Study of Indoximod in Metastatic Breast Cancer

Phase 1

• Conditions: Metastatic Breast Cancer; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003540-12-PL
• Lead Sponsor: ewLink Genetics Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-13
• Last Update Posted: 30 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 169

Inclusion Criteria

1. Patients must have histologically or cytologically confirmed ER/PR +/–; HER2 –, metastatic breast cancer.
2. Patients must have metastatic disease that is evaluable on imaging studies. Patients may have measurable 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 only as defined by RECIST 1.1, particularly patients with bone only metastatic disease. These patients are also eligible if their disease can be documented /evaluated by bone scans, PET, or MRI.
3. 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 6 months from the completion of adjuvant therapy.
4. Age >18 years. Because no dosing or adverse event data are currently available on the use of docetaxel or paclitaxel in combination with indoximod in patients <18 years of age, children are excluded from this study.
5. ECOG performance status <1 (Karnofsky >60%).
6. Life expectancy of greater than 4 months.
7. Patients must have normal organ and marrow function as defined in the study protocol.
8. 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.
9. The effects of indoximod on the developing human fetus are unknown. For this reason and because indoximod may affect maternal immune tolerance of the fetus, sexually active women of child-bearing potential must agree to use adequate forms of contraception prior to study entry and for the duration of study participation. Use of contraception or abstinence should continue for a minimum of 1 month after completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should discontinue the study drug and inform her treating physician immediately. Also men should be discouraged from fathering children while on treatment.
10. Ability to understand and the willingness to sign a written informed consent document.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion Criteria

1. 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.
2. Patients who are currently receiving any other investigational agents.
3. Patients with known active, untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that
would confound the evaluation of neurologic and other adverse events. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Patients with more than one active malignancy at the time of enrollment.
9. Patients who have received any prior experimental active immunotherapy consisting of targeted monoclonal antibodies (ipilimumab) or pharmaceutical compounds are excluded.
10. Patients with any active autoimmune disease (i.e. psoriasis, extensive atopic dermatitis, asthma, IBD, M.S., uveitis, vasculitis), chronic inflammatory condition, or any condition requiring concurrent use of
any systemic immunosupressants 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified