Actively Recruiting

Phase 1
Age: 18Years - 75Years
All Genders
ID07538479

Controlled Cold Exposure Combined With PD-1/PD-L1 Immunotherapy in Adults With Solid Tumors: A Single-Center, Open-Label Phase I Study to Assess Safety and Preliminary Activity

Led by West China Hospital · Updated on 2026-05-28

24

Participants Needed

1

Research Sites

100 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are exploring the safety, feasibility, and initial effectiveness of combining controlled cold exposure with standard PD-1/PD-L1 immunotherapy for adults with solid tumors. This phase I, single-center, open-label study plans to include 24 participants receiving standard immunotherapy either alone or in combination, according to routine clinical practice. The study aims to assess how cold exposure influences immune responses, tumor biomarkers, and patient outcomes alongside immunotherapy. Participants will undergo a 2-day cold acclimation before starting the combined treatment, with temperature-controlled exposure at approximately 20B0C on Day -2 and 18B0C on Day -1. From Day 1, participants will be exposed daily to 18B0C for 12 hours over 7 consecutive days while receiving their immunotherapy. If well tolerated, this cold exposure may be repeated during subsequent treatment cycles. Standard immunotherapy regimens are selected based on tumor type and clinical guidelines. During the study, researchers will monitor safety, tolerability, and adherence to the cold exposure protocol, recording adverse events from the start of the intervention until 30 days after treatment ends. They will also evaluate tumor response through imaging performed every 6-12 weeks for up to a year, and assess survival outcomes for up to 36 months. Additional assessments include immune profiling, metabolomics, gut microbiota analysis, patient-reported outcomes, and biomarker studies on tumor tissue when available. The total duration of participant involvement depends on treatment response and follow-up schedules.

CONDITIONS

Brief Title

Controlled Cold Exposure Combined With PD-1/PD-L1 Immunotherapy in Solid Tumors (NIVALIS)

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 18 and 75 years, any sex
  • Histologically or cytologically confirmed malignant solid tumor
  • Planned to receive standard PD-1/PD-L1 inhibitor monotherapy or combination therapy as per clinical guidelines
  • Treatment settings include neoadjuvant, perioperative, conversion therapy, unresectable locally advanced, recurrent, or metastatic disease
  • At least one evaluable lesion; measurable lesion required if assessed by RECIST 1.1; patients planned for surgery may be included with adequate imaging and pathology
  • ECOG performance status 0-1; ECOG 2 allowed if investigator agrees
  • Expected survival of at least 3 months
  • Adequate major organ function including hematologic, liver, kidney, and electrolytes
  • Adequate cardiopulmonary function at rest to tolerate cold exposure
  • Recovery to Grade 1 or better from prior therapy toxicities; at least 4 weeks since prior PD-1/PD-L1 inhibitors with resolved or stable adverse events
  • No contraindications to cold exposure and able to tolerate combined treatment
  • Negative pregnancy test for women of childbearing potential; agreement to use contraception during and 3 months after treatment
  • Able to understand and consent to study procedures and risks
  • For those planned for surgery, study procedures must not delay critical treatments
Not Eligible

You will not qualify if you...

  • Participation in another interventional trial or investigational treatment within 4 weeks before starting study treatment
  • Uncontrolled active infections including severe bacterial, viral, fungal infections, or active tuberculosis
  • HIV infection or chronic HBV/HCV with uncontrolled viral replication or unacceptable liver function
  • Known severe allergy to PD-1/PD-L1 inhibitors or their components
  • Active autoimmune disease or need for long-term moderate to high-dose immunosuppressive therapy
  • Prior severe or life-threatening immune-related adverse events from PD-1/PD-L1 therapy not resolved or high risk for re-exposure
  • Significant cardiovascular disease such as unstable angina, severe arrhythmia, heart failure class III-IV, low ejection fraction, recent heart attack, stroke, or thrombotic events within 6 months
  • Severe chronic respiratory diseases likely worsened by cold, like severe COPD or asthma
  • Clear contraindications to cold exposure including severe cold injury history, cold urticaria, cryoglobulinemia, active Raynaud's syndrome
  • Uncontrolled symptomatic central nervous system metastases
  • Severe psychiatric illness, cognitive impairment, substance abuse, or alcohol dependence affecting compliance
  • Pregnancy or breastfeeding
  • Uncontrolled diabetes, severe malnutrition, marked frailty, or other conditions impairing tolerance to cold or study procedures
  • Situations where study participation would significantly delay standard therapy, surgery, or critical treatments

AI-Screening

AI-Powered Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Run-in Period

Duration - 2 days

Participants undergo a cold acclimation phase with controlled exposure to mildly cold temperatures to prepare for the formal intervention.

2 consecutive days of cold exposure sessions before treatment starts

Treatment

Duration - Initial 7 days per cycle, repeated as tolerated during treatment (average 3 months)

Participants receive standard PD-1/PD-L1 inhibitor-based therapy combined with controlled cold exposure consisting of 12 hours per day in a temperature-controlled hospital room for 7 consecutive days. This intervention may be repeated in subsequent treatment cycles if tolerated.

Daily visits for 7 consecutive days per cycle during cold exposure combined with ongoing standard PD-1/PD-L1 therapy visits

Follow-up

Duration - Up to 36 months

Participants are monitored for safety, treatment response, and biological changes during and after treatment, including imaging assessments every 6-12 weeks and ongoing evaluations up to 36 months.

Imaging and clinical assessments every 6-12 weeks for up to 12 months; safety follow-up visits up to 30 days after last treatment

Trial Site Locations

Total: 1 location

1

West China Hospital of Sichuan University

Chengdu, Sichuan, China, 610041

Actively Recruiting

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Research Team

X

Xuelei Ma, M.D

S

Shen Li, M.D

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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Published Research Related To This Trial

Brown adipose tissue activation and cardiovascular risk following PD-1 antibody therapy in cancer patients: a retrospective cohort study.

Bingqian Lin, Duanyu Lin, Xiaodan Ou...

https://pubmed.ncbi.nlm.nih.gov/41316332