Clinical trial NCT06265285: Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program
Official title: Pilot Single-Arm, Pragmatic Trial of In-Home Versus In-Clinic Subcutaneous Nivolumab Administration Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Esophageal Squamous Cell Carcinoma
Advanced Renal Cell Carcinoma
Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8
Clinical Stage IIB Cutaneous Melanoma AJCC v8
Clinical Stage IIC Cutaneous Melanoma AJCC v8
Clinical Stage III Cutaneous Melanoma AJCC v8
Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8
Clinical Stage IV Cutaneous Melanoma AJCC v8
Clinical Stage IV Esophageal Squamous Cell Carcinoma AJCC v8
Esophageal Carcinoma
Gastroesophageal Junction Adenocarcinoma
Hepatocellular Carcinoma
Locally Advanced Urothelial Carcinoma
Lung Non-Small Cell Carcinoma
Malignant Solid Neoplasm
Metastatic Colorectal Carcinoma
Metastatic Cutaneous Melanoma
Metastatic Esophageal Squamous Cell Carcinoma
Metastatic Head and Neck Squamous Cell Carcinoma
Metastatic Urothelial Carcinoma
Recurrent Esophageal Squamous Cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Renal Cell Carcinoma
Stage III Renal Cell Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Stage IV Renal Cell Cancer AJCC v8
Unresectable Cutaneous Melanoma
Unresectable Esophageal Squamous Cell Carcinoma
Urothelial Carcinoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial compares the impact of subcutaneous (SC) nivolumab given in an in-home setting to an in-clinic setting on cancer care and quality of life. Currently, most drug-related cancer care is conducted in clinic type centers or hospitals which may isolate patients from family, friends and familiar surroundings for many hours per day. This separation adds to the physical, emotional, social, and financial burden for patients and their families. Traveling to and from medical facilities costs time, money, and effort and can be a disadvantage to patients living in rural areas, those with low incomes or poor access to transport. Studies have shown that cancer patients often feel more comfortable and secure being cared for in their own home environments. SC nivolumab in-home treatment may be safe, tolerable and/or effective when compared to in-clinic treatment and may reduce the burden of cancer and improve the quality of life in cancer patients.

Detailed description: PRIMARY OBJECTIVE:

I. Determine the change in patient-reported rating of Cancer Connected Access and Remote Expertise (CARE) after 8 weeks in clinic compared to the same rating after 8 weeks at home.

SECONDARY OBJECTIVES:

I. Evaluate patient preference for location of cancer treatment administration, in the clinic or in the home.

II. Longitudinally assess patient-reported function and global health/quality of life.

III. Longitudinally assess patient-reported symptoms. IV. Assess the safety of cancer directed therapy when administered at home by a home health provider with remote patient monitoring and command center support.

V. Describe emergency room visits and hospitalizations over the course of the study.

VI. Describe overall survival (data collected out to 1 year).

TERTIARY OBJECTIVE:

I. Assess the cost outcomes related to patient treatment in the clinic or in the home.

OUTLINE:

Patients receive nivolumab SC on day 1 of each cycle. Cycles repeat every 28 days in clinic for 2 cycles, then at home by a home health nursing provider (HHNP) for 4 cycles, followed by either in-clinic or at-home administration for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive in-home visits by a home health nurse, undergo remote patient monitoring including vital sign measurements and condition-specific symptom assessments throughout study.

After completion of study treatment, patients are followed up at days 30 and 100, then every 3 months for up to 1 year.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Histologically confirmed malignancies for which treatment with intravenous nivolumab is currently Food and Drug Administration (FDA) approved and who are recommended to initiate a new treatment regimen with single agent intravenous (IV) nivolumab by their treating oncologist for any of the indications outlined below and who are willing to switch to subcutaneous nivolumab:

  * Single agent nivolumab administered in the adjuvant setting for one of the following indications:

    * Completely resected stage IIB/C, III or IV melanoma
    * Urothelial carcinoma status post radical resection and have a high risk of recurrence
    * Completely resected esophageal or gastroesophageal junction carcinoma with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT)
  * Single agent nivolumab for advanced/metastatic cancer for one or more of the following indications:

    * Renal cell carcinoma (RCC) patients who have received prior anti-angiogenic therapy
    * Non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (Note: patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab)
    * Unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy
    * Unresectable or metastatic cutaneous melanoma
    * Locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
    * Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy
    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
  * Patients transitioning to maintenance nivolumab and who are willing to switch to subcutaneous nivolumab after completion of Ipilimumab and nivolumab combination therapy for one or more of the indications listed below (Note: patients who discontinue ipilimumab for immune-related toxicities, but are deemed to be eligible to continue on single agent nivolumab maintenance by their treating oncologist are eligible):

    * First-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC)
    * Unresectable or metastatic cutaneous melanoma
    * Hepatocellular carcinoma (HCC) previously treated with sorafenib
    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
* Patients have recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (i.e., residual toxicity no worse than grade 1 \[grade 2 treatment-associated peripheral neuropathy, grade 2 fatigue and/or any grade of alopecia are acceptable assuming all other inclusion criteria are met\]) before registration
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Aspartate transaminase (AST) values ≤ 3 × the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase
* Alanine transaminase (ALT) values ≤ 3 x the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 x ULN for transaminase
* Serum total bilirubin values of ≤ 1.5 x ULN ( ≤ 2 x ULN for patients with known Gilbert's syndrome). For patients with documented baseline liver metastasis, the following limits will apply: 2 x ULN for bilirubin
* Absolute neutrophil count (ANC) of ≥ 1500/μL
* Platelet count of ≥ 100,000/μL
* Hemoglobin of ≥ 9 g/dL (patients may be transfused to this level, if necessary, but transfusion must occur \> 1 week prior to registration)
* Serum creatinine ≤ 2.0 x the ULN for the reference laboratory or a calculated creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault Equation measured ≤ 7 days prior to registration
* Patients are residing ≤ 35 miles of clinic (hub) or within the area serviced by supplier and paramedic network
* Residence has Wi-Fi to enable a reliable connection with the remote command center
* Patients have signed Informed Consent Form (ICF)
* Patients are willing and able to comply with the study protocol in the investigator's judgment
* Patients are able and willing to complete study questionnaire(s) by themselves or with assistance
* Women of childbearing potential (WOCBP) must:

  * Have a negative pregnancy test (serum or urine) ≤ 3 days before the first dose of study drug
  * Be agreeable to use a contraceptive method that is highly effective during the intervention period and for at least 5 months after the last dose and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time period

Exclusion Criteria:

* Patients receiving any other investigational or standard of care agent which would be considered as a treatment for the primary neoplasm and is not part of the eligible treatment regimen
* Patients requiring 24/7 assistance with activities of daily living (ADLs)
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Uncontrolled intercurrent illness including, but not limited to:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Myocardial infarction ≤ 6 months
  * Wound healing disorder
  * Psychiatric illness/social situations that would limit compliance with study requirements
* Patients with any severe infection ≤ 4 weeks prior to registration including, but not limited to, hospitalization for complications of infections
* Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded
* Patients with a condition requiring systemic treatment with either corticosteroids ( \> 10 mg daily prednisone equivalent) ≤ 14 days or other immunosuppressive medications ≤ 30 days prior to registration. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active ≤ 2 years prior to registration (i.e., participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before randomization/treatment assignment and the patient has no evidence of disease). Participants with history of prior early stage basal/squamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible
* Patients have undergone prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant
* Patients with active brain metastases or leptomeningeal metastases, aside from the exceptions below. Participants with brain metastases are eligible if they are:

  * Asymptomatic
  * Have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the central nervous system \[CNS\] treatment), and
  * There is no MRI evidence of progression for at least 4 weeks after CNS directed therapy is complete and ≤ 28 days prior to registration
  * In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to registration
* Participants with brain disease treated with whole brain radiation
* Anticipation of the need for major surgery during the course of study treatment
* Participants who are pregnant or breastfeeding
* Treatment with any live attenuated vaccines ≤ 30 days of registration (vaccines that are not live attenuated are allowed, including COVID-19 vaccine)
* Known human deficiency virus (HIV) positive with an AIDS defining opportunistic infection within the last year, or a current CD4 count \< 350 cells/uL, aside from the exceptions below. Participants with HIV are eligible if:

  * They have received antiviral therapy (ART) for at least 4 weeks prior to treatment assignment as clinically indicated while enrolled in the study
  * They continue on ART as clinically indicated while enrolled on study
  * CD4 counts and viral load are monitored per standard of care by a local healthcare provider
* History of allergy or hypersensitivity to study drug components
* Any positive test result for hepatitis B virus (HBV) indicating presence of virus (e.g., hepatitis B surface antigen \[HBsAg, Australia antigen\]) positive
* Any positive test result for hepatitis C virus (HCV) indicating presence of active viral replication (detectable HCV-ribonucleic acid \[RNA\]). Note: Participants with positive HCV antibody and an undetectable HCV RNA are eligible to enroll

Primary outcomes:
measure: Change in patient-reported rating of Cancer CARE Cancer Connected Access and Remote Expertise (CARE) after 8 weeks
timeFrame: At baseline and up to 24 weeks of in clinic or at home care
Secondary outcomes:
measure: Patient preferred treatment location
timeFrame: Up to 24 weeks
measure: Patient level of comfort with receiving injections at home
timeFrame: Up to 24 weeks
measure: Patient-reported symptoms - PRO-CTCAE
timeFrame: Up to 24 weeks
measure: Patient-reported function - EORTC QLQ-F17
timeFrame: Baseline; 8 weeks; 16 weeks; 24 weeks
measure: Patient-reported side effect impact - GP5
timeFrame: After 8 weeks of in-clinic and 8 weeks of at home care
measure: Incidence of Adverse Events (AEs)
timeFrame: At 8 weeks of in-clinic and 8 weeks at home care
measure: Emergency room visits and hospitalizations
timeFrame: At 8 weeks of in-clinic and at 8 weeks of at home care
measure: Overall survival (OS)
timeFrame: Up to one year post study completion
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Roxana S. Dronca, M.D.
role: PRINCIPAL_INVESTIGATOR
References: