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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by NewLink Genetics Corporation
Information provided by (Responsible Party):
NewLink Genetics Corporation Identifier:
First received: February 11, 2013
Last updated: September 12, 2014
Last verified: September 2014

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

Condition Intervention Phase
Metastatic Breast Cancer
Drug: Docetaxel
Other: Placebo
Drug: Indoximod
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Double-Blinded, Randomized, Placebo-Controlled Study of Docetaxel in Combination With 1-methyl-D-tryptophan (Indoximod) in Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by NewLink Genetics Corporation:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The primary objective of this phase 2 study is the progression free survival of docetaxel in combination with indoximod compared to docetaxel plus placebo in metastatic breast cancer.

Secondary Outcome Measures:
  • Frequency and grade of adverse events of docetaxel in combination with indoximod versus docetaxel alone [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    A secondary objective of this phase 2 study is to determine the safety/toxicity (frequency and grade of adverse events) of docetaxel in combination with indoximod versus docetaxel plus placebo.

  • Correlation of clinical and pathologic variables and clinical benefit (progression free survival rate) from treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    A secondary objective of this phase 2 study is determining the correlation between clinical and pathologic variables and clinical benefit from docetaxel and indoximod.

  • Median Overall Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    A secondary objective of this phase 2 study is to observe median overall survival of all patients.

  • Objective Response Rate (Complete Response + Partial Response) [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    A secondary objective is to determine the objective response rate (CR+PR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of docetaxel + indoximod compared to docetaxel plus placebo.

Estimated Enrollment: 154
Study Start Date: February 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm A: Docetaxel + Placebo
Arm A: 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
Docetaxel chemotherapy regimen given by vein over 1 hour on day 8 of each cycle.
Other Name: Taxotere®
Other: Placebo
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.
Experimental: Arm B: Docetaxel + Indoximod
Arm B: 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
Docetaxel chemotherapy regimen given by vein over 1 hour on day 8 of each cycle.
Other Name: Taxotere®
Drug: Indoximod
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.
Other Name: 1-methyl-D-tryptophan, Indoximod, D-1MT, 1-MT

Detailed Description:

It is estimated that 232,340 US women will be diagnosed with and 40,030 women will die of breast cancer in 2013. Metastatic breast cancer is a terminal condition and treatments are palliative in nature. The median survival for patients with metastatic breast cancer is approximately 2.5 years. The standard therapies currently in use include anti-estrogen therapies (anastrazole, letrozole, fulvestrant, tamoxifen), chemotherapy agents (taxanes, capecitabine, navelbine, gemcitabine, eribulin, ixabepilone), targeted therapies (trastuzumab, lapatinib), and supportive care agents (zolendronic acid, denosumab). While breast cancer typically responds well to treatment, the response is transient and their disease becomes more refractory with continued therapy. Also, quality of life is a significant issue for these patients as many of these therapies are associated with significant side effects. Well tolerated, novel agents which improve the efficacy of existing chemotherapy agents would prove quite useful in managing metastatic breast cancer.

Preclinical data derived from MMTV-Neu mice with autochthonous tumors studied the interaction between indoximod and various chemotherapeutic agents. Mice with 5-10mm tumors were enrolled into control and treatment groups. Mice were treated with indoximod alone, chemotherapy alone (paclitaxel, doxorubicin, cyclophosphamide, and others), and the combination of indoximod and chemotherapy. treatment with indoximod or paclitaxel alone caused retardation of tumor growth in this model but no regressions were seen. the combination of indoximod plus paclitaxel caused 30% tumor regression and histologically there was significantly enhanced tumor cell death with the combination versus either agent alone. This synergism was abrogated when the mice underwent CD4+ T cell depletion prior to treatment with the combination, suggesting the immune response played a role in the observed effect. Based on this data and other reports suggesting systemic immunomodulating drugs like indoximod can synergize with chemotherapy agents such as taxanes, the decision was made to devise this combination of therapy of docetaxel with indoximod in metastatic breast cancer.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed estrogen/progesterone receptors (ER/PR) +/-; human epidermal growth factor receptor 2 (HER2)-, metastatic breast cancer.
  • 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.
  • 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 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.

