Controlled Cold Exposure Combined With PD-1/PD-L1 Immunotherapy in Solid Tumors (NIVALIS)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorWest China Hospital
About this trial
This is a single-center, prospective, single-arm, open-label phase I exploratory study that plans to enroll 24 participants with solid malignancies. All participants will receive controlled cold exposure in addition to standard PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor-based standard combination therapy. A 2-day cold acclimation phase will precede formal intervention, consisting of approximately 20°C exposure for 8 hours on Day -2 and approximately 18°C exposure for 10 hours on Day -1. The first combination cycle begins on Day 1 concurrently with PD-1/PD-L1-based treatment, with exposure to an 18°C temperature-controlled hospital room for 12 hours per day for 7 consecutive days. If tolerated, cold exposure may be repeated in subsequent PD-1/PD-L1 treatment cycles. The primary objective is to evaluate safety, tolerability, and feasibility. Secondary objectives are to explore preliminary antitumor activity and the effects on brown adipose tissue activation, peripheral immune profiling, circulating cytokines, metabolomics, gut microbiota, patient-reported outcomes, and tumor immune/metabolic biomarkers when paired tumor tissue is available.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1. Age 18-75 years, regardless of sex. 2. Histologically or cytologically confirmed malignant solid tumor. 3. Evaluated by the treating physician or multidisciplinary team (MDT) as currently planned to receive standard PD-1/PD-L1 inhibitor monotherapy or a standard combination regimen containing PD-1/PD-L1 inhibitors.
Disqualifiers
1. Participation in another interventional clinical study or receipt of another investigational treatment within 4 weeks before study treatment initiation.
Trial design
Design model
Single group
Treatments tested in this trial
Controlled Cold Exposure
Other interventionControlled environmental cold exposure in a temperature-controlled hospital room. Cold acclimation includes approximately 20°C for 8 hours on Day -2 and approximately 18°C for 10 hours on Day -1; formal intervention consists of 18°C exposure for 12 hours per day for 7 consecutive days and may be repeated in later cycles if tolerated.
Investigator-Selected Standard PD-1/PD-L1 Inhibitor-Based Therapy
DrugStandard PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor-containing standard combination therapy selected according to tumor type, clinical guidelines, and routine clinical practice.
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: Experimental: Controlled Cold Exposure + Standard PD-1/PD-L1-Based TherapyExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence of Adverse Events, Serious Adverse Events, and Safety-Related Treatment Modifications
The safety of the study treatment will be evaluated by recording adverse events (AEs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), immune-related adverse events (irAEs), grade 3-4 TEAEs, and interruptions, delays, or discontinuations of controlled cold exposure or immunotherapy due to adverse events. Results will be reported as the proportion of participants experiencing the corresponding events (%) and the number of events.
Time frame
From the start of the first study-related intervention until 30 days after the last protocol-specified treatment or the initiation of a new anticancer therapy, whichever occurs first.2
Completion Rate and Adherence to Controlled Cold Exposure
The feasibility of the controlled cold exposure intervention will be evaluated by assessing the completion rate of planned cold exposure, intervention adherence, early withdrawal rate, and interruptions or discontinuations of cold exposure due to intolerance. Results will be reported separately as proportions (%).
Time frame
Primarily assessed during the first combined intervention cycle (Day 1 to Day 7), and continuously recorded until completion of the last protocol-specified cold exposure treatment.Secondary outcomes
1
Objective Response Rate
Objective response rate is defined as the proportion (%) of participants with evaluable or measurable lesions who achieve a complete response (CR) or partial response (PR) according to RECIST 1.1.
Time frame
The first imaging assessment will be performed 6-8 weeks after treatment initiation, and subsequently every 8-12 weeks until disease progression, withdrawal from the study, or study completion, up to 12 months.2
Disease Control Rate
Disease control rate is defined as the proportion (%) of participants with evaluable or measurable lesions who achieve complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.
Time frame
The first imaging assessment will be performed 6-8 weeks after treatment initiation, and subsequently every 8-12 weeks until disease progression, withdrawal from the study, or study completion, up to 12 months.3
Progression-Free Survival
Progression-free survival will be defined as the time from the start of the first study-related intervention to documented disease progression or death from any cause, whichever occurs first.
Time frame
From the start of the first study-related intervention until study completion, up to 36 months.4
Overall Survival
Overall survival will be defined as the time from the start of the first study-related intervention to death from any cause.
Time frame
From the start of the first study-related intervention until study completion, up to 36 months.Sponsors and contacts
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Source ClinicalTrials.gov