CancerPhase 1NCT00268905
A Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors
A Phase 1 study testing E7389 + carboplatin AUC 5, E7389 + carboplatin AUC 6 and E7389+carboplatin AUC 6 in people with Cancer, run by Eisai Inc. at 11 sites in 3 countries.
Trial summary
The purpose of this study is to determine the maximum tolerated dose (MTD) and to explore the safety and anti-tumor activity of E7389 in combination with carboplatin in patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- E7389 + carboplatin AUC 5, E7389 + carboplatin AUC 6 and E7389+carboplatin AUC 6
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Oct 2006to Nov 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients ≥ 18 years of age.
- Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Patients with a life expectancy of ≥ three months.
- Patients with adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula.
- Patients with adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, hemoglobin ≥ 10.0 g/dL (this may have been corrected by transfusion or growth factors) and platelet count ≥ 100 × 10^9/L.
- Patients with adequate liver function as evidenced by bilirubin ≤ 1.5 mg/dL and alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limits of normal (ULN) (in the case of liver metastases ≤ 5 x ULN), unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase. to assess the liver function instead of the total alkaline phosphatase.
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- Patients willing and able to comply with the study protocol for the duration of the study.
- Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
- For patients in the dose finding phase, the following additional inclusion criteria must be fulfilled:
- Patients with pathologically diagnosed, histologically or cytologically confirmed advanced solid tumor, that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy).
- Patients with disease progression despite standard therapy or have disease for which no standard therapy exists.
- Patients with ≤ Grade 2 chemotherapy or radiation-related toxicities except alopecia.
- For NSCLC patients at the MTD, the following additional inclusion criteria must be fulfilled:
- Patients with pathologically diagnosed, histologically or cytologically confirmed advanced NSCLC (Stage IIIB or IV) with measurable disease, not amenable to surgical or radiation treatment.
- Patients with no prior chemotherapy for NSCLC including neoadjuvant or adjuvant treatment.
Who cannot join
- Patients are excluded if they have received any of the following within three weeks prior to first study treatment: investigational drugs, immunotherapy, gene therapy, hormone therapy (except leuprolide, and megestrol acetate for appetite stimulation), other biological therapy, chemotherapy or radiation. Patients with major surgery without full recovery or major surgery within 3 weeks prior to first study treatment are also excluded. Patients must have recovered from any previous major therapy-related toxicity (Grade 3 or 4) to < Grade 2 at study entry (except for neuropathy).
- Patients who have received radiation ≤ 3 weeks prior to study enrollment, whose marrow exposure has exceeded 30% or who have not recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia).
- Patients who have received prior high dose chemotherapy with hematopoietic stem cell rescue or stem cell or bone marrow transplant in the past two years.
- Patients with pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
- Patients with active symptomatic brain metastases. Patients with central nervous system (CNS) metastases are considered eligible if they have had adequately treated brain metastases, ie, have completed treatment (tapered off steroids) at least four weeks before starting treatment with E7389. Patients who have no evidence that the metastases are symptomatic or actively growing (no evidence of midline shift on computed tomography scan or magnetic resonance imaging) may be enrolled without initiation of local therapy for the CNS metastases. In this case, a repeat scan must be performed within four weeks of the original scan to ensure that disease progression is not occurring. It is not the intention of this study to treat patients with active brain metastases.
- Patients with meningeal carcinomatosis.
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- Patients who require therapeutic anti-coagulant therapy with warfarin or related compounds.
- Women who are pregnant or breast-feeding. Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the investigator (e.g., using 2 forms of contraception including a barrier method). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception.
- Patients with severe/uncontrolled intercurrent illness or infection.
- Patients with significant cardiovascular impairment (history of congestive heart failure > New York Heart Association Grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).
- Patients with organ allografts.
- Patients who have a history of positive testing for HIV and/or have active hepatitis B or active hepatitis C at study entry.
- Patients with pre-existing neuropathy > Grade 2.
- Patients with a hypersensitivity to halichondrin B and/or to a halichondrin B chemical derivative.
- Patients who participated in a prior E7389 clinical trial.
- Patients with other significant disease or disorders that, in the investigator's opinion, would exclude the patient from the study.
- For NSCLC patients at the MTD, the following additional exclusion criterion must be fulfilled:
- 1. Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated ≥ five years previously with no subsequent evidence of recurrence.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States4 sites
Study site
Lake Success, New York
Study site
New Brunswick, New Jersey
Study site
New York, New York
Study site
The Bronx, New York
India4 sites
Study site
Melur, Tamil Nadu
Study site
New Delhi, National Capital Territory of Delhi
Study site
Pune, Maharashtra
Study site
Vijayawada, Andhra Pradesh
About this study
Official title: A Phase Ib Open-Label, Two-Arm, Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors
The purpose of this study is to determine the maximum tolerated dose (MTD) and to explore the safety and anti-tumor activity of E7389 in combination with carboplatin in patients with advanced solid tumors.
Read the detailed description
This is a Phase Ib open-label, two-arm, dose-finding study of E7389 in combination with carboplatin in patients with solid tumors.
- Conditions
- Cancer
- Being tested
- E7389 + carboplatin AUC 5, E7389 + carboplatin AUC 6, E7389+carboplatin AUC 6
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E7389 + carboplatin AUC 5Drug
Patients will receive E7389 before (Schedule A) or after (Schedule B) carboplatin AUC 5 infusion. E7389 will be administered as a 2-5 minute intravenous (IV) bolus infusion at a starting dose of 0.7 mg/m^2 on Days 1 and 8 every 21 days. Carboplatin 5 AUC will be administered as a 30-minute IV infusion on Day 1 every 21 days. Dose escalation will be performed in cohorts of three patients per dose level per schedule.
E7389 + carboplatin AUC 6Drug
After MTD is reached with carboplatin AUC 5, dose escalation of E7389 in combination with carboplatin at AUC 6 will begin at one dose level below MTD, using the preferred schedule (A or B).
If carboplatin AUC 6 with E7389 is tolerated, the MTD reached will be used to enroll 20 additional patients with Stage IIIB or IV non-small cell lung cancer (NSCLC). If carboplatin AUC 6 is not tolerated, these patients will be enrolled at the MTD determined with the combination of E7389 and carboplatin AUC 5.
E7389+carboplatin AUC 6Drug
In a population of patients who had generally received multiple prior chemotherapies, the eribulin MTD has been determined to be 1.1 mg/m2 in combination with carboplatin at an AUC of 6. The first-line NSCLC patients in the extension arm may tolerate a higher dose of eribulin, because they have not been exposed to the toxicity of other chemotherapies. To investigate this possibility, the dose of eribulin will be increased to 1.4 mg/m2 for subsequent patients, if the first six of these patients do not experience a DLT during their first cycle of eribulin at 1.1 mg/m2 and carboplatin at AUC 6 combination therapy. If no more than one of the first six patients experience a DLT during the first cycle with the 1.4 mg/m2 dose of eribulin, then the 1.4 mg/m2 dose will be considered the recommended dose for front-line NSCLC therapy and the remaining patients will be treated using this dose.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: E7389 + carboplatin AUC 5 |
| 2 | Experimental | Not described Receives: Drug: E7389 + carboplatin AUC 6 |
| 3 | Experimental | Not described Receives: Drug: E7389+carboplatin AUC 6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Eribulin Mesylate of E7389 in Combination With Carboplatin in Subjects With Advanced Solid Tumors.
MTD was established by summarizing the number and percent of subject with dose- limiting toxicities (DLTs) for the first cycle.
Measured: 21 days (first cycle)
Secondary outcomes (2)
Safety of Eribulin Mesylate in Combination With Carboplatin as Measured by the Number of Subjects With Treatment Emergent Adverse Events.
Adverse events were considered treatment emergent if they started on or after the date of administration of the first dose of study drug, or if they were present prior to the administration of the first dose of study drug and increased in severity during the study.
Measured: Throughout the entire study
Percent of Subjects With Best Overall Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Objective response measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria and is Complete Response (disappearance of all target lesions) plus Partial Response (at least 30% decrease in sum of longest diameter [LD] of target lesions compared baseline sum of LD).
Measured: From start of eribulin treatment until disease progression or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2005 (estimated)
- Study startOct 2006
- Primary completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eisai US Medical Services, Study director, Eisai Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00268905
- Sponsor's protocol ID
- E7389-A001-104
- Status last verified
- Feb 2013
- First submitted
- 21 Dec 2005
- Last updated
- 12 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Goel S, Swami U, Kumar K, Dittrich C, Reyderman L, Jain M, Aisner J, Song J, Petrylak DP. A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer. Cancer Chemother Pharmacol. 2019 Sep;84(3):567-578. doi: 10.1007/s00280-019-03877-4. Epub 2019 Jun 12.
PubMed 31190276
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Open-Label, Two-Arm, Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT00268905
- Acronym / sponsor ID
- E7389-A001-104
- Conditions
- Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2006
- Primary completion
- Nov 2011 (actual)
- First posted
- 23 Dec 2005 (estimated)
- Results
- Posted 25 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the maximum tolerated dose (MTD) and to explore the safety and anti-tumor activity of E7389 in combination with carboplatin in patients with advanced solid tumors.
Detailed description
This is a Phase Ib open-label, two-arm, dose-finding study of E7389 in combination with carboplatin in patients with solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: E7389 + carboplatin AUC 5 |
| 2 | Experimental | Drug: E7389 + carboplatin AUC 6 |
| 3 | Experimental | Drug: E7389+carboplatin AUC 6 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients ≥ 18 years of age.
- Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Patients with a life expectancy of ≥ three months.
- Patients with adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula.
- Patients with adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, hemoglobin ≥ 10.0 g/dL (this may have been corrected by transfusion or growth factors) and platelet count ≥ 100 × 10^9/L.
Key exclusion criteria (19 listed)
- Patients are excluded if they have received any of the following within three weeks prior to first study treatment: investigational drugs, immunotherapy, gene therapy, hormone therapy (except leuprolide, and megestrol acetate for appetite stimulation), other biological therapy, chemotherapy or radiation. Patients with major surgery without full recovery or major surgery within 3 weeks prior to first study treatment are also excluded. Patients must have recovered from any previous major therapy-related toxicity (Grade 3 or 4) to < Grade 2 at study entry (except for neuropathy).
- Patients who have received radiation ≤ 3 weeks prior to study enrollment, whose marrow exposure has exceeded 30% or who have not recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia).
- Patients who have received prior high dose chemotherapy with hematopoietic stem cell rescue or stem cell or bone marrow transplant in the past two years.
- Patients with pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
- Patients with active symptomatic brain metastases. Patients with central nervous system (CNS) metastases are considered eligible if they have had adequately treated brain metastases, ie, have completed treatment (tapered off steroids) at least four weeks before starting treatment with E7389. Patients who have no evidence that the metastases are symptomatic or actively growing (no evidence of midline shift on computed tomography scan or magnetic resonance imaging) may be enrolled without initiation of local therapy for the CNS metastases. In this case, a repeat scan must be performed within four weeks of the original scan to ensure that disease progression is not occurring. It is not the intention of this study to treat patients with active brain 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 |
|---|---|---|
| E7389 + carboplatin AUC 5Patients will receive E7389 before (Schedule A) or after (Schedule B) carboplatin AUC 5 infusion. E7389 will be administered as a 2-5 minute intravenous (IV) bolus infusion at a starting dose of 0.7 mg/m^2 on Days 1 and 8 every 21 days. Carboplatin 5 AUC will be administered as a 30-minute IV infusion on Day 1 every 21 days. Dose escalation will be performed in cohorts of three patients per dose level per schedule. | Drug | 1 |
| E7389 + carboplatin AUC 6After MTD is reached with carboplatin AUC 5, dose escalation of E7389 in combination with carboplatin at AUC 6 will begin at one dose level below MTD, using the preferred schedule (A or B). If carboplatin AUC 6 with E7389 is tolerated, the MTD reached will be used to enroll 20 additional patients with Stage IIIB or IV non-small cell lung cancer (NSCLC). If carboplatin AUC 6 is not tolerated, these patients will be enrolled at the MTD determined with the combination of E7389 and carboplatin AUC 5. | Drug | 2 |
| E7389+carboplatin AUC 6In a population of patients who had generally received multiple prior chemotherapies, the eribulin MTD has been determined to be 1.1 mg/m2 in combination with carboplatin at an AUC of 6. The first-line NSCLC patients in the extension arm may tolerate a higher dose of eribulin, because they have not been exposed to the toxicity of other chemotherapies. To investigate this possibility, the dose of eribulin will be increased to 1.4 mg/m2 for subsequent patients, if the first six of these patients do not experience a DLT during their first cycle of eribulin at 1.1 mg/m2 and carboplatin at AUC 6 combination therapy. If no more than one of the first six patients experience a DLT during the first cycle with the 1.4 mg/m2 dose of eribulin, then the 1.4 mg/m2 dose will be considered the recommended dose for front-line NSCLC therapy and the remaining patients will be treated using this dose. | Drug | 3 |
Primary outcome
Maximum Tolerated Dose (MTD) of Eribulin Mesylate of E7389 in Combination With Carboplatin in Subjects With Advanced Solid Tumors.
Time frame: 21 days (first cycle)
MTD was established by summarizing the number and percent of subject with dose- limiting toxicities (DLTs) for the first cycle.
2 secondary outcomes
Safety of Eribulin Mesylate in Combination With Carboplatin as Measured by the Number of Subjects With Treatment Emergent Adverse Events.
Time frame: Throughout the entire study
Percent of Subjects With Best Overall Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Time frame: From start of eribulin treatment until disease progression or death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31190276Goel S, Swami U, Kumar K, Dittrich C, Reyderman L, Jain M, Aisner J, Song J, Petrylak DP. A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer. Cancer Chemother Pharmacol. 2019 Sep;84(3):567-578. doi: 10.1007/s00280-019-03877-4. Epub 2019 Jun 12.
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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.
Eisai US Medical Services study director
Eisai Inc.
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E7389 + carboplatin AUC 5, E7389 + carboplatin AUC 6 and E7389+carboplatin AUC 6 in people with Cancer, run by Eisai Inc. at 11 sites in 3 countries.
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 15 inclusion and 19 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 12 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, India, Austria. 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?
Yes. Results are posted in the registry (first posted 25 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of Eribulin Mesylate of E7389 in Combination With Carboplatin in Subjects With Advanced Solid Tumors. (time frame: 21 days (first cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00268905, which also lists 1 linked publication.
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 12 Feb 2013.