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

Asan Medical Center

Status and phase: Unknown; Phase 3

Conditions: Bladder Cancer; Transitional Cell Carcinoma; Ureter Cancer

Treatments: Drug: Folic Acid; Drug: pemetrexed; Drug: Dexamethasone; Drug: Vitamin B12 Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT03193788

KCSG GU16-05

Details and patient eligibility

About

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

Full 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.

Enrollment: 74 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

pemetrexed maintenance

Experimental group

Description:

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

Treatment:

Drug: Vitamin B12 Injection

Drug: Dexamethasone

Drug: pemetrexed

Drug: Folic Acid

observation

No Intervention group

Description:

observation group will be observed with best supportive care until progressive disease