Clinical trial NCT01551680: A Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib in Multiple Non Operable Brain Metastases
Official title: A Phase I Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib (BSI-201) in Multiple Non Operable Brain Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Brain Metastases
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
First posted: 2012-03-13
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Concurrent whole brain radiotherapy and iniparib
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: To determine the Maximum Tolerated Dose (MTD)
timeFrame: Until 12 week follow-up
Secondary outcomes:
measure: Rate of adverse events
timeFrame: Until 6 month follow-up
measure: Quality of life
timeFrame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
measure: Cognitive functions
timeFrame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
measure: Objective response rate
timeFrame: At 6 and 12 weeks after the end of radiotherapy
measure: Time to local progression
timeFrame: 6 months
measure: Local progression-free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CRLC Val d'Aurelle-Paul Lamarque
city: Paris
country: France
facility: AP-HP Hôpital Saint-Louis
city: Villejuif
country: France
facility: Institut Gustave-Roussy
Study officials:
affiliation: CRLC Val d'Aurelle-Paul Lamarque
name: David Azria, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: