Phase 2
N=26
Safety and Efficacy Study for Solid Tumor Patients Treated With Eltrombopag
Thrombocytopaenia
Bottom Line
View on ClinicalTrials.gov: NCT01147809 ↗Enrolled (actual)
26
Serious AEs
38.6%
Results posted
Apr 2016
Primary outcome: Primary: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE): Pre-therapy, On-therapy + 30 Days and Post-therapy in Phase I — 3; 8; 4; 9 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Eltrombopag olamine (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jan 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE): Pre-therapy, On-therapy + 30 Days and Post-therapy in Phase I |
3; 8; 4; 9; 1; 0 | — |
| PRIMARY Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Hematology Parameters, at Anytime Post-Baseline in Phase I |
3; 9; 4; 10; 2; 1 | — |
| PRIMARY Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Clinical Chemistry Laboratory Parameters, at Anytime Post-Baseline in Phase I |
2; 4; 0; 4; 1; 2 | — |
| PRIMARY Number of Participants With a Change From Baseline in Creatinine of >=26.5 Micromoles/Liter (UMOL/L) in Phase I |
0; 3; 1; 2 | — |
| PRIMARY Number of the Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Scores at the Indicated Time Points in Phase I |
3; 5; 1; 3; 0; 3 | — |
| PRIMARY Number of Participants With Electrocardiogram (ECG) Findings at Anytime Post-Baseline in Phase I |
3; 8; 3; 7; 0; 1 | — |
| PRIMARY Mean Day 1 Scheduled Pre-chemotherapy Platelet Count Evaluated Across Cycles 1 to 6 in Phase II |
193.34; 246.20 | 0.103 |
| SECONDARY Average Pre-chemotherapy Platelet Count at the Indicated Time Points in Phase I |
239.3; 244.8; 223.8; 207.7; 180.7; 143.8 | — |
| SECONDARY Average Within-subject Central Laboratory Platelet Count Prior to Scheduled Chemotherapy Across Cycles 2 to 6 in Phase I |
296.80; 275.00; NA; NA; 235.00; 232.10 | — |
| SECONDARY Platelet Count Nadir for Each Chemotherapy Cycle in Phase I |
30.67; 106.56; 60.50; 99.00; 66.00; 122.44 | — |
| SECONDARY Central Laboratory Average Daily Area Under the Curve Platelet-time Course Across Cycles 2 to 6 in Phase I |
260.97; 307.59; 183.68; 291.18 | — |
| SECONDARY Number of Participants With Thrombocytopenia of Grade 1, 2, 3 or 4 Across All the Chemotherapy Cycles in Phase I, Using Central Laboratory Platelet Count |
0; 2; 1; 3; 0; 3 | — |
| SECONDARY Maximum Duration of Thrombocytopenia Across Cycles 2 to 6 in Phase I, Estimated Using Central Laboratory Platelet Counts |
11.0; 10.6; 14.7; 13.4 | — |
| SECONDARY Central Laboratory Platelet Count for Time Taken to Reach Platelet Nadir for Each Chemotherapy Cycle in Phase I |
15.7; 11.4; 13.8; 13.8; 15.0; 12.9 | — |
| SECONDARY Time to Recovery From Platelet Nadir for Each Chemotherapy Cycle in Phase I, Estimated Using Central Laboratory Platelet Counts |
5.3; 7.2; 7.0; 7.7; 6.5; 6.6 | — |
| SECONDARY Dose Intensity of Gemcitabine Plus Cisplatin (G+Cis)/Gemcitabine Plus Carboplatin (G+Cb) and Gemcitabine Across Chemotherapy Cycles 1 to 6 in Phase I |
100.0; 99.8; NA; NA; 100.0; 92.8 | — |
| SECONDARY Number of Participants With at Least One Delay in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase I |
1; 2; 2; 1 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE): Pre-therapy, On-therapy + 30 Days and Post-therapy in Phase II |
0; 1; 0; 0; 23; 48 | — |
| SECONDARY Number of Participants With Any Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale, Across Cycles 1-6 in Phase II |
11; 34; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants Requiring a Platelet Transfusion in Phase II |
0; 4; 2; 3; 0; 2 | — |
| SECONDARY Number of Participants With at Least One Delay in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase II |
5; 7; 4; 5; 1; 2 | — |
| SECONDARY Number of Participants With Any Dose Reduction in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase II |
7; 6; 2; 2; 0; 3 | — |
| SECONDARY Dose Intensity of Gemcitabine Plus Cisplatin(G+Cis)/Gemcitabine Plus Carboplatin (G+Cb) and Gemcitabine Across Chemotherapy Cycles 1-6 in Phase II |
96.6; 97.9; 113.1; 97.8; 102.6; 98.7 | — |
| SECONDARY Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Hematology Parameters, at Anytime Post-Baseline in Phase II |
23; 52; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Indicated Worst-case Change From Baseline in Clinical Chemistry Laboratory Parameters Using CTCAE Toxicity Grading, at Anytime Post-Baseline in Phase II |
10; 22; 0; 2; 0; 0 | — |
| SECONDARY Number of Participants With Change From Baseline in Creatinine of >=26.5 UMOL/L in Phase II |
5; 11 | — |
| SECONDARY Number of the Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Scores at the Indicated Time Points in Phase II |
3; 19; 19; 32; 1; 1 | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Findings at Cycle 1 Day 4 (2 to 6 Hours Post-dose) in Phase II |
0; 2; 20; 42; 2; 1 | — |
| SECONDARY Mean Day 8 Scheduled Pre-chemotherapy Platelet Counts Evaluated Across Cycles 1 to 6 in Phase II |
162.18; 180.65 | 0.407 |
| SECONDARY Mean Day 15 Scheduled Pre-chemotherapy Platelet Counts Evaluated Across Cycles 1 to 6 in Phase II |
95.10; 95.29 | 0.802 |
| SECONDARY Mean Within-subject Platelet Count Prior to Scheduled Chemotherapy Across Cycles 1 to 6 in Phase II |
221.0; 272.9; 201.0; 207.4; 97.5; 106.7 | — |
| SECONDARY Platelet Count Nadir for Each Chemotherapy Cycle in Phase II |
68.3; 77.2; 61.5; 68.5; 71.6; 84.7 | — |
| SECONDARY Average Daily Area Under the Platelet-time Course Across Cycles 1 to 6 in Phase II |
153.00; 189.48 | — |
| SECONDARY Number of Participants With Thrombocytopenia of Grade 1, 2, 3 or 4 Across Cycles 1 to 6 in Phase II |
4; 9; 3; 9; 8; 15 | — |
| SECONDARY Maximum Duration of Thrombocytopenia Across Cycles 1 to 6 in Phase II |
32.6; 23.5 | — |
| SECONDARY Time Taken to Reach Platelet Nadir for Each Chemotherapy Cycle in Phase II |
14.7; 15.7; 15.1; 15.4; 15.8; 14.3 | — |
| SECONDARY Time to Recovery From Platelet Nadir for Each Chemotherapy Cycle in Phase II |
8.1; 8.5; 9.3; 9.1; 9.9; 8.3 | — |
Summary
The present study is a randomized, blinded, placebo-controlled, two-Phase, sequential cohort, dose finding study to assess the safety and efficacy of eltrombopag in patients with solid tumors receiving gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin. Phase I of the study will examine safety and tolerability of various doses of eltrombopag to identify a dose and schedule of eltrombopag. Phase II will confirm that the chosen dose and schedule of eltrombopag from Phase I can deliver clinically meaningful benefit(s) to thrombocytopenic patients by improving platelet numbers.
Eligibility Criteria
Inclusion Criteria:Inclusion Criteria Subjects eligible for enrolment in Phase I and II of the study must meet all of the following criteria:
- Signed written informed consent.
- Age ≥ 18 years.
- Subjects with confirmed solid tumor and scheduled to receive at least two cycles of either gemcitabine monotherapy OR gemcitabine in combination with carboplatin or cisplatin at the same dosages and schedule in the study. Novel anticancer agents (e.g. bevacizumab, erlotinib) may be allowed if considered a standard treatment by the investigator. Subjects with only ONE current diagnosis of primary solid tumor will be allowed into the study.
- Note: For patients scheduled to receive any novel anticancer agents (e.g. bevacizumab, erlotinib), consultation and approval from the GSK medical monitor should occur before the subject is enrolled into the study.
- Life expectancy of at least 3 months, in the opinion of the investigator.
- ECOG-Zubrod performance status ≤ 2
- For Phase I: Pre-chemotherapy platelet count ≤ 300 Gi/L in the screening period before the subject start their first planned cycle of treatment with gemcitabine monotherapy OR gemcitabine in combination with carboplatin or cisplatin in the study.
- For Phase II (Part 1 and 2): Subjects must meet one of the following platelet count entry criteria:
- Subjects have not started the first cycle in this disease setting and have a platelet count 450 msec (QTc >480 msec for subjects with Bundle Branch Block) at study entry, or myocardial infarction within the preceding 6 months. Subjects with a34 pacemaker or defibrillator are not excluded provided that their cardiac function is within normal ranges.
- Note: For patients with pre-existing NYHA Grade II cardiovascular disease, the investigator should consult with GSK medical monitor before enrolling the subject into the study.
- Patients with known factor V leiden, antiphospholipid antibody syndrome, prothrombin gene mutations, ATIII deficiency, protein C deficiency, protein S deficiency OR recent history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism) within the preceding 6 months.
- Note: for patients with known risk factors for thromboembolism e.g., diabetes, hypercholesterolemia, recent major surgery etc., the investigator should consult with GSK medical monitor before enrolling the patient into the study and all risk factors should be documented in the CRF.
- Prior surgery within two weeks before study randomization or radiotherapy (RT) within four weeks before study randomization. Subjects with prior surgery or RT are not permitted into the study unless they have completely recovered from surgery and/or acute RT toxicity except for alopecia.
- Note: Note: patients with minor surgeries or outpatient procedures (e.g. insertion of central venous catheter) are immediately allowed in the study provided that there were no complications from the procedure or surgery.
- History of prior radiotherapy to more than 20% bone marrow bearing sites.
- History of platelet agglutination abnormality, platelet disorders or dysfunction or bleeding disorder that prevents reliable measurement of platelet counts.
- Subjects with a history of CNS metastases or clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan unless properly treated. Subjects with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to randomization will be excluded.
- Treated brain metastases are defined
- Having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed.
- Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination
Data sourced from ClinicalTrials.gov (NCT01147809). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.