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A Phase II Study of Carboplatin and Etoposide Plus Nintedanib for Unresectable Limited/Extensive Disease Small Cell Lung Cancer with Idiopathic Pulmonary Fibrosis (TORG1835 / NEXT-SHIP)

A phase II Study of CBDCA + ETP + Nintedanib for SCLC with IPF

33

The median age of all 33 enrolled patients was 73 (63-80) years, 9 had PS 0, 22 had PS 1, 2 had PS 2, 29 were male and 4 were female. 7 patients had LD and 26 had ED. The median %FVC and %DLco at enrollment were 85.2% and 71.6%, respectively. All patients had a history of smoking.

Twenty-one facilities participated, and registration proceeded at a faster pace than planned, with accumulation completed in 2 years and 3 months instead of the planned 3 years. The number of registrations per institution were; 4 each from Yokohama City Municipal Hospital and Kurume University Hospital, 3 each from 4 institutions, 2 each from 6 institutions, and 1 from 1 institution. 8 institutions did not register any cases. A stopping rule was established to advise the Efficacy and Safety Evaluation Committee whether or not to continue the study if there were three or more cases of Grade 3 pneumonitis at the time of enrollment of 10 patients. However, after the 19th case, 4 cases (14.8%) of pneumonia occurred at the time of enrollment of 27 cases, and were reported to the Efficacy and Safety Evaluation Committee and the CRB. Although the frequency was within the expected range, the occurrence of pneumonitis Grade 5 led to a protocol revision to perform a central determination of baseline CT images for all patients for accurate evaluation of the background lung and risk factor analysis of acute exacerbations of IPF. The majority of patients withdrew due to worsening or relapse of the SCLC (28 patients), and 2 patients withdrew consent. Twenty-six patients (78.8%) were switched to maintenance therapy, and the median duration of nintedanib, including posttreatment, was 162 days. administration

One treatment-related death: Death due to irreversible progression of respiratory failure caused by acute exacerbation of interstitial pneumonia, which was judged to be causally related. One case of progression of primary disease: After one course of treatment, the patient died due to progression of primary disease after PD due to increased left pleural effusion and aggravation of liver metastasis, despite the appearance of Grade 2 pulmonary inflammation. The efficacy and safety evaluation committee determined that there was no causal relationship. The most common adverse event>=grade 3 was neutropenia (81.8%), followed by leukopenia (39.4%) and thrombocytopenia (30.3%).

The primary endpoint of the study, the incidence of acute exacerbation of IPF at 28 days after last administration of cytotoxic chemotherapy, was observed in one patient, at a rate of 3.0% (90% CI: 0.2-13.6). The threshold (upper limit of 90% CI) of 20% specified in the protocol was not exceeded, and the primary endpoint was met. The secondary endpoint of the rate of IPF acute exacerbations during the follow-up period was 12.1% (95% CI: 3.4-28.2). The median IPF acute exacerbation-free survival was 12.4 months (95% CI: 7.7-20.4). The overall response rate was 69.7% (95% CI 51.3-84.4). Median progression-free survival and overall survival were 4.2 (95% CI 4.2-5.5) and 13.4 (95% CI 8.1-21.6) months, respectively.

Conclusion: The study met its primary endpoint regarding the incidence of acute exacerbations of IPF and showed promising results for efficacy.

Feb. 19, 2024

Feb. 19, 2024

https://doi.org/10.1513/AnnalsATS.202311-941OC

No

We have no plans to share IPD data.

https://jrct.mhlw.go.jp/latest-detail/jRCTs031190119

IKEDA Satoshi

Kanagawa Cardiovascular and Respiratory Center

Tomioka-higashi 6-16-1, Kanazawa-ku, Yokohama, Kanagawa

isatoshi0112@gmail.com

IKEDA Satoshi

Kanagawa Cardiovascular and Respiratory Center

Tomioka-higashi 6-16-1, Kanazawa-ku, Yokohama, Kanagawa

+81-45-701-9581

isatoshi0112@gmail.com

Complete

Oct. 18, 2019

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Histologically or cytologically proven small cell lung cancer
2. Unresectable limited disease or extensive disease
3. No previous chemotherapy for small cell lung cancer
4. HRCT reveal (1) Definite honeycomb lung destruction with basal and peripheral predominance : or (2) Presence of reticular abnormality and traction bronchiectasis consistent with fibrosis with basal and peripheral predominance
5. % FVC >= 50 , % DLCO >= 30 %
6. Age >= 20 years
7. ECOG Performance Status 0-2
8. With measurable lesions according to RECIST Version1.1
9. Vital organ functions are preserved
10.Received sufficient explanations about the name and severity of the illness
11. Written informed consent

1. Ground glass opacity pattern less extensive than reticular opacity pattern
2. Other interstitial lung disease of known etiology (including infection, pneumoconiosis, drug-induced pneumonitis, sarcoidosis, and collagen vascular disease)
3. History of acute exacerbation of IPF
4. Synchronous or metachronous active double malignancies
5. Symptomatic brain metastasis or spinal cord metastases
6. Treatment history with pirfenidone, immunosuppressants, and N-acetylcysteine within 56 days before registration
7. Treatment history with nintedanib, cytotoxic chemotherapy, and immune checkpoint inhibitors
8. High hemorrhage risk
9. Serious complications
10. Local or systemic active infection requiring treatment
11. Pregnant, possibly pregnant, breastfeeding
12. History of serious drug allergies
13. Systemic treatment with steroids at a daily dose >10 mg of prednisolone equivalent
14. Other conditions not suitable for the study

Both

Unresectable limited or extensive disease small cell lung cancer with idiopathic pulmonary fibrosis

The patients receive carboplatin(area under the curve 5 mg/mL, intravenously, day 1), etoposide (<75 years old:100mg/m2:>=75years old:80mg/m2;intravenously,days 1-3), and nintedanib (150mg twice a day, orally). The patients receive combination chemotherapy every3 weeks for 4 cycles until disease progression or unacceptable toxicity occurs. After completion or discontinuation of carboplatin plus etoposide, the patients continue nintedanib until the discontinuation criteria are satisfied.

the incidence of acute exacerbation of IPF at 28 days after last administration of cytotoxic anti-cancer agents (carboplatin and etoposide)

Time to first acute exacerbation of IPF, ORR, PFS, OS, and toxicities

+81-25-368-9343

Aug. 26, 2019

none