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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Centre Val d'Aurelle - Paul Lamarque
Sponsor:
Information provided by (Responsible Party):
Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier:
NCT01551680
First received: February 10, 2012
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Brain Metastases
Radiation: Radiation combined with iniparib (BSI-201)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Centre Val d'Aurelle - Paul Lamarque:

Primary Outcome Measures:
  • To determine the Maximum Tolerated Dose (MTD) [ Time Frame: Until 12 week follow-up ] [ Designated as safety issue: Yes ]
    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)


Secondary Outcome Measures:
  • Rate of adverse events [ Time Frame: Until 6 month follow-up ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Local progression-free-survival will be measured from the start of treatment until the first date of objectively documented local progression or death.


Estimated Enrollment: 30
Study Start Date: September 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01551680

Contacts
Contact: Jean-Pierre Bleuse, MD +33 4 67 61 23 44 Jean-Pierre.Bleuse@montpellier.unicancer.fr

Locations
France
CRLC Val d'Aurelle-Paul Lamarque Recruiting
Montpellier, France, 34298
Contact: David Azria, MD, PhD    + 33 4 67 61 85 79    David.Azria@montpellier.unicancer.fr   
Principal Investigator: David Azria, Pr         
AP-HP Hôpital Saint-Louis Recruiting
Paris, France
Contact: Christophe Hennequin, Pr         
Principal Investigator: Christophe Hennequin, Pr         
Institut Gustave-Roussy Recruiting
Villejuif, France
Contact: Céline Bourgier, Dr         
Principal Investigator: Céline Bourgier, Dr         
Sponsors and Collaborators
Centre Val d'Aurelle - Paul Lamarque
Investigators
Principal Investigator: David Azria, MD, PhD CRLC Val d'Aurelle-Paul Lamarque
  More Information

No publications provided

Responsible Party: Centre Val d'Aurelle - Paul Lamarque
ClinicalTrials.gov Identifier: NCT01551680     History of Changes
Other Study ID Numbers: RAPIBE, 2011-003772-36
Study First Received: February 10, 2012
Last Updated: February 4, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on August 26, 2014