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Metastatic Breast CancerPhase 2NCT01792050

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

A Phase 2 study testing Docetaxel, Indoximod and Paclitaxel in people with Metastatic Breast Cancer, run by NewLink Genetics Corporation at 40 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Docetaxel, Indoximod and Paclitaxel
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
169 participants
Where
40 sitesin 2 countries
Study dates
Feb 2013to 7 Jul 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

40 sites in 2 countries.

40 sites in 2 countries

United States28 sites

  • Illinois Cancer Specialists

    Arlington Heights, Illinois, 60005

  • University Cancer & Blood Center, LLC

    Athens, Georgia, 30607

  • Georgia Regents University

    Augusta, Georgia, 30912

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • University of Virginia

    Charlottesville, Virginia, 22908

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612

  • Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic - Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Wheaton Franciscan Healthcare- Reiman Cancer Center

    Franklin, Wisconsin, 53132

  • University of Florida Health Cancer Center

    Gainesville, Florida, 32610

  • Indiana University Health Goshen Center for Cancer Care

    Goshen, Indiana, 45626

  • Aurora Baycare

    Green Bay, Wisconsin, 54311

  • Pennsylvania State University Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • MD Anderson Cancer Center

    Houston, Texas, 77303

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • Lynchburg Hematology Oncology

    Lynchburg, Virginia, 24501

  • Taussig Cancer Institute

    Mayfield Heights, Ohio, 44124

  • Peninsula Cancer Center

    Newport News, Virginia, 23601

  • Paoli Hospital

    Paoli, Pennsylvania, 19301

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Eastchester Center for Cancer Care

    The Bronx, New York, 10469

  • Space Coast Cancer Center

    Titusville, Florida, 32796

  • Cleveland Clinic - Florida

    Weston, Florida, 33331

  • Wake Forest Baptist Hospital

    Winston-Salem, North Carolina, 27157

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

Other trials in United States

Poland12 sites

  • Research SiteR

    Brzozów, 36-200

  • Reserach Site

    Gdansk, 80-210

  • Research Site

    Gdynia, 85-519

  • Research Site

    Gorzów Wielkopolski, 66-400

  • Reserach Site

    Konin, 62-500

  • Research Site

    Krakow, 31-115

  • Research Site

    Olsztyn, 10-228

  • Research Site

    Olsztyn, 10-513

  • Research Site

    Poznan, 60-569

  • Research Site

    Rybnik, 44-200

  • Research Site

    Rzeszów, 35-055

  • Research Site

    Warsaw, 02-781

Other trials in Poland

About this study

Official title: A Phase II Double-Blinded, Randomized, Placebo-Controlled Study of Indoximod in Combination With a Taxane Chemotherapy in Metastatic Breast Cancer

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.

Read the 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 or paclitaxel with indoximod in metastatic breast cancer.

Being tested
Docetaxel, Placebo, Indoximod, Paclitaxel
Keywords
IDO, IDO Inhibitor, Metastatic Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DocetaxelDrug

    Also called Taxotere®

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

  • PlaceboOther

    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.

  • IndoximodDrug

    Also called 1-methyl-D-tryptophan, Indoximod, D-1MT, 1-MT

    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.

  • PaclitaxelDrug

    Also called Taxol

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

Study groups in NCT01792050
Study groupRoleWhat they receive
Arm 1A: Docetaxel + PlaceboPlacebo comparatorArm 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).
Receives: Drug: Docetaxel; Other: Placebo
Arm 1B: Docetaxel + IndoximodExperimentalArm 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).
Receives: Drug: Docetaxel; Drug: Indoximod
Arm 2A: Paclitaxel + PlaceboPlacebo comparatorArm 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).
Receives: Other: Placebo; Drug: Paclitaxel
Arm 2B: Paclitaxel + IndoximodExperimentalArm 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).
Receives: Drug: Indoximod; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 months

Secondary outcomes (4)

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

    A secondary objective of this phase 2 study is to determine the safety/toxicity (frequency and grade of adverse events) of docetaxel or paclitaxel in combination with indoximod versus docetaxel or paclitaxel plus placebo.

    Measured: 12 months

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

    A secondary objective of this phase 2 study is determining the correlation between clinical and pathologic variables and clinical benefit from docetaxel or paclitaxel and indoximod.

    Measured: 12 months

  3. Median Overall Survival

    A secondary objective of this phase 2 study is to observe median overall survival of all patients.

    Measured: 12 months

  4. Objective Response Rate (Complete Response + Partial Response)

    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 or paclitaxel + indoximod compared to docetaxel or paclitaxel plus placebo.

    Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2013 (estimated)
  2. Study startFeb 2013
  3. Primary completion1 Jul 2016
  4. Study completion7 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
169 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01792050
Sponsor's protocol ID
NLG2101
Status last verified
May 2020
First submitted
11 Feb 2013
Last updated
28 May 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 33151286

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Docetaxel, Indoximod and Paclitaxel in people with Metastatic Breast Cancer, run by NewLink Genetics Corporation at 40 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01792050, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020.

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