Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alobresib (Formerly GS-5829) in Adults With Advanced Solid Tumors and Lymphomas and in Combination With Exemestane or Fulvestrant in Adults With Estrogen Receptor Positive Breast Cancer

NCT02392611 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-350-15992016-001912-39
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objectives of this study are to characterize the safety and tolerability and determine the maximum tolerated dose (MTD) or recommended dose for phase 2 study (RDP2) of alobresib as a monotherapy in participants with advanced solid tumors and lymphomas, and in combination with exemestane or fulvestrant in participants with advanced estrogen receptor positive breast cancer.

Conditions

Solid Tumors and Lymphomas

Keywords

Estrogen Receptor Positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

  A DLT was a toxicity, considered possibly related to alobresib, and which occurred during DLT assessment window (Day 1 through Cycle 1 Day 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/mm\^3); Grade ≥3 neutropenia (ANC\< 1000/mm\^3) with fever (a single temperature of \> 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour \[hr\]); Grade ≥ 3 thrombocytopenia; Grade ≥ 2 bleeding; Grade ≥ 3 non hematologic toxicity, except Grade 3 nausea or emesis with maximum duration of 48 hrs on adequate medical therapy and Grade 3 diarrhea which persists for \< 72 hrs in absence of maximal medical therapy; Grade ≥ 2 non hematologic treatment-emergent adverse event (TEAE) of potential clinical significance; treatment interruption ≥ 7 days due to unresolved toxicity; and any Grade 3 or 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to alobresib.

  Baseline (Day 1) up to 28 days

Secondary Outcomes (6)

• Pharmacokinetic (PK) Parameter: Cmax of Alobresib

  Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

• PK Parameter: Ctau of Alobresib

  Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)

• PK Parameter: AUC0-24 of Alobresib

  Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

• PK Parameter: AUCtau of Alobresib

  Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)

• PK Parameter: Tmax of Alobresib

  Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

Study Arms (9)

Monotherapy: Alobresib 0.6 mg

EXPERIMENTAL

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 0.6 mg to determine the MTD.

Drug: Alobresib

Monotherapy: Alobresib 1.4 mg

EXPERIMENTAL

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 1.4 mg to determine the MTD.

Drug: Alobresib

Monotherapy: Alobresib 2 mg

EXPERIMENTAL

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 2 mg to determine the MTD.

Drug: Alobresib

Monotherapy: Alobresib 3 mg

EXPERIMENTAL

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 3 mg to determine the MTD.

Drug: Alobresib

Monotherapy: Alobresib 4 mg

EXPERIMENTAL

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 4 mg to determine the MTD.

Drug: Alobresib

Monotherapy: Alobresib 6 mg

EXPERIMENTAL

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 6 mg to determine the MTD.

Drug: Alobresib

Combination Therapy: Alobresib 2 mg + Exemestane

EXPERIMENTAL

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with exemestane 25 mg.

Drug: Alobresib; Drug: Exemestane

Combination Therapy: Alobresib 2 mg + Fulvestrant

EXPERIMENTAL

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with fulvestrant 500 mg.

Drug: Alobresib; Drug: Fulvestrant

Combination Therapy: Alobresib 3 mg + Fulvestrant

EXPERIMENTAL

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 3 mg in combination with fulvestrant 500 mg.

Drug: Alobresib; Drug: Fulvestrant

Interventions

Alobresib DRUG

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Also known as: GS-5829

Combination Therapy: Alobresib 2 mg + Exemestane; Combination Therapy: Alobresib 2 mg + Fulvestrant; Combination Therapy: Alobresib 3 mg + Fulvestrant; Monotherapy: Alobresib 0.6 mg; Monotherapy: Alobresib 1.4 mg; Monotherapy: Alobresib 2 mg; Monotherapy: Alobresib 3 mg; Monotherapy: Alobresib 4 mg; Monotherapy: Alobresib 6 mg

Exemestane DRUG

Tablets administered orally once daily on Cycle 1 Day 1 of 28 days cycle

Also known as: Aromasin®

Combination Therapy: Alobresib 2 mg + Exemestane

Fulvestrant DRUG

Administered intramuscularly on Cycle 1 Day 1 of 28 days cycle and every 28 days

Also known as: Faslodex®

Combination Therapy: Alobresib 2 mg + Fulvestrant; Combination Therapy: Alobresib 3 mg + Fulvestrant

Eligibility Criteria

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

You may qualify if:

• Group 1: Histologically or cytologically confirmed advanced malignant solid tumor or lymphoma (any subtype) that is refractory to or intolerant of standard therapy or for which no standard therapy is available
• Group 2: Post-menopausal women with advanced stage estrogen receptor positive breast cancer who are candidates for exemestane or fulvestrant
• Group 3: Individuals with lymphoma are limited to diffuse large B-cell lymphoma and peripheral T-cell lymphoma that are refractory to or intolerant of standard therapy or for which no standard therapy is available
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
• Adequate organ function defined as follows:
• Hematologic: Platelets ≥ 100 x 10\^9/L; Hemoglobin ≥ 9.0 g/ dL; Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (without platelet transfusion or any growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit). Participants in the Group 3 lymphoma expansion may be enrolled with an ANC of ≥ 1.0 x 10\^9 /L; Platelets ≥ 75 x 10\^9 /L.
• Hepatic: Aspartate transaminase (AST) / Alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
• Renal: Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 ml/min as calculated by the cockcroft-gault method
• Coagulation: International Normalized Ratio (INR) ≤ 1.2

You may not qualify if:

• Known brain metastasis or leptomeningeal disease
• Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification \> Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of study Day 1
• Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of first dose of study drug
• History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (\> 450 ms for males and \> 470 ms for females). Individuals who screen-fail due to this criterion are not eligible to be re-screened
• Clinically significant bleeding within 28 days of study Day 1
• Known human immunodeficiency virus (HIV) infection
• Hepatitis B surface antigen positive
• Hepatitis C virus (HCV) antibody positive
• No active anticoagulation within 7 days of study Day 1; including acetylsalicylic acid, low molecular weight heparin, or warfarin.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (4)

Unknown Facility

Scottsdale, Arizona, United States

Location

Unknown Facility

Fort Wayne, Indiana, United States

Location

Unknown Facility

Goshen, Indiana, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

exemestane; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2015
• First Posted: March 19, 2015
• Study Start: March 16, 2015
• Primary Completion: October 11, 2017
• Study Completion: October 11, 2017
• Last Updated: December 29, 2020
• Results First Posted: December 29, 2020

Record last verified: 2020-12

Locations

US (4)