Phase II Trial of Stereotactic Radiosurgery Boost Following Surgical Resection for Brain Metastases

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00587964
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arm: 1
• Duration (Months): 55
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

For patients who have one or two metastases in the brain, the tumor(s) can often be removed with surgery to relieve symptoms from the tumor(s) and to improve survival. However, about half of all patients who have the tumor(s) removed with surgery will develop regrowth (recurrence) of the tumor. To prevent this regrowth of tumor, some patients receive radiation to the entire brain (whole brain radiation) after surgery. This involves daily treatment for about two to three weeks, and may cause long-term neurological problems, such as memory loss.

Stereotactic radiosurgery (SRS) is sometimes used instead of surgery to treat brain metastasis. This involves the use of a special head frame and sophisticated computer programs that enable us to deliver a high dose of radiation to a small focused area of the brain in only one treatment.

Research has shown that the results of treatment with SRS are as good as surgical removal of the tumor. SRS and surgical resection are considered the standard options for the treatment of brain metastases. This Phase II clinical trial is studying the combination of these two techniques. The purpose of this study is to evaluate the use of SRS following surgical removal of brain metastases. The outcomes we will be looking at are tumor regrowth after treatment and side effects of treatment.

Condition or Disease	Intervention/Treatment	Phase
Brain Metastasis; Bladder Cancer; Breast Cancer; Cervical Cancer; Colon Cancer; HEENT Cancer; Lung Cancer; Melanoma; Pancreatic Cancer; Prostate Cancer; Rectal Cancer; Sarcoma; Testicular Cancer	Radiation: Stereotactic Radiosurgery	Phase 2

Detailed Description

This is a phase II trial in patients with 1-2 brain metastases treated with surgical resection followed by stereotactic radiosurgery boost. Following surgical resection, patients would receive a stereotactic radiosurgery boost to the surgical bed, 2-8 weeks after surgery. A dose of 15 to 22 Gy would be delivered in a single fraction. Patient would be subsequently followed clinically and radiologically to watch for local control as well as toxicity. If a recurrence or new metastasis(es) is detected, further treatment may be given, consisting of chemotherapy, surgery, whole brain radiation therapy or stereotactic radiotherapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Stereotactic Radiosurgery Boost Following Surgical Resection for Brain Metastases
• Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment

Radiation: Stereotactic Radiosurgery; All patients would undergo craniotomy and the goal of surgery in all cases would be total removal of the metastases. The patient will initially receive premedication with 0.5- 1mg of Ativan orally prior to SRS procedure. Subsequently, the patient will have the stereotactic head ring placement under local anesthesia. A peripheral IV will be placed for administration of the intravenous contrast. Thin-section CT images will be obtained with intravenous contrast with head ring in place for the purpose of treatment planning. A fusion program will be used to combine the recently obtained MRI images along with the CT scans. The target volume as well as the critical structures will be contoured. SRS would be delivered using either the Brain Lab or Radionics Radiosurgery planning and delivery system. Patients would receive a single treatment ranging from 15-22 GY.; Other Names: SRS

Outcome Measures

Primary Outcome Measures

1. Local Control [1 year]

   following a combination of stereotactic radiosurgery and surgical resection for brain metastases; to determine the incidence of the brain injury following the combination therapy. Local control: Absence of radiographic evidence of tumor at the site of therapy constitutes local control of the treated disease.Recurrence in the treated region: The reappearance of tumor on any MRI or CT scan at the site of treatment constitutes recurrent disease at the treated region. Recurrence outside the treated region: The development of new intracranial metastatic foci or leptomeningeal disease constitutes recurrence outside the treated region. Leptomeningeal disease will be documented by a positive CSF cytology, abnormal myelogram or spinal MRI. No evidence of disease: Absence of clinical or radiographic evidence of tumor both at the site of therapy and elsewhere in the brain constitutes no evidence of disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed malignancy with the presence of one or two intraparenchymal brain metastases (newly diagnosed patients may be registered based on radiologic confirmation if pathology is unavailable)

• Age ≥ 18 years

• Karnofsky performance status ≥ 70

• Neurologic Function Status 0-2

• Patients may have extracranial sites of metastatic disease

• Adequate bone marrow reserve (hemoglobin ≥ 8 grams, absolute neutrophil count ≥ 1000/mm3, platelets ≥ 50,000/mm3)

• Patient must sign a study specific informed consent form.

Exclusion Criteria:

• Major medical illness including poor cardiac, pulmonary or renal status which would result in patient being a high risk candidate for neurosurgical procedure

• Inability to obtain histologic proof of malignancy

• Patients with leptomeningeal metastases documented by MRI or CSF evaluation Patients with metastases within 10 mm of the optic apparatus so that some portion of the optic nerve or chiasm would be included in the high dose SRS boost field

• Patients with metastases in the brainstem, midbrain, pons, or medulla

• Patients with small cell lung cancer, germ-cell tumors, lymphoma, leukemia and multiple myeloma are not eligible

• Younger than 18 years of age

• Karnofsky performance status of ≤ 60

• Prior history of whole brain radiation therapy

• Concomitant use of chemotherapy or targeted biological therapy (within a week of the SRS treatment)

• ≥ 3 metastases in the brain

• Allergy to both CT and MR contrast dyes

• Platelet count of < 100,000 or coagulation disorders that cannot be corrected or would render the surgery a high-risk procedure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Kathryn Beal, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering web site

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00587964
• Other Study ID Numbers: 04-061
• First Posted: Jan 8, 2008
• Last Update Posted: Feb 22, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: Cancer; Brain Metastasis; Radiosurgery; Bladder cancer; Breast cancer; Cervical cancer; Colon cancer; HEENT cancer; Lung cancer; Melanoma; Pancreatic cancer; Prostate cancer; Rectal cancer; Sarcoma; Testicular cancer; Radiation
• Additional relevant MeSH terms: Prostatic Neoplasms; Melanoma; Neoplasm Metastasis; Pancreatic Neoplasms; Sarcoma; Rectal Neoplasms; Uterine Cervical Neoplasms; Colonic Neoplasms; Urinary Bladder Neoplasms; Brain Neoplasms; Testicular Neoplasms

Study Results

Participant Flow

Arm/Group Title	Treatment - Stereotactic Radiosurgery
Arm/Group Description	Stereotactic Radiosurgery: All patients would undergo craniotomy and the goal of surgery in all cases would be total removal of the metastases.
Period Title: Overall Study
STARTED	51
COMPLETED	39
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Treatment - Stereotactic Radiosurgery
Arm/Group Description	Stereotactic Radiosurgery: All patients would undergo craniotomy and the goal of surgery in all cases would be total removal of the metastases.
Overall Participants	51
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	34 66.7%
>=65 years	17 33.3%
Sex: Female, Male (Count of Participants)
Female	33 64.7%
Male	18 35.3%

Outcome Measures

1. Primary Outcome

Title	Local Control
Description	following a combination of stereotactic radiosurgery and surgical resection for brain metastases; to determine the incidence of the brain injury following the combination therapy. Local control: Absence of radiographic evidence of tumor at the site of therapy constitutes local control of the treated disease.Recurrence in the treated region: The reappearance of tumor on any MRI or CT scan at the site of treatment constitutes recurrent disease at the treated region. Recurrence outside the treated region: The development of new intracranial metastatic foci or leptomeningeal disease constitutes recurrence outside the treated region. Leptomeningeal disease will be documented by a positive CSF cytology, abnormal myelogram or spinal MRI. No evidence of disease: Absence of clinical or radiographic evidence of tumor both at the site of therapy and elsewhere in the brain constitutes no evidence of disease.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment - Stereotactic Radiosurgery
Arm/Group Description	Stereotactic Radiosurgery: All patients would undergo craniotomy and the goal of surgery in all cases would be total removal of the metastases.
Measure Participants	39
Local Control	13 25.5%
No Evidence of Disease (NED)	23 45.1%
Progression of Disease (POD)	2 3.9%
Relapse/Recurrence	1 2%

Adverse Events

Arm/Group Title	Treatment - Stereotactic Radiosurgery
Arm/Group Description	Stereotactic Radiosurgery: All patients would undergo craniotomy and the goal of surgery in all cases would be total removal of the metastases.
All Cause Mortality
	Treatment - Stereotactic Radiosurgery
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment - Stereotactic Radiosurgery
	Affected / at Risk (%)	# Events
Total	16/51 (31.4%)
Blood and lymphatic system disorders
Blood disorder	1/51 (2%)	1
Hypomagnesemia	1/51 (2%)	1
Platelets count decrease	1/51 (2%)	1
Cardiac disorders
Thrombosis	1/51 (2%)	1
Eye disorders
Vision-blurred vision	1/51 (2%)	1
Gastrointestinal disorders
Constipation	1/51 (2%)	1
Radiation oesophagitis	1/51 (2%)	1
Nausea	2/51 (3.9%)	2
Vomiting	2/51 (3.9%)	2
General disorders
General symptom	2/51 (3.9%)	2
Headache	1/51 (2%)	2
Musculoskeletal and connective tissue disorders
Bone pain	1/51 (2%)	1
Nervous system disorders
Ischemia cerebrovascular	1/51 (2%)	1
Confusion	3/51 (5.9%)	3
Neurological disorder	2/51 (3.9%)	2
Peripheral motor neuropathy	1/51 (2%)	1
Seizure	2/51 (3.9%)	3
Syncope	1/51 (2%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/51 (3.9%)	2
Respiratory disorder	3/51 (5.9%)	3
Other (Not Including Serious) Adverse Events
	Treatment - Stereotactic Radiosurgery
	Affected / at Risk (%)	# Events
Total	0/51 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.