Morning versus afternoon immunotherapy for advanced or metastatic solid tumors
Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study
This trial tests whether giving standard immune checkpoint inhibitor therapy in the morning versus the afternoon changes outcomes for adults with advanced or metastatic solid tumors.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 160 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | OHSU Knight Cancer Institute Academic / other |
| Drugs / interventions | immunotherapy, prednisone |
| Locations | 1 site (Portland, Oregon) |
| Trial ID | NCT07405086 on ClinicalTrials.gov |
What this trial studies
This randomized phase IV trial assigns adults with advanced or metastatic solid tumors to receive standard-of-care immune checkpoint inhibitors either before 10:30 AM or after 1:30 PM for the first four doses, with subsequent dosing per usual care. The primary endpoint is progression-free survival, with overall survival and rates of significant immune-related adverse events as key secondary endpoints and objective response, disease control, and duration of response as exploratory endpoints. Blood samples are collected during treatment to study immune and circadian biomarkers that might explain any timing effects. After completing immunotherapy, participants are followed every six months.
Who should consider this trial
Good fit: Adults (≥18) with measurable advanced or metastatic solid tumors such as driver‑negative, ICI‑eligible NSCLC, recurrent/metastatic HNSCC, renal cell carcinoma, biliary tract cancer, hepatocellular carcinoma, or melanoma who are about to start an FDA‑approved immune checkpoint inhibitor and have not previously received ICI therapy.
Not a fit: Patients who have previously received immune checkpoint inhibitors, who require immediate targeted therapy for actionable driver mutations, or who need ongoing immunosuppression are unlikely to benefit from changing infusion timing.
Why it matters
Potential benefit: If successful, a simple change in dosing time could improve cancer control or reduce immune-related side effects without changing the medications used.
How similar studies have performed: This circadian‑timing approach is relatively novel: small observational and exploratory studies have suggested time‑of‑day effects on immune responses, but large randomized confirmations are not yet established.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Portland, Oregon
- OHSU Knight Cancer Institute — Portland, Oregon, United States (Recruiting)
Study contacts
- Principal investigator: Rajat Thawani — OHSU Knight Cancer Institute
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.