Radiosurgery for Patients With Oligometastatic Disease at Initial Presentation

Phase 2

Terminated

Conditions: Oligometastatic Disease

Interventions: Radiation: Stereotactic Radiosurgery (SRS)
Drug: Chemotherapy

Registration Number: NCT01345539

Lead Sponsor: Steven Burton

Brief Summary: This study will evaluate the feasibility of radiosurgery for all metastatic sites in patients presenting with oligometastatic disease, defined here as 5 or fewer sites of metastatic disease involving 3 or fewer organ systems.

Detailed Description: Death from metastatic cancer is a common cause of death, accounting for 80-90% of cancer deaths. The classic thought process is that metastatic disease represents the continuum such that known metastatic disease is an inevitable harbinger for subsequent metastatic disease. However, it has been reported that a subset of patients with limited volume metastatic disease may have a better prognosis if given aggressive therapy. This group of patients has become known as "oligometastatic". These patients are potentially curable with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) (collectively referred to as stereotactic body radiotherapy or SBRT) to the metastatic disease sites in combination with standard curative therapy to the primary site. Patients in this study receive SRS/SBRT to all sites of oligometastatic disease.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Pathologically (histologically or cytologically) proven diagnosis of solid malignancy within 8 weeks of registration
Eligible disease sites include the following
- Breast
- Prostate
- GI (including colorectal, anal, esophagus, pancreas, gastric with the exception of colon cancer with resectable liver-only lesions)
- Head and neck
- Skin (melanoma and squamous cell carcinoma)
- Lung (both small cell and non-small cell)
- Sarcoma (both soft tissue and bone)
- Gynecologic (endometrial, cervical, ovarian, vaginal, vulvar)
Patients are stage IV (M1) with any combination of T and N with oligometastatic disease as defined by 5 or fewer total sites of metastatic disease involving 3 or fewer organ systems

1 Examples of patients eligible for trial

T3N2M1 NSCLC with 1 CNS metastatic lesion, 2 liver lesions, and 1 adrenal lesion.
T4N1M1 colorectal cancer with 1 liver lesion, 4 bone lesions
T3N0M1 gastric cancer with 1 supraclavicular lymph node, 2 liver lesions, and 2 CNS lesions 4Metastatic disease sites must be treatable with SRS (at discretion of treating physician).

5Primary disease site must be able to be treated with curative intent 6Zubrod Performance Status 0-1 7Age ≥ 18 8CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function defined as follows:
Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
Platelets ≥ 100,000 cells/mm3;
Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.); 9Women of childbearing potential and male participants must practice adequate contraception 10Patient must provide study specific informed consent prior to study entry.

Exclusion Criteria

Ineligible disease sites include the following
- Lymphoma
- Leukemia
- Multiple myeloma
- Primary CNS
- Peritoneal carcinomatosis
- Colon cancer with resectable liver-only lesions
Examples of patients ineligible for trial
- T1N1M1 NSCLC with 1 CNS lesion, 1 bone lesion, 1 adrenal lesion and a cervical lymph node (4 sites of metastatic disease)
- T2N1M1 Gastric cancer with 6 liver lesions (more than 5 sites of metastatic disease)
Other
- Lung cancer with pleural effusion (wet IIIB) are not eligible
- Recurrent cancers are not eligible
- Diffuse metastatic spread confined to one organ system is ineligible; examples of this include leptomeningeal spread in the CNS and peritoneal carcinomatosis.
Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable but cannot have any other primary cancer diagnosed or treated within the last 3 years other than cutaneous skin cancers. Patient may have previous chemotherapy as treatment of this previous malignancy as long as the chemotherapy has completed more than 3 years ago.
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
- Transmural myocardial infarction within the last 6 months;
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
- Immuno-compromised patients.
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Oligometastatic disease sites not eligible based on concern for toxicity:
- trachea involvement (direct invasion, tumors close to or abutting trachea are eligible)
- heart (direct invasion or involvement, pericardial lymph nodes can be treated)
Patients unable to have an FDG-PET/CT scan, either through insurance coverage, patient decision or other reason are not eligible for this study.
Patients unable to have SRS through insurance coverage or ability to pay for SRS

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stereotactic Body Radiotherapy (SBRT) with/without chemotherapy	Stereotactic Radiosurgery (SRS)	Sequence of therapy: SRS/SBRT will be used for all sites of metastatic disease in close approximation to initiation of treatment for the primary disease site (within 6 weeks). Ideally, SRS/SBRT would occur first followed by treatment to primary site. However, in some circumstances surgical resection of the primary site could precede SRS/SBRT, especially if surgical resection is required for pathological confirmation of disease. Chemotherapy choice of agents is at the discretion of the treating medical oncologist; chemotherapy may be initiated after stereotactic radiosurgery treatment of the primary disease site has been completed.
Stereotactic Body Radiotherapy (SBRT) with/without chemotherapy	Chemotherapy	Sequence of therapy: SRS/SBRT will be used for all sites of metastatic disease in close approximation to initiation of treatment for the primary disease site (within 6 weeks). Ideally, SRS/SBRT would occur first followed by treatment to primary site. However, in some circumstances surgical resection of the primary site could precede SRS/SBRT, especially if surgical resection is required for pathological confirmation of disease. Chemotherapy choice of agents is at the discretion of the treating medical oncologist; chemotherapy may be initiated after stereotactic radiosurgery treatment of the primary disease site has been completed.

Primary Outcome Measures

Name	Time	Method
Acceptable Toxicity of SRS/SBRT	Up to 3 Years (per patient)	Number of distinct patients with toxicities of Grade 3 or less per CTCAE v4.0
Presence of Multiple Metastatic Sites	Up to 3 years (per patient)	The presence of multiple metastatic disease sites (between 2 and 5 sites).

Secondary Outcome Measures

Name	Time	Method
The Functional Assessment of Cancer Therapy - General (FACT-G) Quality of Life Score	At pre-treatment	The Functional Assessment of Cancer Therapy - General (FACT-G) Quality of life Assessment is a patient self-administered 27-item questionnaire that measures health state in cancer patients in prior 7 days, including physical (PW), social (SW), emotional (EW), and functional (FW) well-being. Scoring: Five-point scale for each of the subscales is: 0 (not at all) to 4 (very much). PW has a Score range from 0-28. SW has a Score range from 0-28. EW has a Score range from 0-24. FW has a Score range from 0-28. Total overall score is thus from minimum of 0 to maximum of 108. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.
The Functional Assessment of Cancer Therapy - General (FACT-G) Quality of Score	At post-treatment	The Functional Assessment of Cancer Therapy - General (FACT-G) Quality of life Assessment is a patient self-administered 27-item questionnaire that measures health state in cancer patients in prior 7 days, including physical (PW), social (SW), emotional (EW), and functional (FW) well-being. Scoring: Five-point scale for each of the subscales is: 0 (not at all) to 4 (very much). PW has a Score range from 0-28. SW has a Score range from 0-28. EW has a Score range from 0-24. FW has a Score range from 0-28. Total overall score is thus from minimum of 0 to maximum of 108. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.
Local Control of Metastatic Disease	Up to 5 years (per patient)	Proportion of patients with local Complete Response (CR), Partial Response (PR) or Stable Disease (SD) after trial therapy as measured according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at sites of metastatic disease. Per RECIST: (CR): Disappearance of all target lesions; (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Local Control of Primary Disease	Up to 5 years	Proportion of patients with local Complete Response (CR), Partial Response (PR) or Stable Disease (SD) after trial therapy as measured according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at primary disease sites. Per RECIST: (CR): Disappearance of all target lesions; (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Analysis of Patterns of Failure Post-SRS/SBRT	Up to 5 years (per patient)	The number of patients that experience oligometastatic disease progression/recurrence after treatment for their primary disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at primary disease sites. Per RECIST, Progressive Disease (PD) includes the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Two-year Overall Survival	At 2 years (cohort)	Percentage of participants alive at 2 years post start of treatment.
Overall Survival (OS)	Up to 5 years (cohort)	Mean number of months patients remain alive from the day of trial enrollment until either an death from any cause or last follow-up.