Pemetrexed Plus Cisplatin Bi-Weekly, in Patients With Urothelial Cancer (Metastatic, Locally Advanced or Non-Resectable)

• ClinicalTrials.gov Identifier: NCT00374868
• Recruitment Status: Completed
• First Posted: September 12, 2006
• Results First Posted: June 17, 2009
• Last Update Posted: November 4, 2010
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

Brief Summary:

To assess the anti-tumor activity, as measured by response rate to bi-weekly pemetrexed plus cisplatin, in chemo-naive patients with diagnosed metastatic or locally advanced (non-resectable) urothelial cancer.

Condition or disease	Intervention/treatment	Phase
Urologic Neoplasms	Drug: pemetrexed; Drug: cisplatin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 59 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of Biweekly ALIMTA Plus Cisplatin in Patients With Locally, Advanced, Non-Resectable or Metastatic Urothelial Cancer
• Study Start Date: August 2006
• Actual Primary Completion Date: April 2008
• Actual Study Completion Date: April 2008

Arms and Interventions

Arm

Intervention/treatment

Experimental: Pemetrexed + Cisplatin

Drug: pemetrexed; Phase 1: 300 mg/m^2, intravenous (IV), days 1 and 15 every 28 days x 2 cycles (dose escalation: 300 mg/m^2, 400 mg/m^2, and 500 mg/m^2) Phase 2: phase 1 determined dose, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy; Other Names: LY231514; Alimta; Drug: cisplatin; Phase 1: 50 mg/m^2, intravenous (IV), days 1 and 15 every 28 days x 2 cycles Phase 2: 50 mg/m^2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy

Outcome Measures

Primary Outcome Measures :

1. Best Overall Tumor Response [ Time Frame: baseline to measured progressive disease (up to 620 days) ]
   Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.

Secondary Outcome Measures :

1. Time to Response [ Time Frame: baseline to response (up to 620 days) ]
   Defined as time from study enrollment to the first Complete Response or Partial Response (using RECIST criteria). Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
2. Duration of Response [ Time Frame: time of response to progressive disease (up to 620 days) ]
   The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
3. Duration of Stable Disease [ Time Frame: time of no response or progression (up to 620 days) ]
   Defined as time from study enrollment to the first progression of disease, complete response, partial response, or death from any cause. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.
4. Time to Progressive Disease [ Time Frame: baseline to measured progressive disease (up to 620 days) ]
   Defined as the time from study enrollment to the first date of disease progression. Time to disease progression was censored at the date of death if death was due to other cause. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions.
5. Time to Treatment Failure (TTF) [ Time Frame: baseline to stopping treatment (up to 620 days) ]
   Time from study enrollment to first observation of disease progression, death from any cause, or early discontinuation of treatment (including toxicity or if patient had stable disease after 4 cycles). TTF was censored at date of last follow-up visit for patients who did not discontinue early, who were still alive, and who had not progressed.
6. Progression-Free Survival [ Time Frame: baseline to measured progressive disease (up to 620 days) ]
   Defined as the time from study enrollment until disease progression or death from any cause.
7. Overall Survival [ Time Frame: baseline to date of death from any cause (up to 620 days) ]
   Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically proven locally advanced disease or metastatic transitional cell carcinoma of the urothelium including bladder, urethra, ureter, and renal pelvis. Patients should not be suitable for surgery or radiation with curative intent. However patients whose pre-chemotherapy sites of disease are restricted to the primary or regional lymph node sites and who have a major response to chemotherapy will be evaluated for post-chemotherapy surgical resection of residual cancer if the tumor has become resectable at the end of chemotherapy.
• Measurable disease status, as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Therasse et al., 2000)
• One course of prior radiation therapy is allowed. Prior radiation must have been completed at least 4 weeks before enrolment into the study and the patients must have recovered from all toxic effects.

Exclusion Criteria:

• Have central nervous system (CNS) or leptomeningeal metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography (CT) or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required.
• Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents 2 days before, the day of, and 2 days after the dose of pemetrexed plus cisplatin or cisplatin alone. If a patient is taking a nonsteroidal anti-inflammatory drug (NSAID) or salicylate with a long half-life (for example, naproxen, piroxicam, diflunisal) it should not be taken 5 days before the dose of pemetrexed (8-day period for long-acting agents such as piroxicam), the day of, and 2 days after the dose of pemetrexed plus cisplatin.

Contacts and Locations

Locations

Spain

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Barcelona, Spain, 08035

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Madrid, Spain, 28041

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Pamplona, Spain, 31008

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Sabadell, Spain, 08208

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Santander, Spain, 39008

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00374868
• Other Study ID Numbers: 8679; H3E-ES-S085 ( Other Identifier: Eli Lilly and Company )
• First Posted: September 12, 2006
• Results First Posted: June 17, 2009
• Last Update Posted: November 4, 2010
• Last Verified: October 2010

Additional relevant MeSH terms:

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors