Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy

Phase 3

• Conditions: Bladder Cancer; Ureter Cancer; Transitional Cell Carcinoma
• Interventions: Drug: pemetrexed; Drug: Folic Acid; Drug: Vitamin B12 Injection; Drug: Dexamethasone

• Registration Number: NCT03193788
• Lead Sponsor: Asan Medical Center

Brief Summary

This study aims to verify superiority of pemetrexed maintenance to observation for patient without disease progression after 1 st line cisplatin-based chemotherapy.

Detailed Description

Patients with unresectable locally advanced, recurrent, or metastatic urothelial carcinoma of bladder, ureter, or renal pelvis who do not experience disease progression after 4 to 6 cycles of 1 st line chemotherapy administration.

After completion of 4-6 cycles, patients without disease progression on CT which is taken within 3 weeks after administration of the last chemotherapy will be randomized within 4 weeks after administration of the last chemotherapy to assign either maintenance group or observation group.

Pemetrexed 500 mg/m 2 mixed in normal saline 100 mL as a 10 minute IV infusion on day 1 of each 21 day cycle, with vitamin supplementation (folic acid 1000μg daily orally from 7 days prior to treatment initiation and vitamin B12 1000 μg IM 7 days prior to treatment initiation and then every 3 cycles). Thereafter, vitamin B12 can be injected on the same day of pemetrexed infusion. Dexamethasone 4 mg orally twice daily for 3 days beginning the day before treatment to minimize cutaneous reactions.

Treatment continues until occurrence of disease progression or intolerable toxicities upto maximum of 16 cycles.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-08-13
• Study Start: 2017-01
• Status Verified: 2017-05
• Study First Submitted QC: 2017-06-18
• Last Update Submitted: 2017-06-18
• Study First Posted: 2017-06-21
• Last Update Posted: 2017-06-21
• Primary Completion: 2019-12
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

1. Histologically or cytologically confirmation urothelial cancer of bladder, ureter, or renal pelvis.
2. Patients must present with locally advanced, recurrent or metastatic disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent.
3. Patients who were administered 4-6 cycles of cisplatin-based first line chemotherapy [GP (gemcitabine/cisplatin), classic MVAC (methotrexate/vinblastine/doxorubicin/cisplatin), or dose-dense MVAC] and were planned to undergo regular surveillance
4. ce after confirmation of absence of disease progression on CT taken within 3 week after the administration of the last cycle of 1st line chemotherapy.
5. For patients with recurrent disease who received prior adjuvant or neoadjuvant chemotherapy with cisplatin-containing regimen, the last administration of previous treatment should be administered at least 6 months before start date of 1st line chemotherapy.
6. Measurable disease according RECIST criteria v 1.1.
7. Age 20 years or older
8. ECOG performance status 2 or better
9. Adequate bone marrow, hepatic, and renal function
10. Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment

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Exclusion Criteria

1. Prior systemic chemotherapy or immunotherapy for palliative aim before or after 1st line cisplatin-based chemotherapy. However, prior intravesical chemotherapy or immunotherapy is allowed.
2. Disease progression during or after 1st line cisplatin-based chemotherapy
3. Known CNS metastasis
4. Diagnosis of any serious secondary malignancy within the last 2 years, except for adequately treated basal cell or squamous cell carcinoma of skin, early gastric carcinoma, early stage thyroid carcinoma, insignificant prostate carcinoma, or in situ carcinoma of cervix uteri
5. Pregnancy or breast feeding.
6. Serious hypersensitivity reaction to pemetrexed.
7. Severe renal function impairment with creatinine clearance <45 mL/min by standard Cockcroft-Gault formula or GFR measured by Tc99m-DPTA serum clearance method.
8. Other severe acute or chronic medical or psychiatric condition

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
pemetrexed maintenance	Vitamin B12 Injection	Drug: Pemetrexed Maintenance therapy: 500 mg/m\^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation. Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment
pemetrexed maintenance	Folic Acid	Drug: Pemetrexed Maintenance therapy: 500 mg/m\^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation. Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment
pemetrexed maintenance	pemetrexed	Drug: Pemetrexed Maintenance therapy: 500 mg/m\^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation. Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment
pemetrexed maintenance	Dexamethasone	Drug: Pemetrexed Maintenance therapy: 500 mg/m\^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation. Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment

Primary Outcome Measures

Name	Time	Method
progression free survival	Every 9 weeks, from date of randomization until the date of first documented progression upto 24 months	Time between randomization and disease progression or death from any causes, whichever came first. Alive patients free of progression will be censored at the last follow-up

Secondary Outcome Measures

Name	Time	Method
objective response rate	every 9 weeks, assess the best overall response from date of randomization until the date of first documented progression upto 24 months	Objective response rate will be measured according to RECIST 1.1
Incidence of treatment-emergent adverse events	every 3 weeks for pemetrexed group, every 9 weeks for observation group from date of randomization until the date of first documented progression upto 24 months	Safety assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
overall survival	From date of randomization until the date of death from any cause, assessed up to 1 year after the end of treatment	Time interval between randomization and death (all causes). Alive patients will be censored at the last date of news or data cut off
Quality of Life	before randomization, then 9, 18, and 27 weeks after randomization	QoL will be assessed by EORTC QLQ-C30 core questionaire

Trial Locations

Locations (21)

Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of

Dong-A University Medical Center; 🇰🇷 Pusan, Korea, Republic of

Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine; 🇰🇷 Seoul, Korea, Republic of

Fatima Hospital; 🇰🇷 Daegu, Korea, Republic of

Inje University Sanggye Paik Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

St. Vincent's Hospital, The Catholic University of Korea; 🇰🇷 Suwon, Korea, Republic of

Yonsei Cancer Center; 🇰🇷 Seoul, Korea, Republic of

Uijeongbu St Mary's hospital, Catholic university of Korea; 🇰🇷 Uijeongbu, Korea, Republic of

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Korea, Republic of

Keimyeong University Dongsan Medical Center; 🇰🇷 Daegu, Korea, Republic of

Hallym University Medical Center, Hallym University College of Medicine; 🇰🇷 Anyang, Korea, Republic of

Chungnam University Hospital; 🇰🇷 Daejeon, Korea, Republic of

Hallym University Dongtan Sacred Heart Hospital; 🇰🇷 Hwaseong-si, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Chung Ang University Hospital; 🇰🇷 Seoul, Korea, Republic of

National Health Insurance Service Ilsan Hospital; 🇰🇷 Goyang, Korea, Republic of

Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; 🇰🇷 Seoul, Korea, Republic of

Inje University Haeundae Paik Hospital; 🇰🇷 Pusan, Korea, Republic of

Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea; 🇰🇷 Seoul, Korea, Republic of

Pusan National University Hospital, Pusan National University School of Medicine; 🇰🇷 Pusan, Korea, Republic of