臨床研究等提出・公開システム

A phase2 study to evaluate the efficacy and safety of weekly nab-paclitaxel in combination with carboplatin in patients with cancer of unknown primary (Efficacy and safety of weekly nab-paclitaxel plus CBDCA in patients with CUP)

Efficacy and safety of weekly nab-paclitaxel plus CBDCA in patients with CUP (Efficacy and safety of weekly nab-paclitaxel plus CBDCA in patients with CUP)

17

Median age 63(44-80), PS0:11cases, PS1: 6 cases Male 9 cases, and female 8 cases (histology) adenocarcinoma 9, cancer 2, malignant epitheloid tumor 1, poorly differentiated adenocarcinoma 3, squamous cell carcinoma 1, squamotransitional carcinoma 1.

All enrolled patients satisfied the inclusion criteria, and were treated with the trial treatment. Patients were enrolled at the scheduled pace until 2017. But the last patient was enrolled on January 24, 2018, and after that, no new patient was enrolled. Because of the spread of cancer gene panel tests, registration of new CUP patients cannot be expected, so this clinical trial is discontinued.

There was one TRD case. He died just after the first course of the trial treatment. The main reason of his death was suspected to be adrenal insufficiency caused by adrenal metastasis. On September 8,2014, the protocol was modified to exclude patients with adrenal insufficiency requiring treatment. grade1 grade2 grade3 grade4 fatigue 6(35.3) 0 0 0 anorexia 3(17.7) 1(5.9) 0 0 mucositis oral 1(5.9) 1(5.9) 0 0 nausea 5(29.4) 1(5.9) 0 0 vomiting 0 1(5.9) 0 0 constipation 10(58.8) 1(5.9) 0 0 diarrhea 2(11.8) 0 0 0 rash maculo-papular 1(5.9) 0 0 0 peripheral sensory neuropathy 6(35.3) 1(5.9) 1(5.9) 0 anemia 5(29.4) 8(47.1) 3(17.7) 0 neutrophil count decreased 1(5.9) 2(11.8) 6(35.3) 7(41.2) platelet count decreased 6(35.3) 7(41.2) 1(5.9) 0 AST increased 10(58.8) 0 0 0 ALT increased 2(11.8) 4(23.5) 0 0 Creatinine increased 3(17.7) 0 0 0 hyponatremia 5(29.4) 0 1(5.9) 0 hypernatremia 1(5.9) 0 0 0 hypokalemia 2(11.8) 0 0 0 hyperkalemia 2(11.8) 1(5.9) 0 0 hypocalcemia 1(5.9) 1(5.9) 0 0 hypercalcemia 1(5.9) 0 0 0

Response rate was 41,2%. 50% of PFS was 28.9weeks. 50% of OS cannot be calculated due to deficiency of events.

This study was discontinued prematurely and the number of enrolled patients was a few. So, it does not lead to a certain conclusion. Judging from enrolled 17 cases, the RR and 50% of PFS were 41.2% and 28.9 weeks, respectively.

Feb. 18, 2021

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs051180084

Yagi Toshinari

Osaka International Cancer Institute

3-1-69 Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 Japan

yagi-to@mc.pref.osaka.jp

Yagi Toshinari

Osaka International Cancer Institute

3-1-69 Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567 Japan

+81-6-6945-1181

yagi-to@mc.pref.osaka.jp

Complete

Nov. 05, 2013

Interventional

single arm study

open(masking not used)

historical control

single assignment

treatment purpose

1)Patients with histologically comfirmed metastatic malignant lesion, with no identifiable primary site by physical examination, imaging, and laboratory examination.
2)No indication for radical operation and radiotherapy.
3)Measurable disease according to RECIST(version1.1).
4)No prior chemotherapy for CUP.
5)ECOG scale: 0-1
6)Patient with enough feasibility for planned chemotherapy(hematological, liver, renal, cardiopulmonary function).
7)peripheral neuropathy <= Grade1
8)Patients who are expected to survive for more than 3 months.
9)Written informed consent.

1) Pregnancy or breast feeding.
2)Patients unable to take nab-paclitaxel and CBDCA because of significant cardiovascular abnormalities, renal dysfunctions, hepatic insufficiency, uncontrolled diabetes, uncontrolled hypertension, bleeding tendency, active interstitial pneumonia,etc.
3)Known HIV active hepatitis B, active hepatitis C, and/or other known severe infections, including but not limited tuberculosis.
4)Ascites, pleural effusion, pericardial effusion, which require regular drainage.
5)Any other active malignancy unless free of disease for at least five years.
6)Known active brain metastasis.
7)Known hypersensitivity to any of platinum drugs, paclitaxel, and albumin containing drugs.
8)Known hypoadrealism which requires treatment
9)Specific clinicopathologic subgroups which have effective management.
a)Woman with isolated axillary lymph node metastasis.
b)Patients with CUP presenting as metastatic cervical or isolated inguinal lymphadenopathy(squamous cell carcinoma).
c)Men with features of the extra gonadal germ cell cancer syndrome.
d)Men with features of prostate cancer(adenocarcinoma, elevated level of PSA, and osteoblastic bone metastasis).
e)Neuroendcrine tumors.

Both

cancer of unknown primary

Nab-paclitaxel is administered as a 30-minute infusion at a dose of 100mg/m2 on days 1,8,and 15 followed by carboplatin at an AUC of 6 mg.min/ml(per Calvert formula) given on day1, every 21 days. Responding patients and patients with stable disease have a six-cycle maximum.

CUP, nab-Paclitaxel,CBDCA

response rate

progression free survival, overall survival, adverse event

+81-6-6945-1181

Jan. 18, 2019

none