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SAbR For Oligometastatic Renal Cell Carcinoma

Primary Purpose

Oligometastatic Renal Cell Carcinoma

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Stereotactic ablative body radiation (SABR)

About this trial

This is an interventional treatment trial for Oligometastatic Renal Cell Carcinoma focused on measuring Renal Cell, Stereotactic ablative body radiotherapy (SAbR), Pazopanib, Oligo-mets

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Stereotactic ablative body radiation (SABR)

Arm Description

Stereotactic ablative body radiation (SAbR) to all sites of measurable metastases (≤3) will be treated by SAbR. New sites of metastasis will be evaluated for continued treatment if deemed appropriate by both medical and radiation oncologists with SAbR.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

Local Control

Radiographic progression with >30% increase in the longest diameter of the treated lesions.

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.

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.

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.

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.

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).

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.

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.

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.

Full Information

NCT ID

NCT02956798

First Posted

October 26, 2016

Last Updated

July 20, 2023

Sponsor

University of Texas Southwestern Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT02956798

Brief Title

SAbR For Oligometastatic Renal Cell Carcinoma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 19, 2018 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Texas Southwestern Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief 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).

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Oligometastatic Renal Cell Carcinoma

Keywords

Renal Cell, Stereotactic ablative body radiotherapy (SAbR), Pazopanib, Oligo-mets

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Stereotactic ablative body radiation (SABR)

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Stereotactic ablative body radiation (SABR)

Intervention Description

SAbR treatment regimens including ≥25Gy x1 fraction, ≥12Gy x 3 fractions, or ≥8Gy x 5 fractions.

Primary Outcome Measure Information:

Title

Time to start of systemic therapy (TTST)

Description

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.

Time Frame

1 Year

Secondary Outcome Measure Information:

Title

Modified progression-free survival (mPFS) for patients who are treated with SAbR

Description

Time Frame

6 years

Title

Progression-free survival on systemic therapy (mPFS)

Description

Time Frame

6 years

Title

Overall survival (OS)

Description

Overall survival (OS), which is defined as the time between date of registration and the date of death due to any cause.

Time Frame

6 years

Title

Cancer specific survival (CSS)

Description

Cancer specific survival is defined as the time between date of registration and the date of death due to renal cell carcinoma.

Time Frame

6 years

Title

Local Control

Description

Radiographic progression with >30% increase in the longest diameter of the treated lesions.

Time Frame

6 years

Title

Median response duration

Description

Time Frame

6 years

Title

Time to development of new lesions

Description

Time Frame

6 years

Title

Time to disease progression that cannot be treated

Description

Time Frame

6 years

Title

Acute & Delayed Toxicity

Description

Time Frame

6 years

Title

Health-related quality of life (HRQOL) FACT-G

Description

Time Frame

6 years

Title

Health-related quality of life (HRQOL) EQ-5D

Description

Time Frame

6 years

Title

Health-related quality of life (HRQOL) FKSI

Description

Time Frame

6 years

Title

Health-related quality of life (HRQOL) cost-effectiveness

Description

Time Frame

6 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raquibul Hannan, MD, PhD

Organizational Affiliation

University of Texas

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

SAbR For Oligometastatic Renal Cell Carcinoma

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