A Phase 1/2 interventional study of E7050 and cisplatin in Advanced or Metastatic Solid Tumors and Previously Untreated Gastric Cancer, sponsored by Eisai Inc.. Terminated at 19 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-05-15.
Sponsored by Eisai Inc. · Phase 1/2, Interventional, and Treatment
The purpose of this study is to determine the following: 1. Find the maximum tolerated dose of E7050 when given in combination with cisplatin and capecitabine in patients with advance or metastatic solid tumors, and 2) Whether E7050 in combination with cisplatin and capecitabine is more effective in patients with previously untreated gastric cancer versus cisplatin and capecitabine alone.
This open-label, multicenter, randomized study will consist of 2 phases:
Phase Ib: a safety run-in period with 3 ascending doses of E7050 in combination with fixed doses of Cisplatin and Capecitabine. This phase will enroll approximately 10 to 15 patients.
In the phase II portion, Patients will receive study treatment , E7050 in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone) for approximately six 21-day cycles (18 weeks). Beyond 18 weeks, patients who are experiencing clinical benefit may continue E7050, with or without Capecitabine (Arm 1), or may continue Capecitabine alone (Arm 2), depending on the original randomization treatment arm. Patients will continue treatment for as long as clinical benefit is sustained and the treatment is well tolerated, until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or withdrawal by investigator, whichever occurs first. Patients will participate in either phase Ib or phase II.
2,851 studies on the registry are indexed under Stomach Neoplasms; 864 are open to participants now.
This study's enrollment of 7 is below the median of 67 across 2,096 interventional studies indexed under Stomach Neoplasms.
Browse Stomach Neoplasms studies →Eisai Inc. is the lead sponsor of 360 studies on the registry; 7 are open to participants now.
Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria
Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
Drug: E7050 · Drug: cisplatin · Drug: capecitabine
Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
Drug: E7050 · Drug: cisplatin · Drug: capecitabine
E7050 given orally at either 200, 300, or 400 mg once daily.
Cisplatin will be administered at 80 mg/m2 by intravenous infusion over 60 minutes on Day 1 of each 21-day treatment cycle.
Capecitabine will be administered at 1000 mg/m2 orally, twice daily (2000 mg/m2 total daily dose) on Days 1 through 14 of each 21-day treatment cycle.
Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib
On days when pharmacokinetic (PK) samples were to be drawn, a predose blood sample was obtained prior to administration of golvatinib and capecitabine. After administration of study drugs, a second postdose blood sample was taken. The amount of golvatinib in the participant's blood was analyzed and the AUC was calculated. The AUC reflects the actual body exposure to drug after administration of a dose of the drug and is dependent on the rate of elimination of the drug from the body and the dose administered. Predose samples that were below the limit of quantitation (BLQ) or missing were assigned a numerical value of zero for the calculation of AUC. Any other BLQ concentrations were assigned a value of zero. Results were expressed in nanograms·hour/milliter (ng·h/mL).
Time frame: Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.
Maximum Concentration (Cmax) of Golvatinib
Blood samples were drawn to analyze the amount of golvatinib in the participant's serum. Maximum concentration refers to the maximum (or peak) serum concentration of study drug in the participant's system after administration of the study drug and prior to the administration of a second dose of the study drug. Results were expressed in nanograms/milliliter (ng/mL).
Time frame: Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.
Number of Participants With a Treatment-Emergent Adverse Event (TEAE)
Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious AEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an adverse event (AE) that had an onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to 30 days after the date of last study treatment.
Time frame: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month.
Time to Maximum Concentration (Tmax) of Golvatinib
Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.
Time frame: Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.
Overall Response Rate (ORR)
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Time frame: Until disease progression or death for 3 years
Time to Progression (TTP)
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
Time frame: Until disease progression or death for 3 years
| Milestone | Phase 1b: Golvatinib+Capecitabine+Cisplatin | Phase 2: Golvatinib+Capecitabine+Cisplatin | Phase 2: Capecitabine + Cisplatin |
|---|---|---|---|
| Started | 7 | 0 | 0 |
| Completed | 1 | 0 | 0 |
| Not completed | 6 | 0 | 0 |
| Withdrew: Death | 4 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 2 | 0 | 0 |
| Milestone | Phase 1b: Golvatinib+Capecitabine+Cisplatin | Phase 2: Golvatinib+Capecitabine+Cisplatin | Phase 2: Capecitabine + Cisplatin |
|---|---|---|---|
| Started | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
On days when pharmacokinetic (PK) samples were to be drawn, a predose blood sample was obtained prior to administration of golvatinib and capecitabine. After administration of study drugs, a second postdose blood sample was taken. The amount of golvatinib in the participant's blood was analyzed and the AUC was calculated. The AUC reflects the actual body exposure to drug after administration of a dose of the drug and is dependent on the rate of elimination of the drug from the body and the dose administered. Predose samples that were below the limit of quantitation (BLQ) or missing were assigned a numerical value of zero for the calculation of AUC. Any other BLQ concentrations were assigned a value of zero. Results were expressed in nanograms·hour/milliter (ng·h/mL).
| ng·h/mL | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| Cycle 1, Day -2 | 23400 (5000 to 56100) |
| Cycle 2, Day 1 | 26300 (17400 to 62400) |
Blood samples were drawn to analyze the amount of golvatinib in the participant's serum. Maximum concentration refers to the maximum (or peak) serum concentration of study drug in the participant's system after administration of the study drug and prior to the administration of a second dose of the study drug. Results were expressed in nanograms/milliliter (ng/mL).
| ng/mL | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| Cycle 1, Day -2 | 1680 (268 to 3890) |
| Cycle 2, Day 1 | 1620 (834 to 3430) |
Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious AEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an adverse event (AE) that had an onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to 30 days after the date of last study treatment.
| Participants | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| Number of Participants With a Treatment-Emergent Adverse Event (TEAE) | 7 |
Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.
| Hours | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| Cycle 1, Day -2 | 3.00 (1.00 to 7.78) |
| Cycle 2, Day 1 | 6.07 (3.00 to 12.82) |
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
No measurements were reported for this outcome.
The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.
No measurements were reported for this outcome.
Collected over From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1b: Golvatinib+Capecitabine+Cisplatin | — | 5/7 (71.4%) | 7/7 (100%) |
| Event | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/7 |
| Psoas abscessInfections and infestations | 1/7 |
| PneumoniaInfections and infestations | 1/7 |
| Pulmonary embolismVascular disorders | 1/7 |
| ConvulsionNervous system disorders | 1/7 |
| NauseaGastrointestinal disorders | 1/7 |
| DehydrationMetabolism and nutrition disorders | 1/7 |
| Electrolyte imbalanceMetabolism and nutrition disorders | 1/7 |
| VomitingGastrointestinal disorders | 1/7 |
| Supraventricular tachycardiaCardiac disorders | 1/7 |
| Event | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| NauseaGastrointestinal disorders | 7/7 |
| DehydrationMetabolism and nutrition disorders | 5/7 |
| FatigueGeneral disorders | 5/7 |
| VomitingGastrointestinal disorders | 5/7 |
| Decreased appetiteMetabolism and nutrition disorders | 4/7 |
| Palmar-Plantar erythrodysaesthesia SyndromeSkin and subcutaneous tissue disorders | 4/7 |
| AnaemiaBlood and lymphatic system disorders | 3/7 |
| ConstipationGastrointestinal disorders | 3/7 |
| DiarrhoeaGastrointestinal disorders | 3/7 |
| HeadacheNervous system disorders | 3/7 |
| Age, Customized(Participants) | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| Age range 47 to 80 years | 7 |
| Sex: Female, Male(Participants) | Phase 1b: Golvatinib+Capecitabine+Cisplatin |
|---|---|
| Female | 4 |
| Male | 3 |
This study is terminated, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Eisai Inc.