Clinical trial NCT03575611: Stereotactic Body Radiation Therapy in Treating Patients With Oligometastatic Renal Cell Carcinoma
Official title: Definitive Radiation-Based Treatment Strategy for Oligometastatic and Low Metastatic Burden Renal Cell Carcinoma in Lieu of Systemic Therapy
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Metastatic Renal Cell Carcinoma
Stage IV Renal Cell Cancer AJCC v8
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-07-02
Enrollment: 123
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: This phase II trial studies how well stereotactic body radiation therapy works in treating patients with kidney cancer that has spread to other places in the body (metastatic). Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the feasibility definitive radiation therapy (RT) (such as stereotactic body radiation therapy \[SBRT\]) as a treatment strategy for oligometastatic renal cell carcinoma (RCC) in lieu of systemic therapy.

II. To estimate the progression free survival (PFS) after study enrollment utilizing a strategy of definitive local treatment to all sites of disease in oligometastatic and low metastatic burden RCC as measured by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).

III. To determine the systemic therapy free survival after study enrollment

SECONDARY OBJECTIVES:

I. To determine the effect of definitive RT (SBRT) on cellular replication and death, measured by ki-67 staining and others. (Required in Cohort A, but optional in Cohort B) II. To estimate the overall survival at 12 months after study enrollment. III. To estimate the freedom from new lesion development at 12 months. IV. To determine the treatment related toxicities associated with definitive RT as part of definitive local therapy for oligometastatic and low volume metastatic RCC.

EXPLORATORY OBJECTIVE:

I. To determine the association of translational biomarkers including peripheral blood markers and tissue markers with patient outcomes.

OUTLINE:

Patients undergo SBRT over 1 day to 3 weeks based on the judgment of the treating radiation oncologist. If the disease spreads to a new lesion that can be treated with local therapy, patients may repeat SBRT over 1 day to 3 weeks based on the judgment of the treating radiation oncologist. Patients may undergo blood sample collection throughout the trial, as well as a tumor biopsy on study. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI) throughout the trial.

After completion of study treatment, patients are followed up every 12 weeks for 1 year, and then every 18 weeks thereafter.

Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed diagnosis of RCC of any histology.
* Be willing and able to undergo biopsy of a lesion planned for definitive RT (such as SBRT) both post treatment and pretreatment. If a lesion amenable to definitive RT was biopsied prior to enrollment, this material can be used in lieu of a planned biopsy if the tissue is available for review and ki-67 staining at MD Anderson.

  * Patients may be allowed on this trial without a biopsy if they are deemed medically unfit for biopsy or if the biopsy poses undue risk in the opinion of the treating physician(s).
* Be \>= 18 years of age on the day of signing informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

  * NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is considered to be ambulatory for the purpose of assessing their performance status.
* COHORT A: Oligometastatic RCC patients (=\< 5 metastatic lesions at the time of study entry).
* COHORT B: Patients eligible for Cohort A in addition to low volume metastatic patients. Low volume metastatic patients are defined as those with \> 5 metastatic lesions, but with =\< 5 metastatic lesions when excluding lesions \< 1 cm short axis and LNs \< 1 cm short axis
* Candidate for definitive local therapy to all sites of active disease per the discretion of the treating physicians
* Absolute neutrophil count (ANC) \>= 1,000 /mcL (within 6 weeks prior to study enrollment).
* Platelets \>= 50,000 / mcL (within 6 weeks prior to study enrollment).
* Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 6 weeks prior to study enrollment).
* Serum total bilirubin =\< 1.5 mg//dl (except for subjects with Gilbert syndrome, who may have total bilirubin \< 3.0 mg/dl) OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 mg/dl (within 6 weeks prior to study enrollment).
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 X upper limit of normal ULN OR =\< 5 X ULN for subjects with liver metastases (within 6 weeks prior to study enrollment).
* At least one site which in the opinion of the treating radiation oncologist is treatable with definitive RT and can be biopsied

Exclusion Criteria:

* Receipt of \> 1 line of systemic therapy directed towards the metastatic disease. This exclusion criteria will not apply for Cohort B, including the modified Cohort B definition

  * Systemic therapy as a component of prior definitive therapy directed towards non-metastatic disease will be allowed. For example, patients receiving adjuvant interleukin (IL)-2 after nephrectomy for an initial M0 diagnosis and who subsequently developed metastatic relapse will be allowed on study. In this instance, there will be no mandatory wash-out period required for enrollment.
  * At trial entry the patient must have received their last dose of systemic therapy (e.g. last intravenously \[IV\] administration of orally \[PO\] tablet/pill) 4 weeks prior to initiation of the first dose of radiation
* Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the treating physician and/or member of the study team.
* Metastatic effusion (e.g. pleural effusion or ascites). Note that patients with an effusion that is too small to sample will be eligible for the trial.
* Diffuse metastatic processes including leptomeningeal disease, diffuse bone marrow involvement, and peritoneal carcinomatous, which by the discretion of the treating physician cannot be treated definitively.
* Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit.

  * Female subject of childbearing potential should have a negative urine or serum pregnancy within 6 weeks prior to study registration up to the first fraction of radiation.
  * Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Primary outcomes:
measure: Feasibility of incorporating definitive radiation therapy (RT) (such as stereotactic body radiation therapy [SBRT]) into treatment plan for oligometastatic renal cell carcinoma (RCC) in lieu of systemic therapy
timeFrame: Up to 12 months
measure: Feasibility of incorporating definitive RT (such as SBRT) as a treatment strategy for low metastatic burden RCC in lieu of systemic therapy
timeFrame: Up to 12 months
measure: Progression-free survival (PFS) in oligometastatic RCC per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: At 12 months
measure: PFS in low metastatic burden RCC per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Up to 12 months
Secondary outcomes:
measure: Systemic therapy free survival
timeFrame: At 12 months
measure: Reduction in cellular replication as measured by ki-67 staining (Cohort A)
timeFrame: Baseline up to 12 months
measure: Overall survival
timeFrame: At 12 months
measure: Freedom from new lesion development
timeFrame: At 12 months
measure: Treatment related toxicities associated with SBRT
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Chad Tang
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang C, Msaouel P, Hara K, Choi H, Le V, Shah AY, Wang J, Jonasch E, Choi S, Nguyen QN, Das P, Prajapati S, Yu Z, Khan K, Powell S, Murthy R, Sircar K, Tannir NM. Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial. Lancet Oncol. 2021 Dec;22(12):1732-1739. doi: 10.1016/S1470-2045(21)00528-3. Epub 2021 Oct 28.