UMIN-CTR Clinical Trial

Public title

Phase I study of cisplatin ･ pemetrexed in combination with salazosulfapyridine targeting cancer stem cells in advanced non-squamous non-small cell lung cancer

Acronym

Phase I study of cisplatin ･ pemetrexed in combination with salazosulfapyridine targeting cancer stem cells in advanced non-squamous non-small cell lung cancer

Scientific Title

Phase I study of cisplatin ･ pemetrexed in combination with salazosulfapyridine targeting cancer stem cells in advanced non-squamous non-small cell lung cancer

Scientific Title:Acronym

Phase I study of cisplatin ･ pemetrexed in combination with salazosulfapyridine targeting cancer stem cells in advanced non-squamous non-small cell lung cancer

Region

Japan

Condition

Advanced non-squamous non-small cell lung cancer
(Stage IIIB/IV or postoperative recurrent)

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To evaluate the safety of combination therapy with cisplatin, pemetrexed, and salazosulfapyridine and determine the recommended dose (RD) of salazosulfapyridine in patients with advanced non-squamous non-small cell lung cancer

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Percentage of patients with dose-limiting toxicity (DLT)

Key secondary outcomes

Percentage of patients with at least 1 adverse event
Percentage of responders
Progression-free survival (PFS)
Pharmacokinetics

Study type

Interventional

Basic design

expanded access

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Dose of salazosulfapyridine of 1.5-7.5g per day (t.i.d), one (or two, or three, or four, or five) 500mg tablet each time. Until PD (include criteria for discontinuing) or 365 days from start of administration.

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

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Clinical stage III or IV or postoperative recurrent non-squamous non-small cell lung cancer that has not been treated with chemotherapy a) and cannot be treated with curative radiotherapy.
a) Neither EGFR tyrosine kinase inhibitors for EGFR mutation-positive patients nor ALK tyrosine kinase inhibitors in ALK fusion gene-positive patients are included in prior treatments.
b) In postoperative recurrent disease, at least 24 weeks have passed from the last dose of postoperative adjuvant chemotherapy, if applicable, and the postoperative adjuvant chemotherapy must not contain cisplatin or pemetrexed.
2. Aged 20 years or older at the time of informed consent.
3. Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
4. All of the following criteria are met based on the latest data obtained within 14 days before enrollment:
1) Neutrophil count >= 1,500/mm^3
2) Hemoglobin >= 9.0 g/dL
3) Platelet count >= 10*104/mm^3
4) Total bilirubin <= 1.5 mg/dL
5) AST (GOT) <= 100
6) ALT (GPT) <= 100
7) SpO2 >= 92% in indoor air. Patients with SpO2 < 92% are eligible if PaO2 is 60 torr or more.
8) Creatinine clearance >= 60 mL/min
Patients with estimated creatinine clearance < 60 mL/min are eligible if creatinine clearance is actually determined to be 60 mL/min or more using a 24-hour specimen of urine.
5. No symptomatic brain metastasis or spinal metastasis requiring irradiation or surgical procedure.
6. No Grade 3 or higher superior vena cava syndrome, pericardial effusion, pleural effusion, or ascites Patients with a history of pleural effusion are eligible if there is no evidence of Grade 3 pleural effusion at 2 weeks after discontinuation of drainage following intrapleural infusion of antimicrobials or OK432.
7. No palliative radiotherapy for metastatic lesion(s) within 14 days before enrollment.
8. Able to swallow oral medications.
9. Have given written consent to participate in the study after receiving detailed explanation of the study.

Key exclusion criteria

1. Patients with an infection requiring systemic treatment.
2. Patients who cannot be in the hospital throughout the first DLT evaluation period of the cisplatin-pemetrexed-salazosulfapyridine combination therapy.
3. Patients with clinically significant psychiatric disease or symptom that would interfere with participation in this study.
4. Patients treated with an immune suppressor (oral or intravenous).
5. Patients with unstable angina (new-onset angina or exacerbation of angina within the last 3 weeks) or poorly controlled hypertension or diabetes mellitus.
6. Positive for hepatitis B surface (HBs) antigen or positive hepatitis C virus (HCV) antibody.
7. Evidence of interstitial pneumonia or pulmonary fibrosis in chest CT scan
8. History of hypersensitivity to sulfa drugs or salicylic acid preparations
9. Patients with ulcerative colitis or treatment with salazosulfapyridine or 5-ASA derivatives.
10. Pregnant or lactating females (including the females who canceled the breastfeeding before participating to the study and have possibility to re-start the nursing). Females of child-bearing potential with the positive result of the urine pregnancy test that was carried out within 14 days before registration.
11. Nonsterilized males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol (section 6.4., 5) ).
12. Patients who have participated to other clinical studies within 12 weeks before the consent obtaining. However, the drug information that has been administered in the clinical trial has become clear, so that the investigator (sub-investigator) except if that there is no impact on the participation of the clinical trial.
13. Any other condition, which in the opinion of the investigator or sub-investigator would preclude participation in the study.

Target sample size

30

Name of lead principal investigator

1st name
Middle name
Last name	Isamu Okamoto

Organization

Kyushu University Hospital

Division name

Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University and Center for Clinical and Translational Research of Kyushu University Hospital

Zip code

Address

3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

TEL

092-642-5378

Email

okamotoi@kokyu.med.kyushu-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Isamu Okamoto

Organization

Kyushu University Hospital

Division name

Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University

Zip code

Address

3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

TEL

092-642-5378

Homepage URL

Email

okamotoi@kokyu.med.kyushu-u.ac.jp

Institute

Kyushu University Hospital

Institute

Department

Personal name

Organization

Ministry of Education, Culture, Sports, Science and Technology

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

National Hospital Organization Kyushu Cancer Center

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

九州大学病院（福岡県）、九州がんセンター（福岡県）

Date of disclosure of the study information

2015

Year

06

Month

10

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

12

Month

03

Day

Date of IRB

Anticipated trial start date

2015

Year

04

Month

01

Day

Last follow-up date

2017

Year

02

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

06

Month

10

Day

Last modified on

2018

Year

06

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020689