Beta-Glucan in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as beta-glucan, may stimulate the immune system in different ways and stop tumor cells from growing. PURPOSE: This phase I trial is studying the side effects and best dose of beta-glucan in treating patients with locally advanced or metastatic non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary To assess the feasibility and toxicity of therapy with beta-glucan MM-10-001 in patients with locally advanced or metastatic non-small cell lung cancer for which standard curative or palliative measures do not exist or are no longer effective. Secondary To explore analysis of the effect of beta-glucan MM-10-001 on the innate immune compartment, in particular natural killer cell activation and effector status. To perform correlatives (cytokine profiling) that will explore the effects of beta-glucan MM-10-001 on the cytokine profile of these patients. To document all clinical responses of these patients after treatment with beta-glucan MM-10-001. To explore potential beta-glucan MM-10-001 dose effects on the patient-reported functional status. OUTLINE: Patients receive oral beta-glucan MM-10-001 once or twice daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for correlative studies. Samples are analyzed for natural killer cell activation and effector status and cytokine profiling by flow cytometry. Patient-reported functional status is assessed at baseline and periodically during treatment by QOL-FACT-L questionnaire. After completion of study treatment, patients are followed periodically.

Official Title
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A Phase I Study of MM-10-001 In Advanced Non Small Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: beta-glucan MM-10-001
* Other: flow cytometry
* Other: laboratory biomarker analysis
* Other: questionnaire administration


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed non-small cell lung cancer Locally advanced or metastatic disease for which standard curative or palliative measures do not exist or are no longer effective Unresectable disease No active or symptomatic brain metastases unless they were previously treated by radiotherapy or surgery, stabilized, AND off steroid therapy for ≥ 4 weeks PATIENT CHARACTERISTICS: Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2 Life expectancy > 3 months WBC > 2,000/mm³ Absolute neutrophil count > 1,000/mm³ Platelet count > 50,000/mm³ Total bilirubin < 1.5 times upper limit of normal (ULN) AST and ALT < 2.5 times ULN Serum creatinine < 2.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must be able to swallow enteral medications (patients with feeding tubes are eligible) No condition or disease that affects gastrointestinal (GI) function or impairs the ability to take oral medications including any of the following: GI tract disease No intractable nausea or vomiting Malabsorption syndrome Requirement for IV alimentation Prior surgical procedures effecting absorption Uncontrolled inflammatory GI disease (e.g., Crohn disease, ulcerative colitis) No concurrent condition requiring the use of systemic or topical steroids or the use of immunosuppressive agents No history of allergic reactions attributed to compounds of similar chemical or biological composition to beta-glucan MM-10-001 No uncontrolled concurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situation that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered Concurrent palliative radiotherapy for symptoms control allowed At least 2 weeks since prior corticosteroids and no concurrent systemic or topical steroids At least 7 days since prior antioxidant supplements (vitamin C and E) No other concurrent investigational agents Bisphosphonate therapy (e.g., pamidronate or zoledronate) allowed No concurrent over-the-counter or dietary supplement containing beta-glucan (e.g., mushroom extracts, lentinan products, dried mushrooms) or other mushroom-derived powders, liquids, capsules, gels, or any other dosage form No concurrent use of immunosuppressive agents (e.g., cyclosporine and its analog) No concurrent darbepoetin alfa or epoetin alfa No concurrent colony-stimulating factors No concurrent antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (beta-glucan MM-10-001)<br>Patients receive oral beta-glucan MM-10-001 once or twice daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Biological: beta-glucan MM-10-001<br>* Dose escalation with six patients treated at each of the following oral dosages: 2.5, 5.0, 7.5, 10, 15, 20, 30, 40, 50, and 80 mg/day<br>Other: flow cytometry<br>* Performed on blood samples collected within 14 days prior to study treatment and at week 1, week 5, week 9, week 13 and every 4 weeks until the end of study treatment.<br>Other: laboratory biomarker analysis<br>* Performed on blood samples collected within 14 days prior to study treatment and at week 1, week 5, week 9, week 13 and at the end of study treatment.<br>Other: questionnaire administration<br>* Assessment pre-study and week 5, week 9, week 13 and at off study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | 28 days after therapy begins | 
| Maximum-tolerated dose |  | 28 days after therapy begins | 
| Toxicity as assessed by NCI CTCAE v3.0 |  | 28 days after therapy begins | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-glucan MM-10-001 activity as assessed by changes in natural killer cell activation and functional activity, cytokine profiling, and clinical benefit |  | 13 weeks after start of study treatment | 
| Patient-reported functional status |  | 13 weeks after start of study treatment | 
| Survival |  | 1 year after start of study | 
| Progression-free survival |  | 1 year after start of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer