Phase I Study of CBP501 and Cisplatin in Patients With Advanced Refractory Solid Tumors
The purpose of this research study is to find the answers to the following questions:
- What are the highest doses of CBP501 and cisplatin that can be safely administered as consecutive 2-hours and 1-hour infusions every 21 days?
- What are the side effects of the combination of CBP501 and cisplatin when given as an infusion every 21 days?
- What amount of CBP501 and cisplatin are found in the blood at certain times after it is given?
- Are there any substances in your blood or tumor that can tell us about tumor sensitivity to CBP501 and cisplatin?
- Will CBP501 given with cisplatin help to treat your cancer?
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Clinical and Pharmacokinetic Study of CBP501 and Cisplatin Every 3 Weeks in Patients With Advanced Refractory Solid Tumors|
- Dose Limiting Toxicity (DLT) during the first two treatment cycles [ Time Frame: 6 weeks ]
- Incidence and severity of adverse events and laboratory abnormalities, graded according to NCI-CTCAE version 3.0 [ Time Frame: During and at end of study ]
- Occurrence of Serious Adverse Events (SAEs) [ Time Frame: During and at end of study ]
- Occurrence of discontinuations due to treatment-related adverse events [ Time Frame: At end of study ]
- Serum concentrations of CBP501 and total and ultrafiltrate platinum to determine, via non-compartmental methods, Cmax, AUC, lz, t½, Cl and Vss. [ Time Frame: During and at end of study ]
- Evaluation of the relationship between administered dose and plasma pharmacokinetic parameters for CBP501 and cisplatin [ Time Frame: During and at end of study ]
- Objective tumor response assessed according to RECIST [ Time Frame: During and at end of study ]
- Time to progression [ Time Frame: During and at end of study ]
|Study Start Date:||November 2006|
|Study Completion Date:||May 2009|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
Experimental: CBP501 and Cisplatin
Dose escalation study
Drug: CBP501 and Cisplatin
CBP501 is given IV on Day 1 of each cycle (every 21 days). Dose escalation of CBP501 and cisplatin will be starting doses of 3.6 mg/m² CBP501 and 50 mg/m² cisplatin (Dose Level 1). Step 1, if during the first 2 cycles, at least 2 out of 3 to 6 patients experience Dose Limiting Toxicity (DLT) at 50 mg/m² cisplatin, then the cisplatin dose will be de-escalated to 30 mg/m². If no more than 1 out of 6 patients experiences DLT, cisplatin dose will be escalated to 75 mg/m². Step 2, dose escalation will be performed using the cisplatin MTD, with escalating CBP501 doses. CBP501 dose escalation will take place until the MTD has been defined or 74 mg/m² is reached.
Other Name: CBP501 and CDDP
9.1 23BOverall Study Design and Plan This was an open-label, multicenter, dose-escalation and pharmacokinetic Phase I study of CBP501 and cisplatin administered as consecutive IV infusions according to a once-every-3-weeks schedule in patients with advanced solid tumors refractory to standard therapy. The study was conducted in three US centers. During the course of the study, an amendment was introduced (#3, October 17th, 2007; see section X9.8X) to allow administration of a unique dosing of single agent CBP501 prior to the initiation of combination therapy to enable completion of the pharmacokinetic (PK) characterization of single agent CBP501. Pharmacodynamic analysis involving phosphoserine 216 evaluations was also removed. See section X16.1.1X for copies of the protocol and all protocol amendments. With 8 additional patients included at the recommended dose (at DL6), it was decided to stop all PK and CTC sampling (and therefore the day-7 CBP501 alone infusion), as sufficient information had been retrieved. In addition, based on evidence of efficacy observed in ovarian cancer patients, a further 10 ovarian and 4 endometrial cancer patients were to be included at the recommended dose; these patients were to be assessed for DLT to confirm the identification of the MTD.
Case Report Forms were used to collect the data, and data management was carried out by AAIOncology. All laboratory data and Investigator observations were be transcribed into the CRF. ECG, U/S, MRI and CT scans were to be reported in summary in the CRF. The original reports, traces and films were to be retained by the Investigators for future reference. See section X16.1.2X for a sample CRF.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00551512
|United States, Arizona|
|Scottsdale Clinical Research Institute|
|Scottsdale, Arizona, United States, 85258|
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Nevada|
|Nevada Cancer Institute|
|Las Vegas, Nevada, United States, 89135|
|Study Director:||Ernesto Wasserman, MD||AAIOncology|