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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01551680
Recruitment Status : Terminated (end of study of this product)
First Posted : March 13, 2012
Last Update Posted : August 21, 2017
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

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.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : September 2012
Actual Primary Completion Date : February 2014
Actual Study Completion Date : February 2014

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. To determine the Maximum Tolerated Dose (MTD) [ Time Frame: Until 12 week follow-up ]
    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 :
  1. Rate of adverse events [ Time Frame: Until 6 month follow-up ]
    To evaluate toxicity later than 12 weeks after the end of radiotherapy and iniparib

  2. Quality of life [ Time Frame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6 ]
    Quality of life will be assessed according to the EORTC QLQ-C30 and QLQ-BN20 questionnaires

  3. Cognitive functions [ Time Frame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6 ]
    Cognitive functions will be assessed according to the MMS (Mini Mental State) questionnaire

  4. Objective response rate [ Time Frame: At 6 and 12 weeks after the end of radiotherapy ]
    Objective response rates (complete and partial response) will be evaluated by MRI according to the RECIST criteria (v1.1)

  5. Time to local progression [ Time Frame: 6 months ]
    Time to local progression will be measured from the start of treatment until the first date of objectively documented local progression.

  6. Local progression-free survival [ Time Frame: 6 months ]
    Local progression-free-survival will be measured from the start of treatment until the first date of objectively documented local progression or death.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01551680

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CRLC Val d'Aurelle-Paul Lamarque
Montpellier, France, 34298
AP-HP Hôpital Saint-Louis
Paris, France
Institut Gustave-Roussy
Villejuif, France
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
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Principal Investigator: David Azria, MD, PhD CRLC Val d'Aurelle-Paul Lamarque

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Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle Identifier: NCT01551680    
Other Study ID Numbers: RAPIBE
2011-003772-36 ( EudraCT Number )
First Posted: March 13, 2012    Key Record Dates
Last Update Posted: August 21, 2017
Last Verified: August 2017
Additional relevant MeSH terms:
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Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents