Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 10:01 PM
Ignite Modification Date:
2025-12-24 @ 10:01 PM
NCT ID:
NCT01202032
Brief Summary:
This is an open-label, multicenter dose-escalation phase I study using a 3+3+3 design (i.e., 3 to 9 patients per dose level) in patients with mRCC or others advanced refractory solid tumors. Enrolment will be performed to include approximately ½ of patients with mRCC.
The primary endpoint is the occurrence of limiting toxicities leading to definitive discontinuation of the study drugs during the first 24 weeks in absence of progression of the disease.
Secondary endpoints included the occurrence of Dose Limiting Toxicities (DLTs) evaluated during the first two cycles; overall response rate, 6-months progression-free survival rate and Pharmacokinetic assessments.
Detailed Description:
The primary endpoint is the occurrence of limiting toxicities leading to definitive discontinuation of the study drugs during the first 24 weeks in absence of progression of the disease.
Secondary endpoints included the occurrence of Dose Limiting Toxicities (DLTs) evaluated during the first two cycles; overall response rate (ORR), 6-months progression-free survival rate and Pharmacokinetic assessments.
The following definitions will be used:
DLT:
The Dose Limiting Toxicities (DLTs) are defined as the occurrence during the first two cycles of any grade 4 toxicity, and of any following events:
* clinical evidence of congestive heart failure,
* any arterial thromboembolic event,
* grade 3 venous thrombosis,
* grade 3 thrombocytopenia \>=7 days or associated with bleeding,
* grade 3 hypertension uncontrolled (\>=160/90 mmHg) with medications,
* grade 3 elevations in AST/ALT or total bilirubin. Any other grade 3 toxicity \>=7 days is also considered as a DLT, with exception of fatigue.
MTD:
The determination of the maximum-tolerated dose (MTD) will be conducted on a 3 + 3 + 3 design. Cohorts of 3 to 9 patients will be sequentially enrolled in 3 steps to receive one of four escalated doses of Pazopanib in combination with Bevacizumab to establish the MTD (step 1: patients 1 to 3; step 2: patients 4 to 6; step 3: patients 7 to 9).
The MTD is considered to be exceeded if DLT is observed during the first 2 cycles (i.e., 56 days) in at least 2 out of 3 or 3 out of 6 patients evaluable for MTD in the two first steps, then in at least 3 out of 9 patients after completion of enrolment (step 3).
When the MTD will be established, patients already involved in the follow-up phase at a dose level above the MTD should decrease to the MTD.
Note: in an exploratory way (i.e., with simulation) the possibility to take into account for the determination of the MTD the occurrence of recurrent grade 2 events or the combination of synergic grade 2-3 toxicities as "1/2 DLT" will be investigated in the study.
Optimal Long Exposure Dose (OLED):
To determine the Optimal Long Exposure Dose (OLED), all patients which will not experience a Dose Limiting Toxicity (DLT) during the first two cycles will continue the treatment and will be followed until week 24, in order to record toxic reactions of lesser severity or mixed toxicities leading to definitive discontinuation of the study drug, in the absence of progression of the disease.
The OLED is defined as the dose level (less than or equal to the MTD) for which the occurrence of sub-acute limiting toxicities leading to definitive discontinuation of the study drug is compatible with further phase II studies.
In practice, if \<=2/7-8 patients or \<=3/9 patients treated at a dose level \<=MTD and followed until week 24 experience sub-acute limiting toxicities, that dose level will be considered as the OLED.
ORR:
The overall response rate (ORR) is defined as the proportion of patients with a complete response (CR) or partial response (PR) - target lesions and tumor response according to RECIST guidelines.
Progression-Free Survival (PFS):
Progression-free survival (PFS) is defined as the time from the date of first study drug administration to the date of the first observation of documented disease progression or death due to any cause. PFS will be determined based on tumor assessment (RECIST criteria) and survival information.
Study:
NCT01202032
Study Brief:
Protocol Section:
NCT01202032