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Phase I study of Amrubicin plus CISplatin and concurrent accelerated hyperfractionated thoracic radioTherapy for limited-disease small cell lung cancer (ACIST study)

Phase I study of Amrubicin plus CISplatin and concurrent accelerated hyperfractionated thoracic radioTherapy for limited-disease small cell lung cancer (ACIST study)

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The median age was 67 years (range: 58-75). There were 7 patients with performance status (PS) 0 and 2 with PS 1. The cohort included 6 men and 3 women, all of whom were smokers. Disease stage was II in 3 cases and III in 4 cases.

If DLTs were not observed in the initial three patients, we planned to add six patients and evaluate the RD and MTD. If DLTs were confirmed in one of the first three patients enrolled, we planned to add three additional patients. If DLTs were confirmed in none of the additional three patients, we will add six additional patients and evaluate the RD and MTD. If DLTs were confirmed in more than one of the additional three patients, 25 mg/m2 will be established as the MTD. If DLTs were confirmed in more than two of the first three patients, we planned to add three patients to receive a reduced dose of 20 mg/m2 and evaluate the RD and MTD.

One patient required emergency hospitalization due to Grade 4 neutropenia and Grade 3 febrile neutropenia without G-CSF prophylaxis. After consultation with the attending physician, study administration office, and principal investigator, the event was assessed as having a causal relationship, being serious, and an expected SAE. It was referred to the efficacy and safety evaluation committee, and it was determined that reporting to the CRB was not necessary.

The primary endpoint of this study was to determine the recommended dose (RD) of amrubicin in combination with cisplatin chemotherapy and concurrent accelerated hyperfractionated thoracic radiotherapy for limited-stage small cell lung cancer. The RD of amrubicin was 25 mg/m2. The secondary endpoints were as follows; Maximum tolerated dose (MTD): 25 mg/m2, Dose-limiting toxicity (DLT): Febrile neutropenia Grade 3, thrombocytopenia Grade 4, Overall response rate: 100%, median progression-free survival: Not reached, and median overall survival: Not reached.

The recommended dose of amrubicin in combination with cisplatin chemotherapy and concurrent accelerated hyperfractionated thoracic radiotherapy for limited-stage small cell lung cancer was 25 mg/m2, with tolerable toxicity and favorable overall survival outcomes. Amrubicin may represent a promising therapeutic option for limited-stage small cell lung cancer.

Oct. 31, 2025

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCT1071200033

Taniguchi Hirokazu

Nagasaki University Hospital

1-7-1, Sakamoto, Nagasaki, Nagasaki

hirokazu_pc@nagasaki-u.ac.jp

Akagi Kazumasa

Nagasaki University Graduate School of Biomedical Sciences

1-7-1 Sakamoto, Nagasaki, Nagasaki

+81-95-819-7273

kaz.keepthefaith@gmail.com

Complete

Sept. 30, 2020

Interventional

single arm study

open(masking not used)

dose comparison control

single assignment

treatment purpose

1) Histologically or cytologically confirmed small cell lung cancer. Combined small cell lung cancer is acceptable.
2) Limited disease
3) Age between 20-75 when registered
4) Performance status (ECOG) 0 or 1 when registered
5) Regardless of measurable lesions
6) No prior chemotherapy
7) No active multiple cancer
8) The latest clinical laboratory test within 14 days prior to registration meets the following;
1. Neutrophil count >=1500 / mcL
2. Platelet count >=10X104 / mcL
3.Total-Bilirubin =<1.5 mg/ dL
4. Aspartate aminotransferase =<100 U/ L
5. Alanine aminotransferase =<100 U/ L
6. Serum creatine =<1.2 mg/dL
7. SpO2 >=92 %
8. Radiologists expect sufficient respiratory function to be preserved after the chemoradiotherapy. Calculating the actual value of V20(volume of normal lung irradiated over 20 Gy compared to all lung volume) or proportion of irradiation field for one-lung is not necessary before registration and the estimation by chest X ray or computed tomography is acceptable. Evaluation criteria whether desirable respiratory function is preserved after radiotherapy is V20 =<35 .
9) Written informed consent

1) Lobectomy is acceptable
2) Symptoms by pericardial effusion
3) Urgent radiation therapy is necessary for superior vena cava syndrome.
4) Persistent angina, myocardial infarction within three months, persistent heart failure
5) Persistent diabetes
6) Persistent Hypertension
7) Active systemic infection calling for treatment
8) Pregnant, possibly pregnant, postpartum within 28 days, breastfeeding, men considering childbirth.
9) Body temperature over 38.0 degrees Celcius
10) Mental disorder or symptoms interfere with daily life and judged to be inappropriate to enroll.
11) Continuous intravenous or oral administration of steroids or immunosuppressants
12) HBs antigen positive or HCV antibody positive.
13) HIV antibody positive (not necessarily examined)
14) Computed tomography shows interstitial pneumonia, pulmonary fibrosis or emphysema.
15) Other in appropriate complications

Both

Limited-disease small cell lung cancer

4 courses of chemotherapy below are administered every 4 weeks.
course 1
AMR day1-3 25-20 mg/m2/day
CDDP day1 60 mg/m2/day
course 2-4
AMR day1-3 35 mg/m2/day
CDDP day1 60 mg/m2/day
Radiotherapy(1.5 Gy, twice daily, 5 days a week, total 45 Gy) is administered from day2 of course 1.

recommended dose

maximum tolerated dose, dose limiting toxicity, response rate, overall survival, progression free survival, adverse effects

+81-95-819-7229

Aug. 31, 2020

none