Clinical trial NCT00857025: Beta-Glucan in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Phase I Study of MM-10-001 In Advanced Non Small Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: 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
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-03-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety
timeFrame: 28 days after therapy begins
measure: Maximum-tolerated dose
timeFrame: 28 days after therapy begins
measure: Toxicity as assessed by NCI CTCAE v3.0
timeFrame: 28 days after therapy begins
Secondary outcomes:
measure: Beta-glucan MM-10-001 activity as assessed by changes in natural killer cell activation and functional activity, cytokine profiling, and clinical benefit
timeFrame: 13 weeks after start of study treatment
measure: Patient-reported functional status
timeFrame: 13 weeks after start of study treatment
measure: Survival
timeFrame: 1 year after start of study
measure: Progression-free survival
timeFrame: 1 year after start of study
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Marianna Koczywas, MD
role: PRINCIPAL_INVESTIGATOR
References: