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

Primary Purpose

Brain Metastases

Status
Terminated
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Radiation combined with iniparib (BSI-201)
Sponsored by
Institut du Cancer de Montpellier - Val d'Aurelle
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CRLC Val d'Aurelle-Paul Lamarque
  • AP-HP Hôpital Saint-Louis
  • Institut Gustave-Roussy

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Concurrent whole brain radiotherapy and iniparib

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Rate of adverse events
To evaluate toxicity later than 12 weeks after the end of radiotherapy and iniparib
Quality of life
Quality of life will be assessed according to the EORTC QLQ-C30 and QLQ-BN20 questionnaires
Cognitive functions
Cognitive functions will be assessed according to the MMS (Mini Mental State) questionnaire
Objective response rate
Objective response rates (complete and partial response) will be evaluated by MRI according to the RECIST criteria (v1.1)
Time to local progression
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
Local progression-free-survival will be measured from the start of treatment until the first date of objectively documented local progression or death.

Full Information

First Posted
February 10, 2012
Last Updated
August 16, 2017
Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
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1. Study Identification

Unique Protocol Identification Number
NCT01551680
Brief Title
A Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib in Multiple Non Operable Brain Metastases
Acronym
RAPIBE
Official Title
A Phase I Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib (BSI-201) in Multiple Non Operable Brain Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
end of study of this product
Study Start Date
September 2012 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Concurrent whole brain radiotherapy and iniparib
Arm Type
Experimental
Intervention Type
Radiation
Intervention Name(s)
Radiation combined with iniparib (BSI-201)
Intervention Description
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 Measure Information:
Title
To determine the Maximum Tolerated Dose (MTD)
Description
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)
Time Frame
Until 12 week follow-up
Secondary Outcome Measure Information:
Title
Rate of adverse events
Description
To evaluate toxicity later than 12 weeks after the end of radiotherapy and iniparib
Time Frame
Until 6 month follow-up
Title
Quality of life
Description
Quality of life will be assessed according to the EORTC QLQ-C30 and QLQ-BN20 questionnaires
Time Frame
At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
Title
Cognitive functions
Description
Cognitive functions will be assessed according to the MMS (Mini Mental State) questionnaire
Time Frame
At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
Title
Objective response rate
Description
Objective response rates (complete and partial response) will be evaluated by MRI according to the RECIST criteria (v1.1)
Time Frame
At 6 and 12 weeks after the end of radiotherapy
Title
Time to local progression
Description
Time to local progression will be measured from the start of treatment until the first date of objectively documented local progression.
Time Frame
6 months
Title
Local progression-free survival
Description
Local progression-free-survival will be measured from the start of treatment until the first date of objectively documented local progression or death.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Azria, MD, PhD
Organizational Affiliation
CRLC Val d'Aurelle-Paul Lamarque
Official's Role
Principal Investigator
Facility Information:
Facility Name
CRLC Val d'Aurelle-Paul Lamarque
City
Montpellier
ZIP/Postal Code
34298
Country
France
Facility Name
AP-HP Hôpital Saint-Louis
City
Paris
Country
France
Facility Name
Institut Gustave-Roussy
City
Villejuif
Country
France

12. IPD Sharing Statement

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

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