Neoplasm MalignantPhase 1NCT01455532
A Dose Escalation Study of Iniparib as a Single Agent and in Combination in Solid Tumors
A Phase 1 study testing Iniparib (SAR240550-BSI-201), Gemcitabine and Carboplatin in people with Neoplasm Malignant, run by Sanofi at 6 sites in United States.
Trial summary
Primary Objective: To assess the safety and the maximum tolerated dose(MTD) of iniparib as a single agent and in combination with chemotherapeutic regimens in patients with advanced solid tumors that are refractory to standard therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Malignant
- What is being tested?
- Iniparib (SAR240550-BSI-201), Gemcitabine and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 6 sitesUnited States
- Study dates
- Nov 2011to Apr 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
- Capable of understanding and complying with the protocol requirements, and have signed the informed consent document
- ≥18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- To have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease; that is refractory to standard therapy and/or therapies known to provide clinical benefit or for which no standard therapy exists
- For phase 1b, patients for whom the backbone chemotherapy (dose and schedule) can be considered as a standard therapeutic regime for their cancer.
- Have measurable disease or non-measurable disease, defined according to RECIST Version 1.1. Patients with skin only metastases are eligible, if the appropriate photography documentation (including measurement) of the skin metastases is provided.
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- Adequate organ and bone marrow function
- Willingness, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ an effective barrier method of contraception during the study drug administration and for a period of 6 months following the last dose.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment, and at least 6 months after the last dose of study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Sexually active men must agree to use a medically acceptable form of birth control during treatment and at least 6 months after the last dose. If a female partner becomes pregnant during course of study the treating physician should be informed immediately.
Who cannot join
- Systemic anticancer therapy within 14 days before the first dose of study drug.
- Known allergy or hypersensitivity to components of the iniparib, gemcitabine, paclitaxel, PLD,or carboplatin formulation.
- Not recovered to Grade ≤1 from adverse events (AE), per NCI-CTCAE Version 4.03 or to within 10% of pre-treatment baseline values, due to investigational drugs, radiation, or other medications administered more than 30 days before enrollment in this study. Alopecia at screening is not exclusionary.
- Prior radical (curative) radiation therapy for treatment of cancer ≥25% of the bone marrow (1). Prior radiation to the whole pelvis is not allowed. Prior radical radiotherapy must be completed at least 4 weeks before study entry.
- Patients who have received palliative radiation therapy for symptomatic metastases must have completed treatment ≥14 days prior to initiation of study treatment.
- Active brain metastases. Patients with treated brain metastases are eligible, if 1. Radiation therapy was completed at least 2 weeks prior to study treatment; 2. Follow-up scan shows no disease progression; and 3. Patient does not require steroids. Screening for brain metastases is not required if the patient is asymptomatic.
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- Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), including pre-existing ventricular arrhythmia or conduction abnormality requiring medication, or cardiomyopathy or history of a myocardial infarction within the last 6 months
- Other major medical condition (eg, uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) which the Investigator feels might compromise the patient's effective and safe participation in the trial.
- Pregnant or breastfeeding
- Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or Hepatitis C Antibodies (HCAb). Testing is not required unless circumstances warrant confirmation.
- Patients with acute or chronic leukemia or with any other disease likely to have a significant bone marrow infiltration (screening not required).
- Prior treatment with gemcitabine, carboplatin, paclitaxel, or Pegylated liposomal doxorubicin.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Investigational Site Number 840010
Augusta, Georgia, 30912
Investigational Site Number 840001
Cincinnati, Ohio, 45267-0542
Investigational Site Number 840004
Los Angeles, California, 90048
Investigational Site Number 840006
San Antonio, Texas, 78229
Investigational Site Number 840002
Scottsdale, Arizona, 85258
Investigational Site Number 840007
St Louis, Missouri, 63110
About this study
Official title: A Phase 1/1b Dose Escalation Study Evaluating Iniparib (BSI201/SAR240550) as a Single Agent and in Combination With Chemotherapeutic Regimens in Patients With Solid Tumors
Primary Objective:
- To assess the safety and the maximum tolerated dose(MTD) of iniparib as a single agent and in combination with chemotherapeutic regimens in patients with advanced solid tumors that are refractory to standard therapy.
Read more
Secondary Objectives:
- To assess the antitumor effect of iniparib (per Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease.
- To characterize iniparib (and its metabolites, if possible) pharmacokinetics.
Based on data generated by Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.
Read the detailed description
The duration of the study for an individual patient will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (3 weeks or 4 weeks depending on regimen) of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue until precluded by toxicity, progression, or death.
- Conditions
- Neoplasm Malignant
- Being tested
- Iniparib (SAR240550-BSI-201), Gemcitabine, Carboplatin, Placlitaxel, Pegylated liposomal doxorubicin
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iniparib (SAR240550-BSI-201)Drug
Pharmaceutical form:Solution for infusion
Route of administration: Intravenous
GemcitabineDrug
Pharmaceutical form:Solution for infusion
Route of administration: Intravenous
CarboplatinDrug
Pharmaceutical form:Solution for infusion
Route of administration: Intravenous
PlaclitaxelDrug
Pharmaceutical form:Solution for infusion
Route of administration: Intravenous
Pegylated liposomal doxorubicinDrug
Pharmaceutical form:Solution for infusion
Route of administration: Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Iniparib, single agent | Experimental | Iniparib will be initially administered intravenously once weekly (days 1, 8, and 15) for 3 weeks, in a 21-day cycle. Then, iniparib will be administered twice weekly (days 1, 4, 8, 11, 15, and 18) in a 21-day cycle. Cycle1 (day 1 thru day 21) will be defined as the dose limiting toxicities (DLT) observation period. Starting dose is 15 mg/kg once weekly. Receives: Drug: Iniparib (SAR240550-BSI-201) |
| Iniparib/Gemcitibine/Carboplatin | Experimental | Gemcitabine/carboplatin (GC) : Gemcitabine will be administered at 1,000 mg/m² as a 30min IV infusion and carboplatin area under the curve (AUC) 2 as a 60min IV infusion. Patients will receive gemcitabine/carboplatin infusions once weekly (days 1 and 8). Iniparib will be administered for two weeks, followed by a 1week of rest in a 21-day cycle (weekly schedule: days 1 and 8; twice weekly schedule: days: 1, 4, 8 and 11). Receives: Drug: Iniparib (SAR240550-BSI-201); Drug: Gemcitabine; Drug: Carboplatin |
| Iniparib/Paclitaxel | Experimental | Paclitaxel (P): Paclitaxel will be administered at the dose of 80 mg/m2 as a 60-minute intravenous infusion administered on days 1, 8, and 15 followed by a 1week of rest. Iniparib will be administered for three weeks, followed by 1week of rest in a 28-day cycle (weekly schedule: days 1, 8 and 15; twice weekly schedule: days 1, 4, 8, 11, 15 and 18). Receives: Drug: Iniparib (SAR240550-BSI-201); Drug: Placlitaxel |
| Iniparib/Pegylated liposomal doxorubicin/Carboplatin | Experimental | Pegylated liposomal doxorubicin (Doxil)/Carboplatin (PLD) : Doxil will be administered at 30 mg/m² as a 30min IV infusion and carboplatin AUC 4 as a 60min IV infusion on day 1 every four weeks. Iniparib will be administered for two weeks in a 28-day cycle (weekly schedule: days 1, and 8; twice weekly schedule: days 1, 4, 8, and 11). Receives: Drug: Iniparib (SAR240550-BSI-201); Drug: Carboplatin; Drug: Pegylated liposomal doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of iniparib as single agent and in combination with chemotherapeutic agents related dose limiting toxicities (DLTs) observed at first cycle
Measured: 3 - 4 weeks
Secondary outcomes (6)
To assess the antitumor effect of iniparib according to the Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease
Measured: Up to 2 years
Pharmakokinetic (PK) parameters: Cmax
Measured: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters : tmax
Measured: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters: tlast
Measured: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters: AUC
Measured: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters : t1/2z
Measured: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionMay 2013
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoplasm MalignantStudies of the same condition, open and under way.
- More trials run by SanofiThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01455532
- Sponsor's protocol ID
- TED11746
- Other IDs
- U1111-1118-6091
- Status last verified
- Oct 2014
- First submitted
- 7 Oct 2011
- Last updated
- 22 Oct 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Dose Escalation Study Evaluating Iniparib (BSI201/SAR240550) as a Single Agent and in Combination With Chemotherapeutic Regimens in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT01455532
- Acronym / sponsor ID
- TED11746
- Conditions
- Neoplasm Malignant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- May 2013 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 20 Oct 2011 (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.
Primary Objective:
- To assess the safety and the maximum tolerated dose(MTD) of iniparib as a single agent and in combination with chemotherapeutic regimens in patients with advanced solid tumors that are refractory to standard therapy.
Secondary Objectives:
- To assess the antitumor effect of iniparib (per Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease.
- To characterize iniparib (and its metabolites, if possible) pharmacokinetics.
Based on data generated by Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.
Detailed description
The duration of the study for an individual patient will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (3 weeks or 4 weeks depending on regimen) of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue until precluded by toxicity, progression, or death.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Iniparib, single agent | Experimental | Drug: Iniparib (SAR240550-BSI-201)Iniparib will be initially administered intravenously once weekly (days 1, 8, and 15) for 3 weeks, in a 21-day cycle. Then, iniparib will be administered twice weekly (days 1, 4, 8, 11, 15, and 18) in a 21-day cycle. Cycle1 (day 1 thru day 21) will be defined as the dose limiting toxicities (DLT) observation period. Starting dose is 15 mg/kg once weekly. |
| Iniparib/Gemcitibine/Carboplatin | Experimental | Drug: Iniparib (SAR240550-BSI-201), Drug: Gemcitabine, Drug: CarboplatinGemcitabine/carboplatin (GC) : Gemcitabine will be administered at 1,000 mg/m² as a 30min IV infusion and carboplatin area under the curve (AUC) 2 as a 60min IV infusion. Patients will receive gemcitabine/carboplatin infusions once weekly (days 1 and 8). Iniparib will be administered for two weeks, followed by a 1week of rest in a 21-day cycle (weekly schedule: days 1 and 8; twice weekly schedule: days: 1, 4, 8 and 11). |
| Iniparib/Paclitaxel | Experimental | Drug: Iniparib (SAR240550-BSI-201), Drug: PlaclitaxelPaclitaxel (P): Paclitaxel will be administered at the dose of 80 mg/m2 as a 60-minute intravenous infusion administered on days 1, 8, and 15 followed by a 1week of rest. Iniparib will be administered for three weeks, followed by 1week of rest in a 28-day cycle (weekly schedule: days 1, 8 and 15; twice weekly schedule: days 1, 4, 8, 11, 15 and 18). |
| Iniparib/Pegylated liposomal doxorubicin/Carboplatin | Experimental | Drug: Iniparib (SAR240550-BSI-201), Drug: Carboplatin, Drug: Pegylated liposomal doxorubicinPegylated liposomal doxorubicin (Doxil)/Carboplatin (PLD) : Doxil will be administered at 30 mg/m² as a 30min IV infusion and carboplatin AUC 4 as a 60min IV infusion on day 1 every four weeks. Iniparib will be administered for two weeks in a 28-day cycle (weekly schedule: days 1, and 8; twice weekly schedule: days 1, 4, 8, and 11). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Capable of understanding and complying with the protocol requirements, and have signed the informed consent document
- ≥18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- To have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease; that is refractory to standard therapy and/or therapies known to provide clinical benefit or for which no standard therapy exists
- For phase 1b, patients for whom the backbone chemotherapy (dose and schedule) can be considered as a standard therapeutic regime for their cancer.
Key exclusion criteria (13 listed)
- Systemic anticancer therapy within 14 days before the first dose of study drug.
- Known allergy or hypersensitivity to components of the iniparib, gemcitabine, paclitaxel, PLD,or carboplatin formulation.
- Not recovered to Grade ≤1 from adverse events (AE), per NCI-CTCAE Version 4.03 or to within 10% of pre-treatment baseline values, due to investigational drugs, radiation, or other medications administered more than 30 days before enrollment in this study. Alopecia at screening is not exclusionary.
- Prior radical (curative) radiation therapy for treatment of cancer ≥25% of the bone marrow (1). Prior radiation to the whole pelvis is not allowed. Prior radical radiotherapy must be completed at least 4 weeks before study entry.
- Patients who have received palliative radiation therapy for symptomatic metastases must have completed treatment ≥14 days prior to initiation of study treatment.
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 |
|---|---|---|
| Iniparib (SAR240550-BSI-201)Pharmaceutical form:Solution for infusion Route of administration: Intravenous | Drug | Iniparib, single agent, Iniparib/Gemcitibine/Carboplatin, Iniparib/Paclitaxel, Iniparib/Pegylated liposomal doxorubicin/Carboplatin |
| GemcitabinePharmaceutical form:Solution for infusion Route of administration: Intravenous | Drug | Iniparib/Gemcitibine/Carboplatin |
| CarboplatinPharmaceutical form:Solution for infusion Route of administration: Intravenous | Drug | Iniparib/Gemcitibine/Carboplatin, Iniparib/Pegylated liposomal doxorubicin/Carboplatin |
| PlaclitaxelPharmaceutical form:Solution for infusion Route of administration: Intravenous | Drug | Iniparib/Paclitaxel |
| Pegylated liposomal doxorubicinPharmaceutical form:Solution for infusion Route of administration: Intravenous | Drug | Iniparib/Pegylated liposomal doxorubicin/Carboplatin |
Primary outcome
Assessment of iniparib as single agent and in combination with chemotherapeutic agents related dose limiting toxicities (DLTs) observed at first cycle
Time frame: 3 - 4 weeks
6 secondary outcomes
To assess the antitumor effect of iniparib according to the Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease
Time frame: Up to 2 years
Pharmakokinetic (PK) parameters: Cmax
Time frame: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters : tmax
Time frame: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters: tlast
Time frame: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters: AUC
Time frame: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Pharmakokinetic (PK) parameters : t1/2z
Time frame: 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2014.
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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.
Clinical Sciences & Operations study director
Sanofi
6 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 Iniparib (SAR240550-BSI-201), Gemcitabine and Carboplatin in people with Neoplasm Malignant, run by Sanofi at 6 sites in United States.
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 9 inclusion and 13 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: finished, as of the sponsor's last update on 22 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Assessment of iniparib as single agent and in combination with chemotherapeutic agents related dose limiting toxicities (DLTs) observed at first cycle (time frame: 3 - 4 weeks). 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 22 Oct 2014.