AMG 531 in Patients With Advanced Malignancy Receiving Treatment With Carboplatin
Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Solid Tumors; Advanced Cancer
Intervention: AMG 531 (Drug); Carboplatin (Drug); Adriamycin (Drug); Ifosfamide (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: M.D. Anderson Cancer Center Official(s) and/or principal investigator(s): Saroj Vadhan-Raj, MD, Principal Investigator, Affiliation: UT MD Anderson Cancer Center
Summary
The goal of this clinical research study is to find the highest safe dose of AMG 531 that
will decrease the risk and severity of thrombocytopenia (low platelet counts) in patients
who have received chemotherapy. Researchers will also look at the safety and effectiveness
of AMG 531 (Romiplostim).
Primary Objectives:
1. To determine the clinical safety and tolerability of AMG 531 administered following
chemotherapy in patients with advanced malignancy
2. To determine an optimal biologic dose (OBD) of AMG 531 administered in patients
receiving chemotherapy known to cause severe thrombocytopenia
3. To evaluate the effects of AMG 531 on the degree and duration of thrombocytopenia and
platelet recovery following chemotherapy
Secondary Objective:
1. To evaluate limited pharmacokinetics of AMG 531 administered by S. C. route
post-chemotherapy
Clinical Details
Official title: Phase I/II Study of AMG 531 in Patients With Advanced Malignancy Receiving Treatment With Carboplatin
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Number of Participants With Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following ChemotherapyNumber of Participants With Venous Thromboembolism (VTE) Related Serious Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy
Detailed description:
Platelets are cells that help make the blood clot. A decrease in platelets can cause
bleeding, which may prevent or delay a patient from receiving chemotherapy. Researchers want
to find out if AMG 531 can lower the risk and severity of this side effect. AMG 531 is a
protein that stimulates platelet production.
If you are eligible to take part in this study, you will be assigned to 1 of 6 dosing
schedules of study drug. The dose of AMG 531 that you receive will depend on when you are
enrolled.
In Cycle 1, all patients will receive chemotherapy by itself. Three (3) weeks later, in
Cycle 2, the same dose of chemotherapy will be given followed by AMG 531. AMG 531 will be
given on one of 3 schedules. AMG 531 will be given as an injection under the skin on the day
after chemotherapy and 2 days later; it will be given 5 days before and the day after
chemotherapy; or it will be given 5 and 3 days before chemotherapy and on the day after
chemotherapy and 2 days later. The schedule you receive will depend on when you enroll on
the study. After 2 cycles of treatment, based on response of the disease and tolerance to
the treatment, all participants may be able to receive up to 4 more cycles of chemotherapy
followed by AMG 531. All participants will continue on the same schedule you were receiving
before. The dose of AMG 531 may be increased at one time point during the study based on
the response of the platelet counts.
The number of blood tests drawn (about 3 teaspoons each) will depend on your clinical
condition. These samples will be taken at least 2 times a week and as often as once a day
during portions of the study. You will also have blood (about 1 teaspoon) collected for the
evaluation of anti-AMG 531 antibody status before treatment starts, at the end of Cycles 2
and 4, and at the end of study.
You will be taken off the study if your disease gets worse or intolerable side effects
occur. At the end of the study, you will have a medical history and physical exam, including
measurement of vital signs. You will also have blood (about 1 teaspoon) drawn for routine
tests.
This is an investigational study. AMG 531 is not FDA approved or commercially available.
At this time, it is being used for research purposes only. Up to 56 patients will take part
in this study. All will be enrolled at University of Texas (UT)MD Anderson.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Patients with a diagnosis of solid tumors who are at high risk for
chemotherapy-induced severe thrombocytopenia related to the following regimens: (a)
Carboplatin (AUC=11); (b) AI regimen (adriamycin 75-90mg/m2, Ifosfamide 10gm/m2); (c)
High dose Ifosfamide (14gm/m2)
2. Age >/= 18 years.
3. Adequate hematologic (Absolute neutrophil count (ANC) >/= 1500/mm^3, platelet count
>/= 100 x 10^9/L and Hgb >/= 8 gm/dL), renal (serum creatinine = 2. 0 mg/dL), and
hepatic functions (total bilirubin = 2 times, aspartate aminotransferase (AST or
SGOT) or alanine aminotransferase (ALT or SGPT) = 3 times the upper limit of the
respective normal range).
4. Karnofsky Performance Status >/= 80
5. Signed informed consent form
6. