Clinical trial NCT04467723: Combination of Atezolizumab and Pirfenidone in Second-line and Beyond NSCLC
Official title: CAFs (Combination of Atezolizumab and Pirfenidone in Second-line and Beyond NSCLC): a Phase I/II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: NSCLC Stage IV
NSCLC, Recurrent
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: parkview cancer institute
First posted: 2020-07-13
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if adding pirfenidone to atezolizumab will increase anti tumor activity and reduce treatment resistance in stage 4 and recurrent non- small cell lung cancer participants.


Eligibility criteria: Inclusion Criteria:

* Participant or legal representative is able to provide written informed prior to performing any protocol-related procedures
* Is willing and able to comply with scheduled visits, treatment schedule, laboratory testing and other requirements of the study
* Men or women at least 18 years of age with histologically or cytologically confirmed non-small cell lung cancer
* Previous history of other than lung cancer is allowed if no active treatment for that cancer within 1 year
* Life expectancy of at least 6 months
* De novo stage IV or recurrent NSCLC without actionable mutation (e.g. EGFR/ ALK/ ROS-1) that was previously treated with either PD-1 / PD-L1 or the combination of PD1/PDL1 and cytotoxic chemotherapy, no more than 2 systemic regimens for metastatic disease with measurable disease \*. Maintenance therapy will be considered part of the 1 regimen
* At least 1 measurable lesion
* PDL1 TPS score less than 1% or unknown: first-line must be PD1/PDL1 inhibitor in combination with chemotherapy
* Early stage (I-III) NSCLC treated with adjuvant or neoadjuvant chemotherapy then PD1/PDL1 inhibitor treatment for recurrent disease
* Recurrent Unresectable stage III NSCLC treated with prior chemoradiation followed by maintenance PD1/PDL1 inhibitor with measurable disease
* Eastern Cooperative Group (ECOG) Performance Status 0 - 2
* Is able to swallow oral medications
* Adequate hematologic function
* Adequate organ function

Exclusion Criteria:

* The presence of any other concurrent severe and/or uncontrolled medical condition that would, in the investigator or treating physician's judgement, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol
* Has received investigational agents within 14 days or 5 half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
* Has a known hypersensitivity to atezolizumab or pirfenidone
* Has active medical or psychiatric illness that would interfere with the study treatment
* Has uncontrolled diabetes
* Has any of the following cardiac diagnoses:

Unstable angina Myocardial infarction within 6 months Uncontrolled congestive heart failure Left ventricular ejection fraction \< 35%

* Has a history of any Grade 3 or 4 toxicities to a prior checkpoint inhibitor treatment
* Is pregnant or breast feeding
* Uncontrolled HIV
* Clinically diagnosed with grade 2 or 3 radiation-induced lung injury within the last 3 months prior to registering for the study
* Has a history of idiopathic pneumonitis that required systemic agent including steroid
* Has drug-induced pneumonitis
* Has evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Smoker of more than 1 pack / day
* Has active peptic ulcer diagnosed within 4 weeks of enrollment
* Active infection requiring systemic treatment
* Current use of systemic antibacterial or antifungal agent
* Prior monoclonal antibody within 4 weeks before study Day 1 Exception: The use of denosumab
* Patient not recovered to ≤ Grade 1 from AEs due to agents administered more than 4 weeks earlier
* Concurrent use of other investigational agents
* Uncontrolled or symptomatic brain metastasis or leptomeningeal disease that requires use of steroids
* Use of strong CYP1A2 inhibitors
* Previous history of cancer with active treatment within less than 1 year of enrollment
* Active auto-immune diseases

Primary outcomes:
measure: Occurrence of Grade 3 toxicity
timeFrame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)
measure: Occurrence of Grade 4 toxicity
timeFrame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)
Secondary outcomes:
measure: Overall response rate (ORR) of participants
timeFrame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)
measure: Progression Free Survival (PFS)
timeFrame: From Cycle 1 day 1 (Each cycle is 21 days) for up to 2 years after end of treatment
measure: 1-year overall survival (OS) rate: Proportion of participants alive at 1 year from Cycle 1 day 1
timeFrame: Cycle 1 day 1 up to 1 year post-Cycle 1 day 1 (Each cycle is 21 days)
Other outcomes:
Locations:
city: Fairway
country: United States
facility: The University of Kansas Cancer Center (KUCC)
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, Westwood Campus
state: Kansas
Study officials:
affiliation: The University of Kansas
name: Chao Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: