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

NCT01551680 | Terminated Phase 1 DMC

• 2 other identifiers: RAPIBE2011-003772-36
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Rate of adverse events

  Until 6 month follow-up

• Quality of life

  At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6

• Cognitive functions

  At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6

• Objective response rate

  At 6 and 12 weeks after the end of radiotherapy

• Time to local progression

  6 months

Study Arms (1)

Concurrent whole brain radiotherapy and iniparib

EXPERIMENTAL

Radiation: Radiation combined with iniparib (BSI-201)

Interventions

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.

Concurrent whole brain radiotherapy and iniparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (3)

CRLC Val d'Aurelle-Paul Lamarque

Montpellier, 34298, France

Location

AP-HP Hôpital Saint-Louis

Paris, France

Location

Institut Gustave-Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

iniparib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• David Azria, MD, PhD

  CRLC Val d'Aurelle-Paul Lamarque

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Concurrent whole brain radiotherapy and iniparib
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Concurrent whole brain radiotherapy and iniparib

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: March 13, 2012
• Study Start: September 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

FR (3)