A Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib in Multiple Non Operable Brain Metastases

NCT ID: NCT01551680

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2014-02-28

Brief Summary

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.

Conditions

Brain Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Concurrent whole brain radiotherapy and iniparib

Group Type: EXPERIMENTAL

Radiation combined with iniparib (BSI-201)

Intervention Type: 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.

Interventions

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.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Non operable brain metastases from any type of cancer (≥ 2)
• At least one measured brain target available ≥ 1 cm (T1-weighted sequences with contrast application MRI)
• No stereotaxie indication
• Any anterior treatments for systemic disease (any chemotherapy at any line) are accepted but have to be interrupted at least 15 days before and up to 30 days after the present protocol
• No extra-brain disease or stabilized since at least 1 month
• Aged ≥ 18 years old
• KPS > 70 (RPS class I or II)
• Adequate bone marrow function: WBC ≥ 3.5 x 109/L, ANC ≥ 1.5 x 109/L, Platelets ≥ LLN, Hb > 10g/dL,
• Adequate renal function: serum creatinine ≤ 1.5 × ULN and blood urea nitrogen ≤ 25 mg/dL
• Male or female patient using adequate contraceptive method
• Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the start of treatment
• Informed and signed consent
• Able to be followed according to the terms of the protocol
• Affiliated to the French National social security

Exclusion Criteria

• Anterior treatment for brain metastases (surgery, radiosurgery, stereotaxie)
• Leptomeningeal metastases
• Inclusion in another protocol within 30 days
• Brain metastases with severe intracranial hypertension clinical signs
• Other cancer except the known primary tumor or in situ cervix cancer or basocellular carcinoma

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut du Cancer de Montpellier - Val d'Aurelle

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Azria, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CRLC Val d'Aurelle-Paul Lamarque

Locations

CRLC Val d'Aurelle-Paul Lamarque

Montpellier, , France

AP-HP Hôpital Saint-Louis

Paris, , France

Institut Gustave-Roussy

Villejuif, , France

Countries

France

Other Identifiers

2011-003772-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RAPIBE

Identifier Type: -

Identifier Source: org_study_id