Clinical trial NCT02473536: Neo-adjuvant SABR for IVC Tumor Thrombus in Newly Diagnosed RCC
Official title: Safety Lead-in Phase II Trial of Neo-adjuvant SABR for IVC Tumor Thrombus in Newly Diagnosed RCC
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Renal Cell Carcinoma
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2015-06-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 6 for Lead-in phase; 23 for phase II
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and feasibility of pre-operative SABR of RCC IVC tumor thrombus.

To evaluate the effect of pre-operative SABR in RCC IVC tumor thrombus on relapse free survival at one year.

Detailed description: Stereotactic Ablative Radiation Therapy (SABR): 5 fractions of 8 Gy or 3 fractions of 12Gy. The concept of stereotactic radiosurgery involves tightly conforming dose of therapeutic radiation confined to a small region of the body. This results in eradication or ablation of the target tumor with sparing of surrounding normal tissues. The largest experience with stereotactic radiosurgery is for the treatment of intracranial tumors Neoadjuvant treatment of IVC-TT with SABR may decrease local recurrences and lower the likelihood of embolic complications and systemic metastasis.

Eligibility criteria: Inclusion Criteria:

1. Radiographic evidence of renal cancer with IVC tumor thrombus
2. Tumor thrombus must be ≥ level II (As per Mayo classification, it would be ≥ level I \[Refer to NEVES, R. and ZINCKE, H. (1987), Surgical Treatment of Renal Cancer with Vena Cava Extension. British Journal of Urology, 59: 390-395. doi:10.1111/j.1464-410X.1987.tb04832.x\])
3. Patient eligible for SABR to the IVC tumor thrombus as decided by the treating radiation oncologist
4. Patient eligible for IVC tumor thrombectomy as decided by the treating urologist
5. Any number of metastatic disease is allowed in the Pilot phase of the trial

   • For Phase II, metastatic patients will be allowed only if all sites of metastasis has been treated either surgically or radio-surgically (If limited sites of metastasis are present, all of which can be resected during the nephrectomy, then the patient can be eligible)
6. Age ≥ 18 years.
7. Performance status ECOG 0-2
8. Any serum Albumin is allowed, but ≥ 3.4 g/dL is strongly encouraged

   • Serum albumin \<3.4 is a significant predictor of peri-operative mortality(12)
9. Any serum AST is allowed but serum AST ≤ 34 IU/L is strongly encouraged

   • Significant predictor of mortality in univariate but not multivariate analysis(12)
10. Women of childbearing potential and men must agree to use adequate contraception (hormonal such as birth control pills, patch or ring; Depo-Provera, Implanon or barrier method, such as condom or diaphragm used with a spermicide of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 90 days following completion of radiation therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

    10.1 A female of childbearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
    * Has not undergone a hysterectomy or bilateral oophorectomy; or
    * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
11. Ability to understand and the willingness to sign a written informed consent.
12. Subjects must be able to undergo either MRI or CT.

Exclusion Criteria:

1. Subjects who have had radiotherapy to a target within 3 cm of the IVC tumor thrombus.
2. Subjects may have received any other investigational agents or chemotherapy as long as they are eligible for SABR and surgery
3. Subjects with brain metastases should be excluded from this clinical trial unless all the metastasis are treated surgically or radio-surgically
4. Subjects with a history of pulmonary embolism is excluded
5. Subjects with a history of pulmonary hypertension is excluded
6. Subjects must not be pregnant due to the potential for congenital abnormalities.
7. Contraindication for contrast-enhanced MRI as defined by the standard operating procedures of the Department of Radiology at UT Southwestern. Briefly, these include medically unstable; cardiac pacemaker; intracranial clips, metal implants; metal in the eyes; pregnant or nursing; claustrophobia; and impairment of the renal function with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2. Patients with one or more of these contraindications but eligible to undergo contrast-enhanced CT can participate in this study and will not receive an MRI

Primary outcomes:
measure: To determine the feasibility of neoadjuvant SABR followed immediately by IVC tumor thrombectomy
timeFrame: 90 days
measure: To determine the operative safety of neoadjuvant SABR followed immediately by IVC tumor thrombectomy
timeFrame: 90 days
measure: Survival at one year
timeFrame: ONE YEAR
Secondary outcomes:
measure: Peri-operative morbidity
timeFrame: 90 days
measure: Adverse events post surgery
timeFrame: 1 year
measure: Recurrence free survival (1 year)
timeFrame: 1 year
measure: Recurrence free survival overall
timeFrame: 7 years
measure: Recurrence
timeFrame: 7 years
measure: Pulmonary emboli
timeFrame: 1 year
measure: Pulmonary metastasis
timeFrame: 7 years
measure: Systemic metastasis
timeFrame: 7 years
measure: Overall survival
timeFrame: 7 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: UTSW
name: Raquibul Hannan, MD
role: PRINCIPAL_INVESTIGATOR
References: