Brain MetastasesPhase 1RAPIBENCT01551680
A Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib in Multiple Non Operable Brain Metastases
A Phase 1 study testing Radiation combined with iniparib (BSI-201) in people with Brain Metastases, run by Institut du Cancer de Montpellier - Val d'Aurelle at 3 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- Radiation combined with iniparib (BSI-201)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 3 sitesFrance
- Study dates
- Sep 2012to Feb 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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
- Brain metastases with severe intracranial hypertension clinical signs
- Other cancer except the known primary tumor or in situ cervix cancer or basocellular carcinoma
Who cannot join
- Anterior treatment for brain metastases (surgery, radiosurgery, stereotaxie)
- Leptomeningeal metastases
Trial locations and contacts
3 sites in 1 country.
France3 sites
CRLC Val d'Aurelle-Paul Lamarque
Montpellier, 34298
AP-HP Hôpital Saint-Louis
Paris
Institut Gustave-Roussy
Villejuif
About this study
Official title: A Phase I Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib (BSI-201) in Multiple Non Operable Brain Metastases
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
- Being tested
- Radiation combined with iniparib (BSI-201)
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Concurrent whole brain radiotherapy and iniparib | Experimental | Not described Receives: Radiation: Radiation combined with iniparib (BSI-201) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Until 12 week follow-up
Secondary outcomes (6)
Rate of adverse events
To evaluate toxicity later than 12 weeks after the end of radiotherapy and iniparib
Measured: Until 6 month follow-up
Quality of life
Quality of life will be assessed according to the EORTC QLQ-C30 and QLQ-BN20 questionnaires
Measured: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
Cognitive functions
Cognitive functions will be assessed according to the MMS (Mini Mental State) questionnaire
Measured: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
Objective response rate
Objective response rates (complete and partial response) will be evaluated by MRI according to the RECIST criteria (v1.1)
Measured: At 6 and 12 weeks after the end of radiotherapy
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.
Measured: 6 months
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2012 (estimated)
- Study startSep 2012
- Primary completionFeb 2014
- Study completionFeb 2014
Why it stopped: end of study of this product
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by Institut du Cancer de Montpellier - Val d'AurelleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Concurrent whole brain radiotherapy and iniparib
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Azria, MD, PhD, Principal investigator, CRLC Val d'Aurelle-Paul Lamarque
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01551680
- Sponsor's protocol ID
- RAPIBE
- Other IDs
- 2011-003772-36
- Acronym
- RAPIBE
- Status last verified
- Feb 2025
- First submitted
- 10 Feb 2012
- Last updated
- 13 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib (BSI-201) in Multiple Non Operable Brain Metastases
- ClinicalTrials.gov ID
- NCT01551680
- Acronym / sponsor ID
- RAPIBE / RAPIBE
- Conditions
- Brain Metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: end of study of this product
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Institut du Cancer de Montpellier - Val d'AurelleUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 13 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Concurrent whole brain radiotherapy and iniparib
| Arm | Type | Receives |
|---|---|---|
| Concurrent whole brain radiotherapy and iniparib | Experimental | Radiation: Radiation combined with iniparib (BSI-201) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (2 listed)
- Anterior treatment for brain metastases (surgery, radiosurgery, stereotaxie)
- Leptomeningeal metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Radiation | Concurrent whole brain radiotherapy and iniparib |
Primary outcome
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)
6 secondary outcomes
Rate of adverse events
Time frame: Until 6 month follow-up
Quality of life
Time frame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
Cognitive functions
Time frame: At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6
Objective response rate
Time frame: At 6 and 12 weeks after the end of radiotherapy
Time to local progression
Time frame: 6 months
Local progression-free survival
Time frame: 6 months
Results and safety
The study was stopped early (reason given: end of study of this product). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Azria, MD, PhD principal investigator
CRLC Val d'Aurelle-Paul Lamarque
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Radiation combined with iniparib (BSI-201) in people with Brain Metastases, run by Institut du Cancer de Montpellier - Val d'Aurelle at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: end of study of this product). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the Maximum Tolerated Dose (MTD) (time frame: Until 12 week follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025.