Study of Chemotherapy in Combination With IDO Inhibitor in Metastatic Breast Cancer

NCT01792050 | Completed Phase 2 DMC

• 1 other identifier: NLG2101
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 40

Brief Summary

The purpose of this study is to compare the effects, good and/or bad, of standard of care therapy (docetaxel or paclitaxel) with or without the addition of 1-Methyl-D-tryptophan (referred to as indoximod) an experimental drug to find out which treatment is better.

Conditions

Metastatic Breast Cancer

Keywords

IDO; IDO Inhibitor; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  The primary objective of this phase 2 study is the progression free survival of docetaxel or paclitaxel in combination with indoximod compared to docetaxel or paclitaxel plus placebo in metastatic breast cancer.

  12 months

Secondary Outcomes (4)

• Frequency and grade of adverse events of docetaxel and paclitaxel in combination with indoximod versus docetaxel alone

  12 months

• Correlation of clinical and pathologic variables and clinical benefit (progression free survival rate) from treatment

  12 months

• Median Overall Survival

  12 months

• Objective Response Rate (Complete Response + Partial Response)

  12 Months

Study Arms (4)

Arm 1A: Docetaxel + Placebo

PLACEBO COMPARATOR

Arm 1A: Docetaxel 75 mg/m\^2 IV given every 3 weeks (on day 8 of 21 day cycle), plus placebo PO BID (days 1-14 of 21 day cycle).

Drug: Docetaxel; Other: Placebo

Arm 1B: Docetaxel + Indoximod

EXPERIMENTAL

Arm 1B: Docetaxel 75 mg/m\^2 IV given every 3 weeks (on day 8 of 21 day cycle), plus Indoximod 1200 mg PO BID (days 1-14 of 21 day cycle).

Drug: Docetaxel; Drug: Indoximod

Arm 2A: Paclitaxel + Placebo

PLACEBO COMPARATOR

Arm 2A: Paclitaxel 80 mg/m\^2 IV given weekly x3 followed by a week of rest (28 day cycle), plus placebo PO BID (days 1-21 of 28 day cycle).

Other: Placebo; Drug: Paclitaxel

Arm 2B: Paclitaxel + Indoximod

EXPERIMENTAL

Arm 2B: Paclitaxel 80 mg/m\^2 IV given weekly x3 followed by a week of rest (28 day cycle), plus Indoximod 1200 mg PO BID (days 1-21 of 28 day cycle).

Drug: Indoximod; Drug: Paclitaxel

Interventions

Docetaxel DRUG

Docetaxel chemotherapy regimen given by vein over 1 hour on day 8 of each cycle.

Also known as: Taxotere®

Arm 1A: Docetaxel + Placebo; Arm 1B: Docetaxel + Indoximod

Placebo OTHER

Placebo taken orally every morning 1 hour prior to breakfast and 1 hour prior to dinner on days 1-14. Six pills to be taken each time for a total of 12 pills per day.

Arm 1A: Docetaxel + Placebo; Arm 2A: Paclitaxel + Placebo

Indoximod DRUG

Indoximod (1200 mg) taken orally every morning 1 hour prior to breakfast and 1 hour prior to dinner on days 1-14. Six 200 mg pills to be taken twice a day for a total of 12 pills per day.

Also known as: 1-methyl-D-tryptophan, Indoximod, D-1MT, 1-MT

Arm 1B: Docetaxel + Indoximod; Arm 2B: Paclitaxel + Indoximod

Paclitaxel DRUG

Paclitaxel chemotherapy regimen given by vein over 1 hour weekly x 3 followed by a week of rest each cycle.

Also known as: Taxol

Arm 2A: Paclitaxel + Placebo; Arm 2B: Paclitaxel + Indoximod

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed estrogen/progesterone receptors (ER/PR) +/-; human epidermal growth factor receptor 2 (HER2)-, metastatic breast cancer.
• Metastatic disease that is evaluable on imaging. May have measureable 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 with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. Patients can also have non-measurable disease including bone only metastatic disease, evaluated by bone scan, PET or MRI.
• Any number of prior endocrine therapies in the metastatic setting are allowed. The patient must not have received any prior chemotherapy agents in the metastatic setting. Prior treatment with adjuvant docetaxel or paclitaxel is allowed if disease relapse occurred greater than 12 months from the completion of adjuvant therapy.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Karnofsky ≥60%).
• Life expectancy of greater than 4 months.
• Patients must have normal organ and marrow function as defined below: leukocytes ≥3,000/mcL, absolute neutrophil count ≥1,500/mcL, platelets ≥100,000/mcL, total bilirubin within normal institutional limits, aspartate aminotransferase AST(SGOT)/ alanine aminotransferase ALT(SGPT) ≤2.5 X institutional upper limit of normal, creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal.
• Patients with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least 1 month off steroids.
• Male and female subjects of child producing potential must agree to use adequate forms of contraception or avoidance of pregnancy measures prior to study entry, while enrolled on study and for a minimum of one month after completion of the study.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who have had chemotherapy for the treatment of metastatic breast cancer are not eligible. Patients who have had radiotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier are not eligible.
• Patients who are currently receiving any other investigational agents.
• Patients with known active, untreated brain metastases should be excluded from this clinical trial. Those with previously treated inactive brain metastases with no evidence of active disease documented on brain MRI at least 4 weeks after radiation and off all steroids may be eligible.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or tryptophan containing substances. This would include L-tryptophan or 5-hydroxy-tryptophan supplements. Also patients with a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80 are excluded.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because indoximod is an immunoregulatory agent with the potential for abortifacient effects due to fetal rejection by the maternal immune system. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with indoximod, breastfeeding should be discontinued if the mother is treated with indoximod. Also, docetaxel and paclitaxel are category D cytotoxic agents and are not administered to pregnant females.
• Known HIV-positive patients and those with other acquired/inherited immunodeficiencies are ineligible due to the possibility of affecting the response to indoximod and the higher risk of active opportunistic infections.
• Patients with more than one active malignancy at the time of enrollment.
• Patients who have received any prior experimental active immunotherapy consisting of targeted monoclonal antibodies (ipilimumab) or pharmaceutical compounds are excluded.
• Patients with any active autoimmune disease (i.e. psoriasis, extensive atopic dermatitis, asthma, inflammatory bowel disease (IBD), multiple sclerosis (M.S.), uveitis, vasculitis), chronic inflammatory condition, or any condition requiring concurrent use of any systemic immunosuppressants or steroids for any reason would be excluded from the study. Any patient with an allo-transplant of any kind would be excluded as well. This would include those with a xenograft heart valve to avoid the potential risk of any immune reaction causing valvular degeneration. Mild-intermittent asthma requiring only occasional beta-agonist inhaler use or mild localized eczema will not be excluded.

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (40)

University of Florida Health Cancer Center

Gainesville, Florida, 32610, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Space Coast Cancer Center

Titusville, Florida, 32796, United States

Location

Cleveland Clinic - Florida

Weston, Florida, 33331, United States

Location

University Cancer & Blood Center, LLC

Athens, Georgia, 30607, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, 45626, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Eastchester Center for Cancer Care

The Bronx, New York, 10469, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest Baptist Hospital

Winston-Salem, North Carolina, 27157, United States

Location

Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic - Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Taussig Cancer Institute

Mayfield Heights, Ohio, 44124, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Pennsylvania State University Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Paoli Hospital

Paoli, Pennsylvania, 19301, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77303, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Lynchburg Hematology Oncology

Lynchburg, Virginia, 24501, United States

Location

Peninsula Cancer Center

Newport News, Virginia, 23601, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Wheaton Franciscan Healthcare- Reiman Cancer Center

Franklin, Wisconsin, 53132, United States

Location

Aurora Baycare

Green Bay, Wisconsin, 54311, United States

Location

Research SiteR

Brzozów, 36-200, Poland

Location

Reserach Site

Gdansk, 80-210, Poland

Location

Research Site

Gdynia, 85-519, Poland

Location

Research Site

Gorzów Wielkopolski, 66-400, Poland

Location

Reserach Site

Konin, 62-500, Poland

Location

Research Site

Krakow, 31-115, Poland

Location

Research Site

Olsztyn, 10-228, Poland

Location

Research Site

Olsztyn, 10-513, Poland

Location

Research Site

Poznan, 60-569, Poland

Location

Research Site

Rybnik, 44-200, Poland

Location

Research Site

Rzeszów, 35-055, Poland

Location

Research Site

Warsaw, 02-781, Poland

Location

Related Publications (1)

• Mariotti V, Han H, Ismail-Khan R, Tang SC, Dillon P, Montero AJ, Poklepovic A, Melin S, Ibrahim NK, Kennedy E, Vahanian N, Link C, Tennant L, Schuster S, Smith C, Danciu O, Gilman P, Soliman H. Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2021 Jan 1;7(1):61-69. doi: 10.1001/jamaoncol.2020.5572.

  PMID: 33151286 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; 1-methyltryptophan; Paclitaxel

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2013
• First Posted: February 15, 2013
• Study Start: February 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 7, 2017
• Last Updated: May 28, 2020

Record last verified: 2020-05

Locations

PL (12); US (28)