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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: beta-glucan MM-10-001; Other: flow cytometry; Other: laboratory biomarker analysis; Other: questionnaire administration

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Treatment (beta-glucan MM-10-001); 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; 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; Other: flow cytometry; 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.; Other: laboratory biomarker analysis; 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.; Other: questionnaire administration; Assessment pre-study and week 5, week 9, week 13 and at off study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 21, 2008
• Primary Completion (ACTUAL): November 24, 2010
• Study Completion (ACTUAL): May 18, 2021

Study Registration Dates

• First Submitted: March 5, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (ESTIMATE): March 6, 2009

Study Record Updates

• Last Update Posted (ACTUAL): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: 07243; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-07243; CDR0000634737 (REGISTRY: NCI PDQ)