UMIN-CTR Clinical Trial

Basic information
Public title	Phase II Study of Carboplatin+nab-Paclitaxel for Non-small Cell Lung Cancer with Interstitial Pneumonitis
Acronym	Phase II Study of Carboplatin+nab-Paclitaxel for Non-small Cell Lung Cancer with Interstitial Pneumonitis
Scientific Title	Phase II Study of Carboplatin+nab-Paclitaxel for Non-small Cell Lung Cancer with Interstitial Pneumonitis
Scientific Title:Acronym	Phase II Study of Carboplatin+nab-Paclitaxel for Non-small Cell Lung Cancer with Interstitial Pneumonitis
Region	Japan

Condition
Condition	Advanced Non-small Cell Lung Cancer with Interstitial Pnumonitis
Classification by specialty	Pneumology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To assess the safety and efficacy of carboplatin plus nab-paclitaxel in patients with advanced non-small-cell lung cancer with interstitial pneumonitis.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Treatment completion rate (>=4cycles)
Key secondary outcomes	Overrall response rate(ORR), Disease control rate(DCR), Progression free survival(PFS), Overall survival (OS), Safety (frequency of of acute exacerbation of interstitial pneumonitis, frequency of the other adverse effects)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Four to six cycles of Carboplatin day1(AUC5) plus Nab-Paclitaxel day1,8,15 (100mg/m2) every 4 weeks .
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	1)Histologically or cytologically confirmed non-small cell lung cancer (if mixed type, judged by major histology) 2)Clinical stageIIIA, IIIB not amenable to curative treatment or stage IV, or post operative reccurence (TNM classification, 7th edition) 3) Eligible with or without EGFR mutation , Eligible with or without ALK translocation 4) Interstitial pneumonitis confirmed by high resolution chest CT (less than 2.5mm slice) eligible pirfenidone or inhalation of NAC without the activity of interstitial pnumonitis eligible secondary interstitial pnumonitis except IIP fill at least 2 of the following radiological findings and eligible judged by central review; honeycoming, traction ectasia, ground-grass opacity, interlobular septal thickening 5) Patients aged 20-79 6) ECOG PS 0-1 7) Patients are excepted to live at least 12 weeks 8) Eligible with or without measurable lesions 9) No prior chemotherapy (eligible; In case of postoperative recurrence, 8 weeks or more than 8 weeks after operation. If performed adjuvant chemotherapy, equal or more than 6 months after the day of the final adjuvant chemotherapy) 10) Adequate organ function, evaluated within 14 days before enrollment WBC >=3,000/mm3 Neu >=1,500/mm3 Plt >=100,000/mm3 Hb>=9.0g/dl AST<=2.5XULN, /ALT<=2.5XULN T.Bil<=1.5mg/dl sCr<=1.5mg/dl PaO2>= 70torr 11) less than Grade 2 peripheral neuropathy 12) Written informed consent from the patients 13) No prior radiation therapy for primary cancer (eligible palliative radiation therapy except primary lesion which has done more than 2 weeks before.
Key exclusion criteria	1) Active double cancer 2) Being suspected acute or sub-acute exacerbation of interstitial pneumonitis. Being experienced acute exacerbation of idiopathic interstitial pneumonia. 3) Receiving steroids or immunosuppressants within 3 month for interstitial pneumonia 4) Patiens has pleural effusion, pericardial effusion and ascites to need dranage 5) Serious complications as follows; History of uncontrollable angina pectoris, acute myocardial infarction or heart faliure, etc within 6 months History of cerebral infarction within 6 months Uncontrollable diabetes mellitus, hypertension and diarrhea Active infectious disease or suspected active infectious disease Other Serious complications (ileus, bleeding tendency , SVC syn. Varicella etc) 6) symptomatic brain metastasis 7) Pregnancy, breast feeding and suspected or wish of pregnancy. Men and women who declined contraception 8) Patients who have serious drug hypersensitivity reaction 9) Patients who have received a radiation therapy in chest 10) Having a schedule of operations 11) Patients whose participation in the trial is judged to be inappropriate because of psychiatric disease or psychiatric symptoms 12) Positive HBs antigen 13) Patients whose participation in the trial is judged to be inappropriate by the investigators
Target sample size	30

