SAbR For Oligometastatic Renal Cell Carcinoma

Oligometastatic Renal Cell Carcinoma Clinical Trial

Official title:

Phase II Trial of SAbR for Patients With Oligometastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02956798
• Other study ID #: STU 042016-046
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 19, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hypothesis:

Stereotactic ablative body radiation (SAbR) prolongs progression-free survival for patients with oligometastatic kidney cancer (RCC) and delays the initiation of systemic therapy.

Primary Objectives:

• To evaluate the delay in time to start of systemic therapy (TTST) as a surrogate of progression free survival (PFS), defined as the time from the first day of SAbR to start of systemic therapy.

Secondary Objective:

• To evaluate the modified progression-free survival (mPFS) for patients with oligometastatic renal cell carcinoma who are treated with SAbR.

• To evaluate the overall survival (OS)

• To evaluate the cancer specific survival (CSS)

• To evaluate the local control rate of irradiated lesions.

• To measure the health-related quality of life (HRQOL).

Description:

The study is a prospective single institution phase II single-arm open-label trial evaluating SAbR in patients with newly diagnosed oligometastatic RCC.

Problem Statements:

• Can local therapy (SAbR) safely delay the start of systemic therapy?

• Safely delaying the start of systemic therapy can have significant quality of life benefits for patients since systemic therapy has significant side effects.

• Can SAbR be curative in truly oligometastatic RCC patients?

Primary Endpoint:

• Time to start of systemic therapy (TTST) defined as the time from the first day of SAbR to start of systemic therapy.

Secondary Endpoint:

• Modified progression-free survival (mPFS) is defined as the survival interval without development of >3 sites of new metastasis, new sites of metastases that are not amenable to SAbR treatment, a total of >6 sites of metastasis that required SAbR, local failure at SAbR-treated site, or development of brain metastasis.

• Overall Survival

• Local control

• Toxicity

• HRQOL

Sample Size: 23 Patients will be enrolled.

Statistical Analysis: Time to event will be estimated using the Kaplan-Meier approach along with the 95% confidence interval.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Metastatic renal cell carcinoma with limited measurable extracranial metastases (Limited metastases, or oligometastases, defined as =3 sites of metastasis).

• Radiographic evidence of metastatic disease. CT should be performed within 30 days of registration.

• Pathology confirmation of Renal cell carcinoma.

• Prior surgery, or radiation is permitted.

• Age = 18 years.

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and for 90 days after Radiation treatment has been completed . Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

A female of child-bearing potential is any woman (regardless of sexual orientation, 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).

• Ability to understand and the willingness to sign a written informed consent and agrees to undergo image studies and follow up

Exclusion Criteria:

• Subjects with brain metastasis as assessed by contrast MRI or contrast CT scans(contrast recommended).

• Subjects with previous history of brain metastasis.

• Subjects that received prior systemic therapy for kidney cancer in the past 1 year, except one line of immuno- or cytokine therapy (e.g. prior IL-2); systemic therapy for other cancers does not apply to this exclusion criteria

• Subjects with =3 unfavorable prognostic factors defined by Motzer et al. (1999), (KPS <80% or ECOG>1, Hgb < LLN, LDH >1.5x normal, corrected serum calcium >10mg/dl and absence of prior nephrectomy), Patients with 0, 1-2, and =3 factors had time to death of 20 months, 10 months and 4 months.

• Subjects with life expectancy < 6 months.

• Subjects receiving any other investigational agents

• Subjects must not be pregnant due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Oligometastatic Renal Cell Carcinoma

Intervention

Radiation:
• Stereotactic ablative body radiation (SABR)
SAbR treatment regimens including =25Gy x1 fraction, =12Gy x 3 fractions, or =8Gy x 5 fractions.

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to start of systemic therapy (TTST)	To evaluate the delay in time to start of systemic therapy (TTST) as a surrogate of progression free survival (PFS), defined as the time from the first day of SAbR to start of systemic therapy.	1 Year
Secondary	Modified progression-free survival (mPFS) for patients who are treated with SAbR	Modified progression-free survival (mPFS) for patients with oligometastatic renal cell carcinoma who are treated with SAbR. Modified progression-free survival (mPFS) is defined as the survival interval without development of >3 sites of new metastasis, new sites of metastases that are not amenable to SAbR treatment, a total of >6 sites of metastasis that required SAbR, local failure at SAbR-treated site, or development of brain metastasis, with the definition of new metastasis and local failure (progression) as defined by RECIST. "Metastasis" in this entire protocol refers to extra-cranial metastasis unless otherwise specified.	6 years
Secondary	Progression-free survival on systemic therapy (mPFS)	To evaluate progression on next line of systemic therapy as defined by RECIST 1.1 starting from mPFS (modified progression free survival). Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) Committee [Eur J Cancer. 2009;45(2):228-247]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST v1.1 criteria.	6 years
Secondary	Overall survival (OS)	Overall survival (OS), which is defined as the time between date of registration and the date of death due to any cause.	6 years
Secondary	Cancer specific survival (CSS)	Cancer specific survival is defined as the time between date of registration and the date of death due to renal cell carcinoma.	6 years
Secondary	Local Control	Radiographic progression with >30% increase in the longest diameter of the treated lesions.	6 years
Secondary	Median response duration	Median response duration is defined as the time between the date a response (CR or PR) was first seen until date of progression. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) Committee [Eur J Cancer. 2009;45(2):228-247]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST v1.1 criteria.	6 years
Secondary	Time to development of new lesions	Interval time to development of new lesions that can be treated with additional local therapy- title would be this or a shortened version of it. Time to event will be estimated using the Kaplan-Meier approach along with the 95% confidence interval.	6 years
Secondary	Time to disease progression that cannot be treated	To measure the time interval from registration to time to disease progression that cannot be treated with further local therapy and need to initiate or switch systemic therapy. Time to event will be estimated using the Kaplan-Meier approach along with the 95% confidence interval.	6 years
Secondary	Acute & Delayed Toxicity	Severity or Toxicity will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. Dose adjustments should be made according to the system showing the greatest degree of toxicity. The consequences of toxicity should all be graded 1-5 according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 occurring prior to 270 days from the start of protocol treatment. Other treatment related toxicity attributed to the therapy will be captured, recorded and the consequences of should all be graded 1-5 according to the Common Terminology Criteria for Adverse Events (CTCAE). CTCAE V5.0 along with grades 1-5.	6 years
Secondary	Health-related quality of life (HRQOL) FACT-G	HRQOL will be measured using FACT-G questionnaire at baseline and at first follow up 8-12 weeks (+/- 4 weeks) then 12 week (±4 week) intervals for 1 year, and every 26 weeks (±4 weeks) until the completion of follow ups. FACT-G is a measure that sums the functional well being (FWB), physical well being (PWB), the social/family well-being (S/FWB), and emotional well being (EMB).	6 years
Secondary	Health-related quality of life (HRQOL) EQ-5D	HRQOL will be measured using EQ-5D (EuroQol- 5 Dimension) questionnaire at baseline and at first follow up 8-12 weeks (+/- 4 weeks) then 12 week (±4 week) intervals for 1 year, and every 26 weeks (±4 weeks) until the completion of follow ups. EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.	6 years
Secondary	Health-related quality of life (HRQOL) FKSI	HRQOL will be measured using FKSI questionnaire at baseline and at first follow up 8-12 weeks (+/- 4 weeks) then 12 week (±4 week) intervals for 1 year, and every 26 weeks (±4 weeks) until the completion of follow ups. FKSI adds to the FACT-G (27 items) by including 15 items specific to kidney cancer patients. In a HRQOL study focused on patient with mRCC, a symptoms subscale questionnaire was developed and will also be administered in this study.	6 years
Secondary	Health-related quality of life (HRQOL) cost-effectiveness	Health care utilization data needed to assess costs will be obtained from the cost & convenience questionnaire, which includes costs of hospitalization, treatment, ER visits, physician and clinic visits and medications. Markov modeling with probabilistic sensitivity analysis will be used to correlate quality-adjusted survival and cost. Cost-effective analysis (cost & convenience questionnaire) will be given prior to treatment and at the time of progression.	6 years