Neo-adjuvant SABR for IVC Tumor Thrombus in Newly Diagnosed RCC

• ClinicalTrials.gov Identifier: NCT02473536
• Recruitment Status: Recruiting
• First Posted: June 16, 2015
• Last Update Posted: March 8, 2021
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Raquibul Hannan, University of Texas Southwestern Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Radiation: Stereotactic ablative radiation therapy	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: 6 for Lead-in phase; 23 for phase II
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety Lead-in Phase II Trial of Neo-adjuvant SABR for IVC Tumor Thrombus in Newly Diagnosed RCC
• Actual Study Start Date: June 2015
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Stereotactic ablative radiation therapy; SABR	Radiation: Stereotactic ablative radiation therapy; SABR

Outcome Measures

Primary Outcome Measures :

1. To determine the feasibility of neoadjuvant SABR followed immediately by IVC tumor thrombectomy [ Time Frame: 90 days ]
   The treatment duration will be between 2-3 weeks depending on the fraction scheme chosen.
2. To determine the operative safety of neoadjuvant SABR followed immediately by IVC tumor thrombectomy [ Time Frame: 90 days ]
   The treatment duration will be between 2-3 weeks depending on the fraction scheme chosen.
3. Survival at one year [ Time Frame: ONE YEAR ]
   Phase II To determine the relapse-free survival at one-year

Secondary Outcome Measures :

1. Peri-operative morbidity [ Time Frame: 90 days ]
   To describe the associated peri-operative morbidity. Associated peri-operative morbidity is defined as grade>2 side effects as assessed by NCI's CTCAE v4.0 toxicity within one year of surgery.
2. Adverse events post surgery [ Time Frame: 1 year ]
   To determine the associated adverse events within one year of surgery. Associated adverse events are any toxicity as defined by NCI's CTCAE v4.0 toxicity criteria for the first year post- surgery.
3. Recurrence free survival (1 year) [ Time Frame: 1 year ]
   To determine the 1 year recurrence free survival
4. Recurrence free survival overall [ Time Frame: 5 years ]
   To determine the recurrence free survival
5. Recurrence [ Time Frame: 5 years ]
   To determine the median time to recurrence
6. Pulmonary emboli [ Time Frame: 1 year ]
   To determine the rate of pulmonary emboli within one year of surgery. Pulmonary Emboli: Pulmonary embolus determined in patients that become symptomatic and as a result has radiographic evidence of pulmonary embolus on CT angio or V/Q scan.
7. Pulmonary metastasis [ Time Frame: 5 years ]

   To determine the rate of pulmonary metastasis. Pulmonary Metastasis: Any evidence of new lung metastasis >1.0 cm

   • New lung nodules >0.5cm will also be reported.

8. Systemic metastasis [ Time Frame: 5 years ]
   To determine the rate of systemic metastasis. Systemic Metastasis: Any evidence of new metastasis that is progressing on a second scan > 6 weeks apart
9. Overall survival [ Time Frame: 5 years ]
   The rate of overall survival. Overall Survival: Time to death from the date of treatment start.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Sandra Morones; 2146458525; Sandra.Morones@UTSouthwestern.edu

Contact: Sarah Hardee; 2146458525; sarah.hardee@utsouthwestern.edu

Locations

United States, Texas

University of Texas Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75239

Contact: Raquibul Hannan, MD 214-645-8525

Contact: Sarah Hardee, MS 2146458525 Sarah.Hardee@UTSouthwestern.edu

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Raquibul Hannan, MD; UTSW

More Information

• Responsible Party: Raquibul Hannan, Associate Professor of Medicine, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT02473536
• Other Study ID Numbers: STU 022015-058
• First Posted: June 16, 2015
• Last Update Posted: March 8, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Carcinoma, Renal Cell; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases