Conformal Radiation Therapy in Treating Patients With Metastatic Cancer Outside the Brain

A Phase II Study of Hypofractionated Highly Conformal Radiation With Helical Tomotherapy for Extra-Cranial Oligo

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This phase II trial is studying how well conformal radiation therapy works in treating patients with metastatic cancer outside the brain.

Study Overview

• Status: Terminated
• Conditions: Sarcoma; Kidney Cancer; Ovarian Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Metastatic Cancer; Melanoma (Skin)
• Intervention / Treatment: Other: questionnaire administration; Radiation: 3-dimensional conformal radiation therapy; Radiation: hypofractionated radiation therapy; Radiation: image-guided radiation therapy; Radiation: tomotherapy

Detailed Description

OBJECTIVES:

Primary

• To evaluate local control (defined as absence of local progression) at all treated sites of metastatic disease in patients with extracranial oligometastases treated with ablative doses of highly conformal radiotherapy delivered with helical tomotherapy.
• To evaluate local control at each treated site of metastatic disease in these patients.

Secondary

• To determine median time to local progression in patients treated with this regimen.
• To evaluate interfraction and intrafraction motion with megavoltage computed tomography (CT) imaging based on site of metastasis in these patients.
• To compare tumor growth during systemic therapy in tumors treated with targeted radiotherapy vs newly developed tumors that have not been treated with radiotherapy.
• To evaluate if treatment with hypofractionated highly conformal radiotherapy with helical tomotherapy can improve pain scores and decrease the need for analgesia in these patients.

OUTLINE: Patients are stratified according to histology (renal cell carcinoma vs melanoma vs sarcoma vs other histologies).

Patients undergo hypofractionated highly conformal radiotherapy with helical tomotherapy once every other day over 5 days for a total of 3 fractions. Patients undergo megavoltage imaging before and after each fraction to verify the positioning of each target lesion.

Patients complete a pain assessment questionnaire at baseline and at 1 and 3 months after treatment.

After completion of study therapy, patients are followed at 1 and 3 months and then every 3 months for up to 1 year.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

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 cancer

  • No active disease at the primary site as assessed by physical examination, clinical evaluation, or site-specific imaging

• Measurable metastatic disease meeting the following criteria:

  • Four or fewer sites of extracranial lesions < 5 cm in size

  • If metastatic site(s) is within the lung, the following criteria must be met:

    • No more than two metastases in the proximal bronchial tree area (defined as 2 cm from the trachea or mainstem bronchi)
    • Carbon monoxide diffusing capacity (DLCO) > 30% predicted and forced expiratory volume 1 (FEV1) > 1.2 L (in patients with more than one metastatic site in the lungs)
  • If metastatic site(s) is within 2 cm of either kidney, creatinine level must be < 1.5 times upper limit of normal (ULN)
  • If metastatic site(s) is within 2 cm of the liver, bilirubin level must be < 1.5 times ULN

• Patients with metastatic disease that meets any of the following criteria are excluded:

  • Proposed site(s) of treatment has been previously treated with radiotherapy
  • Metastatic site(s) requires emergent treatment (e.g., spinal cord compression, cauda equina, airway compromise, or life-threatening end-organ dysfunction)
  • Disease that is untreated or previously treated and progressive in the brain
  • Pathologic fracture or impending pathologic fracture at the metastatic site
  • Metastatic site(s) of a disease histology that is known to be sensitive to low doses of radiotherapy (e.g., pure seminoma, lymphoma, or small cell carcinoma)
• Patients in whom surgery is deemed an appropriate option as standard of care (e.g., isolated lung metastasis from sarcoma or isolated liver metastasis from colon cancer) but who refuse surgical therapy are eligible

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy > 12 weeks as assessed by the consulting radiation oncologist
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of lupus erythematosus or scleroderma
• No known hypersensitivity to therapeutic radiotherapy
• No other malignancy within the past 2 years except nonmelanoma skin cancer or in situ malignancies of the cervix, bladder, or head and neck
• No unrelated systemic illness that, in the judgment of the investigator, would compromise the patient's ability to tolerate study therapy or would likely interfere with study procedures or results
• Able or likely to adhere to study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 2 weeks since prior and no concurrent chemotherapy
• Prior or concurrent hormonal agents, including antiandrogens, gonadotropin-releasing hormone agonists, aromatase inhibitors, tamoxifen, or similar agents allowed
• No change in systemic therapy for 6 weeks before or within 4 weeks after initiating study radiotherapy

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: Radiation Therapy in Metastatic Cancer; Patients undergo hypofractionated highly conformal radiotherapy with helical tomotherapy once every other day over 5 days for a total of 3 fractions.

Other: questionnaire administration; Patients complete a pain assessment questionnaire, Brief Pain Inventory at baseline and at 1 and 3 months after treatment.; Other Names: Brief Pain Inventory; Radiation: 3-dimensional conformal radiation therapy; Conformal radiation therapy improves the ability to spare normal tissues.; Radiation: hypofractionated radiation therapy; Hypofractionated radiation therapy is delivered to maximize pain relief while minimizing patient impact if life expectancy is short.; Radiation: image-guided radiation therapy; Image guided radiation therapy targets the specific site of disease.; Radiation: tomotherapy; Tomotherapy is a delivery method which provides megavoltage computed tomography (CT) localization and may provide superior conformality and localization compared to other dynamic intensity modulated radiation therapy techniques.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month Local Control (i.e., Complete Response, Partial Response, or Stable Disease) at All Treated Sites of Metastatic Disease	Local control (e.g. absence of local progression) is defined as Complete response (CR), partial response (PR) or stable disease (SD) of the treated site(s). Complete response is the disappearance of the target lesion. Partial response is a >/= 50% decrease in maximal dimension compared to pretreatment imaging. Stable disease does not qualify for CR, PR, or progression.Progression is an interval increase in the maximal dimension of the target lesion.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.	9 months, 11 days
Median Time to Local Progression	Interval from initiation of treatment on protocol to symptomatic or radiographic progression.	6-12 months
12 Month Local Control in All Sites of Treatment, and at Each Site of Treatment	Local control (e.g. absence of local progression) is defined as Complete response (CR), partial response (PR) or stable disease (SD) of the treated site(s). Complete response is the disappearance of the target lesion. Partial response is a >/= 50% decrease in maximal dimension compared to pretreatment imaging. Stable disease does not qualify for CR, PR, or progression. Progression is an interval increase in the maximal dimension of the target lesion.	12 months
Interfraction and Intrafraction Motion With Megavoltage Computed Tomography (CT) Based on Sites of Metastasis	Megavoltage localization scans will be obtained and the physician and therapist will evaluate the cone beam image and compare this image to the expected image based on the patient's initial planning CT scan.	One to three months of followup
Pain at Sites of Metastases	Improvement in pain from baseline will be assessed by the Brief Inventory for Pain criteria.	One and three months of follow up
Tumor Doubling Times During Systemic Treatment Compared Between Tumors Untreated With Radiation (Newly Developed Tumors) and Tumors Which Have Received Radiation Therapy	Rate of growth of the composite (total) treated volume (up to four sites) compared to the composite volume of up to four newly identified and untreated prospectively-identified (at the time of systemic progression) metastatic sites. Volume doubling time will be calculated assuming an exponential growth pattern.	Baseline and prior to termination of systemic therapy or protocol withdrawal

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Deborah E. Citrin, MD, NCI - Radiation Oncology Branch; ROB

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (ACTUAL): May 1, 2010
• Study Completion (ACTUAL): May 1, 2010

Study Registration Dates

• First Submitted: October 25, 2007
• First Submitted That Met QC Criteria: October 25, 2007
• First Posted (ESTIMATE): October 30, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): January 13, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; unspecified adult solid tumor, protocol specific; bone metastases; chondrosarcoma; recurrent melanoma; stage IV melanoma; liver metastases; stage IV adult soft tissue sarcoma; recurrent adult soft tissue sarcoma; stage IV uterine sarcoma; recurrent uterine sarcoma; ovarian sarcoma; metastatic osteosarcoma; recurrent osteosarcoma; lung metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neuroendocrine Tumors; Nevi and Melanomas; Sarcoma; Kidney Neoplasms; Neoplasm Metastasis; Melanoma
• Other Study ID Numbers: 070230; NCI-07-C-0230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO