A Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib in Multiple Non Operable Brain Metastases (RAPIBE)
Recent pre-clinical and clinical data have indicated that BSI-201 does not possess characteristics typical of the PARP inhibitor class. Based on the results from in vitro and in vivo studies, this trial aims to evaluate the combination of BSI-201 concomitantly with radiotherapy in patients who present with multiple non operable brain metastases. As radiotherapy is a local treatment targeting only the tumor, and because the molecule BSI-201 has shown no major toxicity against tissues without DNA alterations, the proposed combination is expected to provide tumor-selective therapy and leading to a clinical benefit improvement.
Primary objective is to determine the recommended phase II dose (RP2D) and evaluate acute toxicity (CTC-AE v4.0 grading scale) of concurrent administration of whole brain radiotherapy (WBR) and a small molecule BSI-201 in non operable brain metastases.
|Brain Metastases||Radiation: Radiation combined with iniparib (BSI-201)||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib (BSI-201) in Multiple Non Operable Brain Metastases|
- To determine the Maximum Tolerated Dose (MTD) [ Time Frame: Until 12 week follow-up ]The MTD is defined as the dose level at which the Dose Limiting Toxicity (DLT) is observed in more than 20% of patients. The DLT is defined as: Any treatment-related toxicity CTC v4.0 ≥ grade 3(CTC-AE v4.0 grading scale)
- Rate of adverse events [ Time Frame: Until 6 month follow-up ]To evaluate toxicity later than 12 weeks after the end of radiotherapy and iniparib
- Quality of life [ Time Frame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6 ]Quality of life will be assessed according to the EORTC QLQ-C30 and QLQ-BN20 questionnaires
- Cognitive functions [ Time Frame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6 ]Cognitive functions will be assessed according to the MMS (Mini Mental State) questionnaire
- Objective response rate [ Time Frame: At 6 and 12 weeks after the end of radiotherapy ]Objective response rates (complete and partial response) will be evaluated by MRI according to the RECIST criteria (v1.1)
- Time to local progression [ Time Frame: 6 months ]Time to local progression will be measured from the start of treatment until the first date of objectively documented local progression.
- Local progression-free survival [ Time Frame: 6 months ]Local progression-free-survival will be measured from the start of treatment until the first date of objectively documented local progression or death.
|Study Start Date:||September 2012|
|Study Completion Date:||February 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
|Experimental: Concurrent whole brain radiotherapy and iniparib||
Radiation: Radiation combined with iniparib (BSI-201)
Dose escalation of iniparib is implemented according to the CRML method. Three patients will be included at the first dose level (2.8 mg/kg). As long as no DLT is observed, escalation will proceed in cohorts of three patients at least included at the next dose levels (4, 5.6, 8, 11.2 mg/kg). Once a DLT is observed, the CRML will be activated and will be used until the MTD has been found or until six patients have been treated at the highest dose level (11.2 mg/kg). A dose level of 2.0 mg/kg (dose level -1) is included in case the first dose level at 2.8 mg/kg is found to be the MTD.
Iniparib is given by iv infusion over 1 hour twice weekly. BSI 201 will start the week before the beginning of radiotherapy (W1) and will be continued during the entire irradiation (W2, W3, W4). It will be stopped after 8 injections.
RT is delivered five days a week over 3 weeks (W2, W3, W4) up to a total dose of 37.5 Gy. Each fraction delivers 2.5 Gy by two opposed tangential fields.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01551680
|CRLC Val d'Aurelle-Paul Lamarque|
|Montpellier, France, 34298|
|AP-HP Hôpital Saint-Louis|
|Principal Investigator:||David Azria, MD, PhD||CRLC Val d'Aurelle-Paul Lamarque|