GDC-0032

Cross-Over; Enzalutamide + Taselisib; Taselisib 2 mg; Taselisib 4 mg; Taselisib 6 mg; Taselisib 8 mg

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
• For phase 1b: HER2 negative, as defined for phase II; any ER/PR (negative or positive) can be enrolled in the phase 1b portion
• For phase II: ER negative (defined as expression of ER in =\< 1% cells), PR negative (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/centromere on chromosome 17 \[CEN17\] ratio \< 2, and/or chromogenic in situ hybridization \[CISH\] with HER2/CEN-17 ratio \< 2), as previously documented by histological analysis
• Androgen receptor positivity, defined as \>= 10% of tumor cell nuclei with immunoreactivity for AR on central review at Vanderbilt
• Measurable or bone-only evaluable disease; measurable disease is 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, with radiologic scans within 21 days of day 1, cycle 1
• Any number of prior therapies as long as patients have adequate performance status and meet all other eligibility criteria
• Prior treatment with anti-androgens other than enzalutamide is acceptable
• Phase 1b only: Formalin-fixed paraffin embedded blocks (FFPB) or fresh frozen tissue from the original diagnosis or the metastatic setting should be located; tissue must be submitted with 3 weeks of study initiation
• Phase II only: Biopsy of a metastatic lesion in patients with reasonably accessible metastatic lesions (chest wall, skin, subcutaneous tissue, lymph nodes, skin, breast, bones, lung, and liver metastases); if a reasonably accessible metastatic lesion is not available, the patient may go on study provided that archived tissue is available; however, if a reasonably accessible site is available for biopsy, the patient must agree to biopsy; any patients not undergoing biopsy must be approved for study enrollment by the Protocol Chair; biopsies may be done with local anesthesia or intravenous conscious sedation, according to institutional guidelines; if a biopsy requires general anesthesia, then it is only allowed if acquisition of tissue is clinically indicated, and excess tissue may be collected for research purposes; patients without sites available for biopsy must have available tissue (archived formalin-fixed paraffin embedded blocks \[FFPB\] or fresh frozen tissue from original diagnosis or metastatic setting) for correlative studies; tissue needs to be located and available at the time of registration (tissue needs to be submitted within 3 weeks of study initiation)
• Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained within 28 days of starting treatment. Labs are to be repeated on cycle 1, day 1 and must still meet eligibility. These include:
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet count \>= 75,000/mm\^3
• Hemoglobin (HgB) \>= 9 g/dL

You may not qualify if:

• Any kind of malabsorption syndrome significantly affecting gastrointestinal function, including history of Crohn's disease or inflammatory bowel disease
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol; patients must have discontinued the above cancer therapies for 1 week prior to the first dose of study medication, as well as recovered to baseline from toxicity induced by previous treatments; any investigational drugs should be discontinued 2 weeks prior to the first dose of study medication and radiotherapy must have been completed \>= 2 weeks prior to initiation of study drug (cycle 1, day 1)
• Prior use of PI3K or Akt inhibitors in the metastatic setting for the treatment of cancer; these include, but are not limited to: taselisib, GDC-0941, GDC-0980, BEZ235, BKM120, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D-87503, D-106669, GSK615, CAL101; patients who have received PI3K/Akt inhibitors previously for \< 4 weeks will be eligible
• Prior treatment with enzalutamide
• Current or previously treated brain metastasis or active leptomeningeal disease; head imaging is required during screening in all patients to exclude the presence of central nervous system (CNS) metastatic disease
• History of seizure or any condition that may predispose to seizure; history of loss of consciousness or transient ischemic attack within 12 months before day 1
• Pregnant or lactating women
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring parenteral antibiotics
• Impairment of lung function (chronic obstructive pulmonary disease \[COPD\] \> grade 2, lung conditions requiring oxygen therapy) or current dyspnea at rest
• Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)
• Known left ventricular ejection fraction (LVEF) \< 50%
• Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
• Uncontrolled hypertension (systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 100 mm Hg, found on two consecutive measurements separated by a 1 or 2-week period despite adequate medical support)
• Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment \[National Cancer Institute-Common Terminology Criteria for Adverse Events, version 4.0, grade 3\])

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Translational Breast Cancer Research Consortium: collaborator
• Conquer Cancer Foundation: collaborator
• Genentech, Inc.: collaborator

Study Sites (12)

University of Alabama, Birmingham

Birmingham, Alabama, 35249, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 47405, United States

Location

John Hopkins University

Baltimore, Maryland, 21218, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Baylor Breast Center

Houston, Texas, 77030, United States

Location

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

enzalutamide; 2-(3-(2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Vandana Abramson, MD
• Organization: Vanderbilt University Medical Center

vandana.abramson@vumc.org

(615)936-8422

Study Officials

• Vandana Abramson, MD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: May 29, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: August 8, 2022
• Last Updated: August 22, 2022
• Results First Posted: May 7, 2020

Record last verified: 2022-08

Locations

US (12)