Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study

Official title

Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study

Overview

This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.

Detailed description

PRIMARY OBJECTIVE:

I. To compare progression-free survival among participants receiving immunotherapy based on time of day (ToD) administration (early versus \[vs.\] late).

SECONDARY OBJECTIVES:

I. To compare overall survival among participants receiving immunotherapy based on ToD administration (am vs. pm).

II. To compare rates of significant immune-related adverse events (irAEs) based on ToD administration (am vs. pm).

EXPLORATORY OBJECTIVES:

I. To compare objective responses among participants receiving immunotherapy based on ToD administration (am vs. pm).

II. To compare disease control among participants receiving immunotherapy based on ToD administration (am vs. pm).

III. To compare the duration of response among participants receiving immunotherapy based on ToD administration (am vs. pm).

OUTLINE: Patients are randomized to 1 of 2 cohorts.

AM COHORT: Patients receive standard of care immunotherapy before 10:30 for 4 doses in the absence of disease progression or unacceptable toxicity. Subsequent doses may be given per standard of care timing. Patients also undergo blood sample collection throughout the study.

PM COHORT: Patients receive standard of care immunotherapy after 13:30 for 4 doses in the absence of disease progression or unacceptable toxicity. Subsequent doses may be given per standard of care timing. Patients also undergo blood sample collection throughout the study.

After completion of immunotherapy treatment, patients are followed up every 6 months for 2 years.

Interventions

• Procedure Biospecimen Collection
  Undergo blood sample collection
• Drug Immune Checkpoint Inhibitor
  Receive immune checkpoint inhibitor therapy

Primary outcome measures

• Progression free survival [Time frame: From date of randomization to date of first progression or death (any cause), whichever occurs first (up to 2 years from date of last dose of standard-of-care immune checkpoint inhibitor [ICI])]

Secondary outcome measures (2)

• Overall survival (OS) [Time frame: From date of randomization to date of death (any cause) up to 2 years from date of last dose of standard-of-care ICI]
• Incidence of immune related adverse event (irAE) related time to treatment discontinuation [Time frame: From date of first dose of standard-of-care ICI to date of last dose of standard-of-care ICI (an average of 2 years).]

Eligibility criteria

Inclusion criteria

• Must provide written informed consent before any study-specific procedures or interventions are performed
• Aged ≥ 18 years
• Histologically confirmed advanced/metastatic solid tumor as follows:

• Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \[ICI\]-eligible)
• Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),
• Renal cell carcinoma (RCC)
• Biliary-tract cancer (BTC)
• Hepatocellular carcinoma (HCC)
• Melanoma
• Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Exclusion criteria

• Prior ICI-based regimen for treatment of cancer
• Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg/day of prednisone (or equivalent corticosteroid)
• Uncontrolled autoimmune disease requiring immunosuppression
• Active, uncontrolled central nervous system (CNS) metastases

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• OHSU Knight Cancer Institute — Portland

Identifiers

NCT: NCT07405086 · STUDY00029305 · NCI-2026-00433 · STUDY00029305

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