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Breathomics as Predictive Biomarker for Checkpoint Inhibitor Response

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ClinicalTrials.gov Identifier: NCT04146064
Recruitment Status : Recruiting
First Posted : October 31, 2019
Last Update Posted : March 11, 2020
Sponsor:
Collaborator:
University of Amsterdam
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:

Immunotherapy with agents stimulating the immune system to act against cancer are now a new standard of care in various cancers as lung cancer and melanoma, but also bladder cancer, kidney cancer and head & neck cancer. However, even though a subset of patients derives long-term benefit from these agents, depending of cancer type still at least half of patients do not respond to these new drugs. Our understanding of possible factors predicting whether a patient might actually benefit from immunotherapy is poor. Volatile organic compounds (VOCs) are gases exhaled with a person's breath, which are released into the lung from blood and bacteria and therefore can give information about infections as well as inflammation and possibly cancer cells in a person's body. Breath analysis of these VOCs with special devices called electronic noses (eNose) generate a specific electric signals patterns called breathprints. There is early evidence that specific breathprints can actually help to select patients who will be likely to benefit from immunotherapy.

This study is being undertaken in an effort to evaluate breathprint analysis as a potential predicting factor for benefit from immunotherapy, so that treatment selection can further be improved.

This study is designed to help us identify the role of breathprint analysis to better select patients for immunotherapy.


Condition or disease Intervention/treatment
NSCLC Melanoma Kidney Cancer Urothelial Carcinoma Head and Neck Cancer Other: Breathprint analysis and patient-reported outcomes

Detailed Description:

Immune checkpoint blockade with anti-PD-1 and anti-PD-L1 antibodies has become a new standard of care in several cancer types as NSCLC and melanoma. However, in biomarker-unselected patient populations, overall response rate (ORR) depending on type of cancer and whether single or combination treatment is chosen remains still only 20%-60%. Though overall well tolerated approximately 5-10% of patients treated with PD1/PD-L1 targeting agents will experience grade 3 or 4 toxicities, including potentially life-threatening auto-immune toxicities such as colitis, hepatitis, and pneumonitis. Therefore, due to high costs of treatment and its possible complications, improved selection of patients is a crucial goal and an easily available non-invasive, point-of-care test for better patient selection is very much needed.

A promising approach in this regard is the analysis of volatile organic compounds (VOCs) in breath. Breath analysis for the detection of VOCs is increasingly investigated for its utility in diagnosis and management of cancer. Electronic noses (eNoses) are promising as cheap and clinically-practical devices that are designed to detect patterns of VOCs. Recently published prospective observational data showed very promising discriminant function for breathprint analysis for non-response to immunotherapy in NSCLC patients.

The principle goal of this study is to validate a prior study that found that breathomics-based classifiers predicted 12-week early progression vs non-progression in advanced NSCLC patients treated with nivolumab or pembrolizumab. Secondarily, we will expand assessment of breathomic-based classifiers to include other cohorts of advanced tumors treated with ICI, and also consider using response instead of non-progression as an endpoint. Exploratory goals include refinement of the breathomics classifier using alternative machine-learning techniques, and correlate with other biomarkers of immunotherapy outcomes.

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Study Type : Observational
Estimated Enrollment : 425 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Breathomics as a Non-invasive, Inexpensive, Point-of-care Predictive Test for Immune Checkpoint Inhibitor Efficacy
Actual Study Start Date : February 24, 2020
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024


Group/Cohort Intervention/treatment
Validation cohort: NSCLC

Patients with advanced/metastatic NSCLC planned for IO-treatment in one of the following categories

  • Pembrolizumab monotherapy first-line
  • Pembrolizumab or nivolumab monotherapy in second or later line
Other: Breathprint analysis and patient-reported outcomes

Breathprint analysis: Patients will be providing breathprint samples into the eNose device at baseline and every 12 weeks thereafter as long as on immunotherapy treatment.

Questionnaires will be completed at the same timepoints.


Cohort 1: NSCLC
Patients with advanced/metastatic NSCLC planned for Pembrolizumab-chemotherapy combination therapy first-line
Other: Breathprint analysis and patient-reported outcomes

Breathprint analysis: Patients will be providing breathprint samples into the eNose device at baseline and every 12 weeks thereafter as long as on immunotherapy treatment.

Questionnaires will be completed at the same timepoints.


Cohort 2: Melanoma

Patients with advanced/metastatic melanoma planned for IO-treatment in one of the following categories

  • Nivolumab/ipilimumab combination treatment 1L
  • Pembrolizumab or nivolumab monotherapy treatment 1L
  • Ipilimumab monotherapy 2L
Other: Breathprint analysis and patient-reported outcomes

Breathprint analysis: Patients will be providing breathprint samples into the eNose device at baseline and every 12 weeks thereafter as long as on immunotherapy treatment.

Questionnaires will be completed at the same timepoints.


Cohort 3: Mixed solid tumor cohort
Patients with advanced/metastatic solid tumors such as Head&Neck tumors, kidney cancer and urothelial cancer planned for IO-treatment
Other: Breathprint analysis and patient-reported outcomes

Breathprint analysis: Patients will be providing breathprint samples into the eNose device at baseline and every 12 weeks thereafter as long as on immunotherapy treatment.

Questionnaires will be completed at the same timepoints.


Cohort 4: NSCLC
Patients with advanced/metastatic NSCLC planned for treatment with Chemotherapy-only (either platinum-based combination treatment or docetaxel monotherapy)
Other: Breathprint analysis and patient-reported outcomes

Breathprint analysis: Patients will be providing breathprint samples into the eNose device at baseline and every 12 weeks thereafter as long as on immunotherapy treatment.

Questionnaires will be completed at the same timepoints.





Primary Outcome Measures :
  1. 12 week Progression Rate in validation cohort [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Overall Survival (OS) in validation cohort [ Time Frame: 5 years ]
  2. Overall Response Rate (ORR) in validation cohort [ Time Frame: 5 years ]

Other Outcome Measures:
  1. Progression-free survival (PFS) in validation cohort [ Time Frame: 5 years ]
  2. 6 months clinical benefit rate (CR, PR or SD at 6 months after treatment start) in validation cohort [ Time Frame: 6 months ]
  3. 12 week Progression Rate in exploratory cohorts [ Time Frame: 12 weeks ]
  4. OS in exploratory cohorts [ Time Frame: 5 years ]
  5. Overall Response Rate (ORR) in exploratory cohorts [ Time Frame: 5 years ]
  6. PFS in exploratory cohorts [ Time Frame: 5 years ]
  7. 6 months clinical benefit rate in exploratory cohorts [ Time Frame: 6 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects included in this study are patients over the age of 18 years with a histologically-confirmed diagnosis of non-small cell lung cancer, melanoma or other solid tumor for which ICI-treatment is a standard of care. Patients must have advanced/metastatic disease and planning to receive ICI treatment (categories defined above) or chemotherapy treatment (cohort 4) at the Princess Margaret Cancer Centre/University Health Network. Study subjects will be consented specifically for that study.
Criteria

INCLUSION CRITERIA

  • Patients 18 years of age or older
  • Histologically confirmed advanced/metastatic non-small cell lung cancer, melanoma or solid tumor such as urothelial, kidney or head and neck cancer and planned treatment with

    • NSCLC validation cohort: Pembrolizumab or Nivolumab
    • NSCLC Cohort 1: Pembrolizumab-chemotherapy combination therapy 1L
    • Melanoma Cohort 2: Nivolumab/ipilimumab combination treatment 1L, Pembrolizumab or nivolumab monotherapy treatment 1L , Ipilimumab
    • Solid tumors Cohort 3: Any ICI-treatment, any line
    • NSCLC Cohort 4: Chemotherapy-only (either platinum-based combination treatment or docetaxel monotherapy)
  • At least one measurable lesion as defined by RECIST 1.1. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
  • Able to provide informed consent.

EXCLUSION CRITERIA

  • Patients who are unable to perform the breathing manoeuvres needed for eNose-analysis of exhaled air.
  • Patients who are unable to independently consent to participation in the trial.
  • Patients with severe, acute, or chronic medical conditions (including uncontrolled diabetes mellitus) or psychiatric conditions or laboratory abnormalities that in the opinion of the Investigator or their physician may cause undue harm or inconvenience to the patient, or that may interfere with the interpretation of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04146064


Contacts
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Contact: Sabine Schmid, MD 416-946-2000 ext 5288 sabine.schmid@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Sabine Schmid, MD       sabine.schmid@uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
University of Amsterdam
Investigators
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Principal Investigator: Geoffrey Liu, MD MSc UHN
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04146064    
Other Study ID Numbers: IO-Breathomics
19-5936 ( Other Identifier: CAPCR-University Health Network )
First Posted: October 31, 2019    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Health Network, Toronto:
breathprint analysis
immunotherapy
predictive biomarker
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Kidney Neoplasms
Carcinoma, Transitional Cell
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial