Study of Drug to Reduce Thrombocytopenia in Patients Receiving Chemo for Ovarian, Fallopian Tube or Peritoneal Cancer

Study Overview
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Brief Summary
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This research study will investigate the safety and effectiveness of two different dose levels of a new, unapproved drug to be given along with the chemotherapy regimens gemcitabine and carboplatin or gemcitabine and cisplatin prescribed to women for the treatment of ovarian cancer. This experimental drug is called TXA127 and is being tested for effectiveness to see if it will help reduce some of the side effects of the chemotherapy, primarily low blood platelet levels that lead to excess bleeding. This study also intends to test the safety of TXA127 when given as an injection under the skin on a daily basis concurrently with up to 6 cycles of the prescribed chemotherapy.

Detailed Description
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This is a Phase IIb, multicenter, randomized, double-blind, placebo-controlled study comparing safety and efficacy of two dose levels of TXA127 when administered during 6 cycles of combination gemcitabine and platinum-based chemotherapy. This study intends to investigate the effectiveness of TXA127 for the mitigation of severity and/or incidence of thrombocytopenia, as well as safety when administered as a self-injected, subcutaneous solution. Females 18 years of age or older with a confirmed diagnosis of ovarian carcinoma who are scheduled to undergo combination chemotherapy with gemcitabine and carboplatin or gemcitabine and cisplatin will be considered for this study. Subjects may be chemotherapy naïve, newly diagnosed, or post a single course of chemotherapy followed by a progression- and treatment-free interval of at least 3 months, or post 2 or more previous courses of chemotherapy after a progression- and treatment-free interval of at least 6 months. Subjects will be randomized in a 1:1:1 ratio to one of the following three blinded treatment groups: placebo, 100 ug/kg/day TXA127 and 300 ug/kg/day TXA127. Treatment will be concurrent with up to six consecutive 21-day cycles of one of the following gemcitabine and platin regimens: Regimen A Intravenous cisplatin therapy at a dose of 30-50 mg/m2 given on Day 1 of the cycle Intravenous gemcitabine at a dose of 800 mg/m2 given on Day 1 after cisplatin and on Day 8 of the cycle. Regimen B Intravenous gemcitabine at a dose of 1000 mg/m2 given on Days 1 and 8 of the cycle Intravenous carboplatin AUC 4 given after gemcitabine on Day 1 of the cycle TXA127 will be self-administered as a subcutaneous injection by the subject once daily on Days 2-6 and 9-15 during each cycle of chemotherapy. Blood specimens will be drawn for hematologic analysis on Days 1, 8 and 15 of each treatment cycle.

Official Title
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Ph IIb Study Evaluating the Safety & Efficacy of TXA127 in the Reduction of Incidence and Severity of Thrombocytopenia in Patients Receiving Combination Gemcitabine and Platinum Therapy for Ovarian, Fallopian Tube, or Peritoneal Carcinoma

Conditions
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Thrombocytopenia, Neutropenia, Lymphopenia, Anemia

Intervention / Treatment
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* Drug: TXA127
* Drug: TXA127
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females at least 18 years of age with ovarian carcinoma who are one of the following: Newly diagnosed with ovarian cancer and chemotherapy naïve, or Post a single previous course of chemotherapy, with a 3-month disease-progression and treatment-free interval, with the exception of antibody therapy, prior to the study screening visit, or Post two or more previous courses of chemotherapy with a 6-month disease-progression and treatment-free interval, with the exception of antibody therapy, prior to the study screening visit. Must be scheduled for a course of combination chemotherapy consisting of gemcitabine and cisplatin or gemcitabine and carboplatin to be administered in 21-day cycles Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 Adequate bone marrow, renal, and hepatic functions as measured by standard chemistry and hematology blood tests Adequate blood coagulation parameters as measured by standard blood tests for coagulation Exclusion Criteria: Any clinical or laboratory abnormality greater than Grade 2 toxicity (NCI criteria), with the exception of laboratory parameters specified in the inclusion criteria Significant unstable cardiovascular disease Uncontrolled high blood pressure Current use of an angiotensin converting enzyme (ACE) inhibitor or angiotensin II antagonists Evidence of metastatic disease to the bone Metastatic disease to the CNS requiring treatment or radiation therapy Uncontrolled infection(s) Radiation therapy or chemotherapy (except as specified in the inclusion criteria) within the previous 5 years Concurrent use of hematopoietic or erythropoietic agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Combination gemcitabine and platinum-based chemotherapy with concurrent placebo | Drug: Placebo<br>* Once daily subcutaneous injection of placebo<br>|
| Experimental: TXA127 100 ug/kg<br>Combination gemcitabine and platinum-based chemotherapy with concurrent 100 ug/kg/day TXA127 | Drug: TXA127<br>* Once daily subcutaneous injection of 100 ug/kg<br>* Other names: Angiotensin 1-7;|
| Experimental: TXA127 300 ug/kg<br>Combination gemcitabine and platinum-based chemotherapy with concurrent 300 ug/kg/day TXA127 | Drug: TXA127<br>* Once daily subcutaneous injection of 300 ug/kg<br>* Other names: Angiotensin 1-7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy Cycles During Which the Platelet Count Measures Below 50,000/mm3 | Mean percentage of cycles with platelet counts below 50,000/mm3 | During a maximum of six 3-week chemotherapy cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Platelet Counts Below 50,000/mm3 | Number of subjects who experienced a platelet count below 50,000/mm3 | During a maximum of six 3-week chemotherapy cycles | 
| Treatment Cycles With Platelets Counts Below 25,000/mm3 | Mean percentage of treatment cycles where platelets counts were below 25,000/mm3 | During a maximum of six 3-week chemotherapy cycles | 
| Chemotherapy Dose Intensity and Dose Density | Mean percentage of cycles where projected (target) chemotherapy dose was maintained | During a maximum of six 3-week chemotherapy cycles | 
| Lymphopenia as Determined by Lymphocyte Count | Number of subjects with a treatment emergent adverse event of lymphopenia | During a maximum of six 3-week chemotherapy cycles | 
| Neutropenia | Number of subjects with a treatment emergent adverse event of neutropenia | During a maximum of six 3-week chemotherapy cycles | 
| Anemia | Number of subjects with a treatment emergent adverse event of anemia | During a maximum of six 3-week chemotherapy cycles | 
| Mucositis | Number of subjects with a treatment emergent adverse event of mucositis | During a maximum of six 3-week chemotherapy cycles | 
| Alopecia | Number of subjects with a treatment emergent adverse event of alopecia | During a maximum of six 3-week chemotherapy cycles | 
| Rescue Treatment for Hematopoiesis and Mucositis | Number of subjects with a treatment emergent adverse event of hematopoiesis and mucositis who received rescue treatment as determined by the administration of: Transfusions Filgrastim or Pegfilgrastim Erythropoietin Palifermin | During a maximum of six 3-week chemotherapy cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer, Thrombocytopenia, Cytopenia, Chemotherapy