UMIN-CTR Clinical Trial

Public title

Phase I/II Study of Topotecan and Ifosfamide in Pediatric Patients with Relapsed or Refractory Solid Tumors

Acronym

TI chemotherapy for Relapsed Pediatric Solid Tumor pI/II

Scientific Title

Phase I/II Study of Topotecan and Ifosfamide in Pediatric Patients with Relapsed or Refractory Solid Tumors

Scientific Title:Acronym

TI chemotherapy for Relapsed Pediatric Solid Tumor pI/II

Region

Japan

Condition

Relapse/ refractory pediatric solid tumor

Classification by specialty

Pediatrics

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

1. To determine the maximum tolerated dose of topotecan when administered in combination with ifosfamide in pediatric patients with relapsed or primary refractory solid tumors
2. To determine the safety and efficacy of this regimen at the recommended dosage
3. To characterize the pharmacokinetics of topotecan in combination with ifosfamide in pediatric patients

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I,II

Primary outcomes

Phase I: MTD
Phase II: probability of the patients who can tolerate more than 4 courses of chemotherapy at the recommended dosage

Key secondary outcomes

Phase I: incidence of dose limiting toxicity etc.
Phase II: progression free survival, overall survival etc.

Study type

Interventional

Basic design

Single arm

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

TI chemotherpay in which ifosfamide IV over 1 hours followed by topotecan IV over 2 hours on days 1-5, to be repeated every 3 weeks

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

1

years-old

<=

Age-upper limit

30

years-old

>=

Gender

Male and Female

Key inclusion criteria

1. neuroblastoma, rhabdomyosarcoma, undifferentiated sarcoma, Ewing's sarcoma family of tumor, retinoblastoma, Wilm's tumor, hepatoblastoma, osteosarcoma, other bone or tissue malignant tumor, meduloblastoma
2. relapse or progression following disease specific first-line standard chemotherapies
3. <= 20 courses prior chemotherapy
4. no or 5 years > prior allogenic stem cell transplantation
5. no prior topotecan containing chemotherapy
6. > 21 days since prior antitumor cytotoxic agents
7. > 21 days since prior radiation therapy
8. > 14 days since prior surgery (containing open biopsy)
9. evidence of progression in clinical signs or symptoms or on imaging studies
10. 0-2 in ECOG PS
11. no signs or symptoms equivalent to CTC-AE Grade3 neurology adverse events
12. confirming the following laboratory results within 14 days
(1) Absolute neutrophil count >= 1,000/mm~3 (at least 4days since prior G-CSF administration)
(2) Platelet count >= 75,000/mm~3 (platelet transfusions allowed)
(3) serum total Bilirubin <= 1.2mg/dl
(4) ALT <= 100 IU/l
(5) serum Potassium >= 3.0mmol/l
(6) Creatinine adjusted according to age as follows:
<= 0.6 mg/dl (1 year-23 months)
<= 0.8 mg/dl (2 years-5 years)
<= 0.9 mg/dl (6 years-9 years)
<= 1.1 mg/dl (10 years-12 years [male])
<= 1.0 mg/dl (10 years-12 years [female])
<= 1.5 mg/dl (13 years-15 years [male])
<= 1.2 mg/dl (13 years and over [female])
<= 1.7 mg/dl (16 years and over [male])

13. no episode of Status Epilepticus or at least 22 days since last episode of Status Epilepticus
14. no episode of Status Epilepticus within 48 hours after administration of ifosfamide
15. legal adult: Written informed consent
16. 16 years and over, but, no legal adult: written informed consent from both patient and legal guardian
17. 15 years and under: written informed consent from legal guardian

Key exclusion criteria

1. Active double cancer (synchronous double cancer and metachronous double cancer within 5 disease-free years), excluding carcinoma in situ (lesions equal to intraepithelial or intramucosal cancer) judged to have been cured with local treatment
2. Active infection requiring systemic medication
3. abnormality in electrocardiogram tested within 28 days, requiring intervention
4. respiratory or heart disorder requiring oxygen supply, except from malignant pleural effusion
5. abnormality in electroencephalogram and requiring medication for neuropsychological signs or symptoms
6. Women during pregnancy or breast-feeding
7. Psychosis
8. Systemic steroids medication

Target sample size

40

Name of lead principal investigator

1st name
Middle name
Last name	Atsushi Ogawa

Organization

Niigata Cancer Center Hospital

Division name

Pediatric Division

Zip code

Address

2-15-3 Kawagishi-cho, Chuo-ku, Niigata 951-8566, Japan

TEL

025-266-5111

Email

atsushi@niigata-cc.jp

Name of contact person

1st name
Middle name
Last name	Hiroshi Kawamoto

Organization

study coordinator

Division name

National Cancer Center Hospital

Zip code

Address

15-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

TEL

03-3542-2511

Homepage URL

http://www.nposuccess.jp/datacenter/about_ti.html

Email

hkawamot@ncc.go.jp

Institute

Group for "making evidence for the drugs which are available in clinical practice in Europe and USA but not available in Japan"

Institute

Department

Personal name

Organization

Ministry of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

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

国立がん研究センター中央病院（東京都）
日本大学医学部附属板橋病院（東京都）
静岡県立静岡がんセンター（静岡県）
新潟県立がんセンター新潟病院（新潟県）
大阪市立総合医療センター（大阪府）
滋賀医科大学附属病院（滋賀県）
国立病院機構九州がんセンター（福岡）
兵庫県立こども病院（兵庫）

Date of disclosure of the study information

2008

Year

02

Month

16

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=42685

Number of participants that the trial has enrolled

Results

Recommended dose of topotecan with ifosfamide 1.2g/m2/d was determined to be level0. Currently phaseII is ongoing.

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

2007

Year

12

Month

28

Day

Date of IRB

Anticipated trial start date

2008

Year

02

Month

01

Day

Last follow-up date

2013

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2008

Year

02

Month

16

Day

Last modified on

2014

Year

02

Month

10

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001245