臨床研究等提出・公開システム

A phase II study to evaluate prophylactic treatment of dacomitinib-induced dermatologic adverse events in EGFR-mutated advanced non-small cell lung cancer (SPIRAL-Daco study)

A phase II study to evaluate prophylactic treatment of dacomitinib-induced dermatologic adverse events in EGFR-mutated advanced non-small cell lung cancer (SPIRAL-Daco study)

41

Forty-one patients aged 20 years or older with EGFR mutation-positive advanced/recurrent non-small-cell lung cancer were enrolled. All Forty-one enrolled cases were eligible for FAS and SAS analysis. There were no violations of eligibility criteria, exclusion criteria, concomitantly prohibited drugs, or concomitantly prohibited therapies, and all patients were eligible for PPS. There were 20 male (48.8%) and 21female (51.2%) patients. The histological types were adenocarcinoma in 40 patients (97.6%) and large cell neuroendocrine carcinoma in only 1 EGFR gene mutations consisted of the exon 19 deletion in 19 patients (46.3%) and the exon 21 L858R point mutation in 19 patients (46.3%) .

Case collection started in Nov 2019. The final enrollment was 41 subjects against the target number of 40 subjects (registration ended Apr 20, 2021).

Severe adverse events were as follows. diarrhea grade2, vomiting grade2, liver dysfunction grade3, pneumonitis grade2(2 patients), pneumonitis grade3(2 patients), musculoskeletal and connective disorders - other specified grade4, All events recovered except one case, which was occurred in one case of pneumonitis (grade3). The patient complicated with pneumonitis (grade3) passed away due to lung cancer before recovery of pneumonitis.

Primary endpoint Incidence of skin toxicities (>= grade2) during initial 8 weeks after dacomitinib administration. Skin toxicities (>= grade2) occurred in 18 patients (43.9%). Upper limit of 90% confidence interval was 56.7%, which was over 46% (pre-planned threshold). Therefore, primary endpoint was not met. Secondary endpoints Dose reduction proportion due to skin toxicities. Skin toxicities caused dose reduction of dacomitinib treatment in 8 patients (8/41, 19.5%). The number of one stage reduction was 7 patients, and that of two stage reduction wad one. Total reduction proportion was 19.5%. Progression free survival (PFS) Median PFS was 27.0 weeks (95% CI, 15.9-34.3 weeks) Safety The incidence of skin toxicity was 34 patients (82.9%) for paronychia, 32 patients (78.0%) for dry skin, and 31 (75.6%) for rash acneiform, high in that order. The most frequent subjective symptoms were diarrhea in 34 patients (82.9%) , oral mucositis in 25 patients (61.0%), fatigue in 23 patients (56.1%), and anorexia in 21 patients (51.2%), high in that order. Grade 3 or more adverse skin toxicity events was 7 patients(17.1%). rash acneiform in 3 patients (7.3%), paronychia in 2 patients (4.9%), erythema multiforme in 2 patients (4.9%), and skin infection in 1 patient (2.4%). Grade 3 or more adverse events was 17 patients (41.5%). The most common adverse event was anorexia in 6 patients (14.3%), followed by oral mucositis in 4 patients (9.8%).

This prospective trial aimed to evaluate the effect of prophylactic intervention for skin toxicities, due to dacomitinib treatment. We enrolled 41 patients. As for Primary endpoint,18 patients(43.9%) had skin toxicities(>= grade2) in initial 8 weeks. The Upper limit of 90%CI was over pre-planned threshold. Skin toxicities caused dose reduction of dacomitinib treatment in 8 patients(19.5%). Grade3 or more adverse events was 17 patients (41.5%). The most common adverse event was anorexia in 6 patients(14.6%).

Sept. 01, 2023

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs071190015

Takayama Koichi

University Hospital, Kyoto Prefectural University of Medicine

465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, JAPAN

takayama@koto.kpu-m.ac.jp

Iwasaku Masahiro

University Hospital, Kyoto Prefectural University of Medicine

465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, JAPAN

+81-75-251-5513

miwasaku@koto.kpu-m.ac.jp

Complete

May. 15, 2019

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1.Patients are >=20 years old (at the time of providing informed consent)
2. Patients with histolog ically or cytolog ically
confirmed non-small cell lung cancer
3. Patients with EGFR mutation positive
4. Patients at a stag e of IIIB/IIIC or IV who are inoperable or who experienced postoperative recurrence
5. No treatment history of dacomitinib
6. Patients with at least 1 measurable lesion
according to RECIST v1.1 criteria
7. Patients with performance status (ECOG) of 0-2
8. Patients for whom bone marrow, hepatic, and renal functions have all been confirmed as normal within 2 weeks prior to enrollment according to the following clinical test
White blood cell count>= 3.0x10^3/uL -12.0x10^3/uL
Neutrophil count >= 1.5x10^3/uL
Platelet count >= 100x10^3/uL
Hemoglobin >= 9.0 g/dl
AST <= 100 IU/L
ALT <= 100 IU/L
Total bilirubin <= 1.5xULN
creatinine <= 1.5xULN
SpO2 (Room air) >=90%
9. Patients whose following period after prior treatment passed in the planned starting point of administration (eligible from the same day after passed period)
Chemotherapy: passed >= 2 weeks after the final administration
EGFR-TKI: the next day after the last administration if there is no skin adverse event attributable to ore-treatment of EGFR-TKI or it is improved by <= Grade 1 of skin adverse event
Radiation therapy in the case of chest radical irradiation: passed >= 4 weeks after the day of final radiation
10. Patients providing the written informed consent

1. Patients with active double cancer (synchronous double cancer and metachronous double cancer within 5 years of disease-free interval. However, the lesions correspondent to carcinoma in situ and intramucosal carcinoma curable by topical treatment are excluded)
2. Patients without intention of preventing contraception or whose partner plans to pregnant during the study period
3. Patients who are pregnant, nursing or possibly pregnant
4. Patients who are different for the participation in the study by complication of mental disease or psychiatric symptom.
5. Patients with pulmonary disorders such as interstitial pneumonia, active radiation pneumonitis or drug-induced pneumonia
6. Patients with intestinal paralysis and ileus
7. Patients unable to swallow oral medications
8. Patients with infectious disorder need for intravenous injection of antibacterial drug and antimycotics
9. Patients with spinal cord compression, or unstable brain metastasis accompanying symptoms (however, the participation is possible if neurological function is clinically stable by radical cure treatment and more than 14 days passed after the secession of steroid therapy)
10. Patients with uncontrollable diabetes mellitus(eligible when control is considered good even if insulin is used continuously)
11. Patients with history of hypersensitivity to drugs (skin moisture, sunscreen, topical steroid for external use) and tetracycline agent used in this study
12. Patients who have complications to be clinical problem
(Such as sever or uncontrollable systemic disease)
uncontrollable hypertension
complication of unstable angina pectoris (angina pectoris onset within latest 3 weeks or with progression of spasm) or anamnesis of myocardial infarction within 6 months
severe cardiac arrhythmia to need medical treatment
sustained watery diarrhoea
active bleeding
13. Any other patients who are regarded as unsuitable for this study by the investigators.

Both

non-small cell lung cancer

Dacomitinib 45mg/day, OD is orally administered until PD or the meeting of discontinuation criteria.
Treatment for skin disorder is carried out from the first day of dacomitinib administration to 8 weeks.
[RP01] Oral minocycline (100mg/day) is administered; Once a day or twice a day after breakfast and dinner.
[RP02] Heparinoid is applied twice a day (morning and evening)
[RP03] Hydrocortisone butyrate formulation is applied twice a day (morning and evening)
[RP04] Difluprednate is applied twice a day (morning and evening)
[RP05] Sun screen is applied before going out (SPF25, PFA >=4 and<8, UVA/UVB protection)

non-small cell lung cancer

Incidence of >= grade 2 skin toxicities during 8 weeks after dacomitinib administration

Dose reduction rate of dacomitinib, safety, progression free survival rate (PFS)

+81-92-643-7171

June. 05, 2019

none