Clinical trial NCT02781506: Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma
Official title: Phase II Trial of Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma (mRCC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Clear Cell Renal Cell Carcinoma
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2016-05-24
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Nivolumab (brand name Opdivo): IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist, until disease progression or unacceptable toxicity; SABR, dose variable, in 1-3 fractions.

Detailed description: A single institution, safety lead-in phase II trial with SAbR to multiple metastatic sites concurrently administered with Nivolumab for patients with metastatic clear cell renal cell cancer who have failed at least one anti-angiogenic therapy.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age
* Willing and able to provide consent
* Pathologic diagnosis of metastatic RCC with clear cell component
* Measurable disease in at least 2 non-radiated sites. Progression or intolerance to at least one prior systemic anti-angiogenic therapy.
* Eligible for extra-CNS SAbR to 1-6 sites of disease
* Must have received at least one prior anti-angiogenic therapy in the advanced or metastatic setting. Prior cytokine therapy (eg, IL-2, IFN-α), vaccine therapy, or treatment with cytotoxic therapy is also allowed but not any other drug specifically targeting T-cell co-stimulation or checkpoint pathways.
* Previous treatment with surgery, radiation, chemotherapy, targeted agents (see above) are allowed provided that: Chemotherapy/Major surgery was administered \> 14 days before the start Nivolumab; Minor surgery, radiation, or any targeted agents were administered \> 7 days before the start of Nivolumab
* Performance status ECOG 0, 1, 2 or 3.
* Adequate organ and marrow function as defined below (obtained within 14 days of first dose of drug):

  * leukocytes≥ 2,000/mcL
  * absolute neutrophil count ≥ 1,500/mcL
  * platelets ≥ 50,000/mcl
  * total bilirubin ≤ 2mg/dL
  * AST(SGOT)/ALT(SPGT) ≤ 3 X institutional upper limit of normal
* Women of child-bearing potential

  * 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:
  * must have a negative serum or urine pregnancy test within 24 hours prior to the start of investigational product.
  * Women must not be breastfeeding.
  * must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half lives.
  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  * Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half lives. This is equivalent to 31 weeks after discontinuation of Nivolumab.
* Adequate Renal function with Cr ≤ 2.5 mg/dL.

Exclusion Criteria:

* Subjects who have had major surgery (such as nephrectomy) or chemotherapy within 2 weeks prior to first dose of drug
* Subjects who have had radiation therapy within 2 weeks prior to first dose of drug
* Uncontrolled adrenal insufficiency or active chronic liver disease
* Any history of CNS metastases that is not adequately treated with surgery or SABR \>14 days prior.
* Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
* Any positive history for HIV/AIDS, HTLV, hepatitis B or hepatitis C virus indicating acute or chronic infection.
* Any active known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
* Subjects with life expectancy \< 6 months
* Subjects receiving any other investigational or standard antineoplastic agents.
* Prior malignancies active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, breast?, or etc.
* Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
* Patients with history of hypersensitivity to monoclonal antibodies
* Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

Primary outcomes:
measure: Response Rate (RR)
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 3 years
measure: Progression Free Survival
timeFrame: 3 years
measure: Complete Response Rate
timeFrame: 3 years
measure: Time to Progression
timeFrame: 3 years
measure: Median Response Duration
timeFrame: 3 years
measure: Median Response Duration to CR (Complete Response)
timeFrame: 3 years
measure: Adverse Events
timeFrame: 3 years
measure: Health-related Quality of Life Using FACT-G Questionnaire (Functional Assessment of Cancer Therapy-General)
timeFrame: Baseline and 6 months
measure: Health-related Quality of Life Using EQ-5D (European Quality of Life Five Dimension) Questionnaire With VAS (Visual Analogue Scale)
timeFrame: Baseline and 6 months
measure: Health-related Quality of Life Using FKSI (Functional Assessment of Cancer Therapy-Kidney Symptom Index) Questionnaire
timeFrame: Baseline and 6 months
Other outcomes:
measure: Immunological Biomarkers
timeFrame: 3 years
measure: Cost-effectiveness
timeFrame: 3 years
measure: Immunogenicity
timeFrame: 3 years
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center at Dallas
name: Raquibul Hannan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: