Genistein in Treating Patients Undergoing External-Beam Radiation Therapy for Bone Metastases

Phase I-II Trial of Genistein in Subjects Receiving Palliative External Beam Radiation Therapy for Osseous Metastases: A Study of Palliation of Symptoms and Quality of Life

RATIONALE: Genistein may increase the effectiveness of radiation therapy in treating pain caused by bone metastases.

PURPOSE: This phase I/II trial is studying the side effects of genistein and to see how well it works in treating patients undergoing external-beam radiation therapy for pain caused by bone metastases.

OBJECTIVES:

• To determine whether genistein is safe when administered in combination with palliative external beam radiotherapy in patients with osseous metastases.
• To determine the time to pain relief, duration of pain relief, and degree of pain relief in patients treated with this regimen.
• To determine the incidence of pathologic fractures in patients treated with this regimen.
• To determine the effect of this regimen on quality of life measures in these patients.

OUTLINE: This is a multicenter study.

Patients undergo external beam radiotherapy once daily on days 1-10. Patients also receive oral genistein once daily on days 1-60.

Patients complete pain and quality-of-life questionnaires periodically.

After completion of study therapy, patients are followed at 30 days.

Inclusion Criteria:

• Histologically confirmed malignant solid tumor, including any of the following:

  • Breast cancer
  • Lung cancer
  • Kidney cancer
  • Melanoma
  • Prostate cancer

• Radiographic evidence* of bone metastasis within the past 8 weeks NOTE: *Acceptable studies include plain radiograph, radionuclide bone scan, CT scan, and MRI

• Has pain that appears to be related to the radiographically documented metastasis, in the opinion of the treating physician, AND a decision has been made by the responsible clinician that a course of palliative external beam radiotherapy is appropriate treatment

  • "Worst pain score" of > 5 on a scale of 10 as scored on the pain assessment questionnaire (BPI) (question #3: 0 = no pain; 10 = worst possible pain) OR taking narcotic medications with an oral morphine equivalent dose of > 60 mg/day
  • No painful metastases to the skull, hands, or feet

• Eligible treatment sites include any of following:

  • Weight-bearing sites:

    • Pelvis (excluding pubis)
    • Femur
    • Sacrum and/or sacroiliac joints
    • Tibia

  • Non-weight-bearing sites:

    • Up to 5 consecutive cervical, thoracic, or lumbar vertebral bodies
    • Lumbosacral spine
    • Up to 3 consecutive ribs
    • Humerus
    • Fibula
    • Radius ± ulna
    • Clavicle
    • Sternum
    • Scapula
    • Pubis

• If multiple osseous sites are treated, the treatment site is included as weight-bearing if any of the sites include the pelvis, sacrum, femur, or tibia

  • Treatment of multiple osseous sites allowed only if those sites can be included in ≤ 3 treatment sites

• Patients with painful metastases that are contiguous but do not fit into the definition of a site listed above are eligible but are considered to have 2 treatment sites

• No vertebral metastases with clinical or radiographic evidence of spinal cord or cauda equina compression/effacement

• No primary hematologic malignancies (e.g., lymphoma)

• Hormone receptor status (for patients with breast cancer):

  • Estrogen receptor-negative tumor

• Menopausal status not specified

• Karnofsky performance status 40-100%

• Life expectancy ≥ 3 months

• ALT normal

• Bilirubin normal

• Serum creatinine normal (≤ 1.8 mg/dL for males and ≤ 1.5 mg/dL for females)

• Free T4 and thyroid-stimulating hormone normal

• Not pregnant

• Negative pregnancy test

• Fertile patients must use effective contraception

• No pathologic fracture or impending fracture of the treatment site

• No history of primary hyperparathyroidism

• No malabsorptive disease or chronic diarrhea

• No history of sarcoidosis or tuberculosis

Exclusion Criteria:

• Less than 30 days since prior systemic radioisotopes for pain, including Strontium-90 (^90Sr) or Samarium (^153Sm)

• Less than 30 days since prior antibiotics

• Less than 30 days since prior initiation of systemic therapy (e.g., hormonal therapy, chemotherapy, or immunotherapy)

• Less than 90 days since prior intravenous bisphosphonate therapy

  • Concurrent oral bisphosphonates allowed

• Prior radiotherapy or palliative surgery to the painful sites

• Concurrent surgical fixation of the bone

• Concurrent treatment to the skull, hands, or feet