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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00771810

Enrollment

Registered

2008-10-13

Start date

2008-10-31

Completion date

2011-12-31

Last updated

2017-11-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anemia, Lymphopenia, Neutropenia, Thrombocytopenia

Keywords

Ovarian Cancer, Thrombocytopenia, Cytopenia, Chemotherapy

Brief summary

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

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.

Interventions

DRUGTXA127

Once daily subcutaneous injection of 100 ug/kg

DRUGPlacebo

Once daily subcutaneous injection of placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Treatment Cycles With Platelets Counts Below 25,000/mm3	During a maximum of six 3-week chemotherapy cycles	Mean percentage of treatment cycles where platelets counts were below 25,000/mm3
Chemotherapy Dose Intensity and Dose Density	During a maximum of six 3-week chemotherapy cycles	Mean percentage of cycles where projected (target) chemotherapy dose was maintained
Lymphopenia as Determined by Lymphocyte Count	During a maximum of six 3-week chemotherapy cycles	Number of subjects with a treatment emergent adverse event of lymphopenia
Neutropenia	During a maximum of six 3-week chemotherapy cycles	Number of subjects with a treatment emergent adverse event of neutropenia
Subjects With Platelet Counts Below 50,000/mm3	During a maximum of six 3-week chemotherapy cycles	Number of subjects who experienced a platelet count below 50,000/mm3
Mucositis	During a maximum of six 3-week chemotherapy cycles	Number of subjects with a treatment emergent adverse event of mucositis
Alopecia	During a maximum of six 3-week chemotherapy cycles	Number of subjects with a treatment emergent adverse event of alopecia
Rescue Treatment for Hematopoiesis and Mucositis	During a maximum of six 3-week chemotherapy cycles	Number of subjects with a treatment emergent adverse event of hematopoiesis and mucositis who received rescue treatment as determined by the administration of: 1. Transfusions 2. Filgrastim or Pegfilgrastim 3. Erythropoietin 4. Palifermin
Anemia	During a maximum of six 3-week chemotherapy cycles	Number of subjects with a treatment emergent adverse event of anemia

Countries

United States

Participant flow

Recruitment details

Subjects were recruited from Feb2009 to Feb2012 across 10 oncology sites.

Participants by arm

Arm	Count
Placebo Group 1: combination gemcitabine and platinum-based chemotherapy with concurrent placebo	10
TXA127 100 ug/kg Group 2: combination gemcitabine and platinum-based chemotherapy with concurrent 100 ug/kg/day TXA127	11
TXA127 300ug/kg Group 3: combination gemcitabine and platinum-based chemotherapy with concurrent 300 ug/kg/day TXA127	13
Total	34

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	3	0	2
Overall Study	Lost to Follow-up	0	0	1
Overall Study	Other	0	0	1
Overall Study	Physician Decision	1	2	2
Overall Study	Protocol Violation	0	1	1
Overall Study	Withdrawal by Subject	1	2	0

Baseline characteristics

Characteristic	Placebo	TXA127 100 ug/kg	TXA127 300ug/kg	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	2 Participants	3 Participants	7 Participants
Age, Categorical Between 18 and 65 years	8 Participants	9 Participants	10 Participants	27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants	11 Participants	13 Participants	34 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) Black or African American	0 Participants	2 Participants	0 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) White	8 Participants	9 Participants	11 Participants	28 Participants
Region of Enrollment United States	10 participants	11 participants	13 participants	34 participants
Sex: Female, Male Female	10 Participants	11 Participants	13 Participants	34 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	10 / 10	11 / 11	13 / 13
serious Total, serious adverse events	3 / 10	1 / 11	3 / 13