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
  • 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 1-Methyl-D-tryptophan 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 1-Methyl-D-tryptophan, breastfeeding should be discontinued if the mother is treated with 1-Methyl-D-tryptophan. Also, docetaxel is a category D cytotoxic agent and is 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01792050

United States, Florida
University of Florida Health Cancer Center Recruiting
Gainesville, Florida, United States, 32610
Contact: Alison M Ivey, RN    352-265-0680 ext 88411   
Principal Investigator: Karen C Daily, DO         
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Katie Fick, MS, CCRP    813-745-8304   
Principal Investigator: Hatem Soliman, MD         
Space Coast Cancer Center Recruiting
Titusville, Florida, United States, 32796
Contact: Linda Perez, CCRC    855-894-4673 ext 3510   
Principal Investigator: Richard Levine, MD         
Cleveland Clinic - Florida Recruiting
Weston, Florida, United States, 33331
Contact: Kim Thomas    954-659-5579   
Sub-Investigator: Thomas A Samuel, MD         
United States, Georgia
Georgia Regents University Recruiting
Augusta, Georgia, United States, 30912
Contact: Connie Edwards    706-721-1409   
Principal Investigator: Shou-Ching Tang, MD         
United States, Illinois
Illinois Cancer Specialists Recruiting
Arlington Heights, Illinois, United States, 60005
Contact: Heather Lee    847-259-0624   
Principal Investigator: Rajat Malhotra, MD         
United States, Indiana
Indiana University Health Goshen Center for Cancer Care Recruiting
Goshen, Indiana, United States, 45626
Contact: Pat Vandenburg, RN    574-364-2491   
Principal Investigator: Daniel Bruetman, MD         
United States, New York
Eastchester Center for Cancer Care Recruiting
Bronx, New York, United States, 10469
Contact: Karen Hoffman, MD    718-732-4029   
Principal Investigator: Anthony Hoffman, MD         
United States, North Carolina
University of North Carolina Withdrawn
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic - Taussig Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Ricki Englehaupt    216-636-0216   
Principal Investigator: Alberto Montero, MD         
United States, Pennsylvania
Bryn Mawr Hospital Recruiting
Bryn Mawr, Pennsylvania, United States, 19010
Contact: Diana Blade    484-476-2649   
Principal Investigator: Paul B Gilman, MD         
Pennsylvania State University Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Jo Ann Fahringer, BSN, RN, CCRC    717-531-0003 ext 285237   
Principal Investigator: Christina Truica, MD         
Paoli Hospital Recruiting
Paoli, Pennsylvania, United States, 19301
Contact: Diana Blade    484-476-2649   
Principal Investigator: Paul B Gilman, MD         
Lankenau Medical Center Recruiting
Wynnewood, Pennsylvania, United States, 19096
Contact: Diana Blade    484-476-2649   
Principal Investigator: Paul B Gilman, MD         
United States, Tennessee
University of Tennessee Medical Center Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Shanna Overbey, RN    865-305-9773   
Principal Investigator: Janakiraman Subramanian, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Snjezana Zaja-Milatovic    434-243-6575   
Principal Investigator: Patrick Dillon, MD         
Lynchburg Hematology Oncology Recruiting
Lynchburg, Virginia, United States, 24501
Contact: Donna Washburn, MSN, RN    434-200-1495   
Principal Investigator: Dwight Oldham, MD         
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Katherine Muson    804-628-4712   
Principal Investigator: Andrew Poklepovic, MD         
United States, Wisconsin
Wheaton Franciscan Healthcare- Reiman Cancer Center Recruiting
Franklin, Wisconsin, United States, 53132
Contact: Catherine Schott, BSN    414-427-2396   
Principal Investigator: Jonathan Treismann, MD         
Aurora Baycare Recruiting
Green Bay, Wisconsin, United States, 54311
Contact: Kate Newbanks, RN, BSN    920-288-4115   
Principal Investigator: Dhimant Patel, MD         
Sponsors and Collaborators
NewLink Genetics Corporation
Study Director: Nicholas Vahanian, MD NewLink Genetics Corporation
  More Information

No publications provided

Responsible Party: NewLink Genetics Corporation Identifier: NCT01792050     History of Changes
Other Study ID Numbers: NLG2101
Study First Received: February 11, 2013
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by NewLink Genetics Corporation:
IDO Inhibitor
Metastatic Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents processed this record on October 19, 2014