Research contact person
Name of lead principal investigator	1st name Middle name Last name Miyazaki Yasunari
Organization	Tokyo Medical and Dental university
Division name	Department of Integrated Pulmonology
Zip code
Address	1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
TEL	03-5803-5954
Email	ninase@tmd.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Hiroyuki Sakashita
Organization	Tokyo Medical and Dental university
Division name	Department of Integrated Pulmonology (Clinical Oncology)
Zip code
Address	1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
TEL	03-5803-5954
Homepage URL
Email	hsakashita.pulm@tmd.ac.jp

Sponsor
Institute	Yushima Lung Cancer Oncology Group(YLOG)
Institute
Department

Funding Source
Organization	Department of Integrated Pulmonology, Tokyo Medical and Dental university
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2014 Year 11 Month 12 Day

Related information
URL releasing protocol	https://onlinelibrary.wiley.com/doi/10.1111/1759-7714.14376
Publication of results	Published

Result
URL related to results and publications	https://onlinelibrary.wiley.com/doi/10.1111/1759-7714.14376
Number of participants that the trial has enrolled	25
Results	The 4-week modified regimen of carboplatin and nab-paclitaxel showed tolerable toxicity with favorable efficacy in NSCLC patients with ILD. This regimen may be an effective treatment option for patients in real clinical settings.
Results date posted	2022 Year 05 Month 03 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	The median age was 71 years, and 23 patients were male. Fifteen patients had PS 0 (60%), and the rest were PS 1 (40%). Adenocarcinoma, Sq, and large cell carcinoma were observed in nine (36%), 11 (44%), and one (4%) patient, respectively, and the others were categorized as not otherwise specified. Nine patients (36%) were EGFR mutation negative, and the rest of patients were unknown. Seven patients (28%) were ALK rearrangement negative, and the rest of patients were unknown. Two patients (16%) were never smokers. Among the imaging findings for ILD on HRCT, honeycombing, traction bronchiectasis, interlobular septal thickening, and ground grass opacity were observed in 12 (48%), 23 (92%), 21 (84%), and 21 (84%) patients, respectively. Two patients were diagnosed with RA, manifesting as RA-related ILD at enrollment. Two other patients showed anticyclic citrullinated peptide (CCP) antibody positivity without symptoms of RA at the time of enrollment, but one of them was later diagnosed with RA and RA lung. The other patients were considered idiopathic. The positive incidence rate and median serum level of KL-6 were 84% and 747 U/ml, respectively.
Participant flow	Nineteen patients (76%) received four or more cycles of the protocol treatment.
Adverse events	The most common hematological grade 3 or 4 adverse event was neutropenia (48%), while febrile neutropenia was not observed. The most common nonhematological adverse events were fatigue (76%), followed by appetite loss (60%). Peripheral neuropathy was observed in 10 patients (40%) without grade 3 or 4 neuropathy. Three patients experienced 2 or more than grade 2 pneumonitis, and one patient met the acute exacerbation criteria.
Outcome measures	Of the 25 patients enrolled in our study, one patient (4%) achieved CR, 10 patients (40%) showed PR, and 11 patients (44%) had SD. Only one patient showed progressive disease (PD), and two patients had a disease status that could not be evaluated. Thus, the ORR and DCR were 44% and 88% respectively. The unconfirmed ORR response rate was 64%. The median PFS and OS were 5.8 months and 15.8 months, respectively.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 07 Month 20 Day
Date of IRB	2014 Year 09 Month 26 Day
Anticipated trial start date	2014 Year 11 Month 12 Day
Last follow-up date	2021 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2014 Year 11 Month 11 Day
Last modified on	2022 Year 05 Month 03 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000018059