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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-003772-36 | EudraCT Number |
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end of study of this product
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Concurrent whole brain radiotherapy and iniparib | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiation combined with iniparib (BSI-201) | Radiation | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| To determine the Maximum Tolerated Dose (MTD) | 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) | Until 12 week follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of adverse events | To evaluate toxicity later than 12 weeks after the end of radiotherapy and iniparib | Until 6 month follow-up |
| Quality of life | Quality of life will be assessed according to the EORTC QLQ-C30 and QLQ-BN20 questionnaires |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Azria, MD, PhD | CRLC Val d'Aurelle-Paul Lamarque | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRLC Val d'Aurelle-Paul Lamarque | Montpellier | 34298 | France | |||
| AP-HP Hôpital Saint-Louis |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C090712 | iniparib |
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Concurrent whole brain radiotherapy and iniparib
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Concurrent whole brain radiotherapy and iniparib
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|
| At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6 |
| Cognitive functions | Cognitive functions will be assessed according to the MMS (Mini Mental State) questionnaire | At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6 |
| Objective response rate | Objective response rates (complete and partial response) will be evaluated by MRI according to the RECIST criteria (v1.1) | At 6 and 12 weeks after the end of radiotherapy |
| Time to local progression | Time to local progression will be measured from the start of treatment until the first date of objectively documented local progression. | 6 months |
| Local progression-free survival | Local progression-free-survival will be measured from the start of treatment until the first date of objectively documented local progression or death. | 6 months |
| Paris |
| France |
| Institut Gustave-Roussy | Villejuif | France |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |