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

May 20, 2026 updated by: Rajat Thawani, OHSU Knight Cancer Institute

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • OHSU Knight Cancer Institute
        • Contact:
        • Principal Investigator:
          • Rajat Thawani

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (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.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Immune Checkpoint Inhibitor
Receive immune checkpoint inhibitor therapy
Other Names:
  • ICI
Experimental: Treatment (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.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Immune Checkpoint Inhibitor
Receive immune checkpoint inhibitor therapy
Other Names:
  • ICI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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])
The associated 95% confidence interval (CI) for each treatment group will be estimated using the Kaplan-Meier method. The stratified hazard ratio (HR) and its 95% CI will be estimated using a Cox proportional-hazard model with treatment group as the independent variable and stratified by the same randomization stratification factors as were used for the log-rank test.
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

Outcome Measure
Measure Description
Time Frame
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
The median duration of OS and the associated 95% CI for each treatment group will be estimated using the Kaplan-Meier method. The stratified HR and its 95% CI will be estimated using a Cox proportional-hazard model with treatment group as the independent variable and stratified by the same randomization stratification factors as were used for the log-rank test.
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).
Will be analyzed for all evaluable patients using a Kaplan-Meyer survival analysis. The number of events, percentiles for the time to discontinuation for irAE-related reasons (25%, 50% (median), and 75% percentiles), and the proportion of participants who discontinued standard-of-care for irAE-related reasons will be summarized by treatment group.
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OHSU Knight Cancer Institute

Collaborators

Oregon Health and Science University

Investigators

  • Principal Investigator: Rajat Thawani, OHSU Knight Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 31, 2026

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

February 4, 2026

First Submitted That Met QC Criteria

February 4, 2026

First Posted (Actual)

February 12, 2026

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00029305 (Other Identifier: OHSU Knight Cancer Institute)
  • NCI-2026-00433 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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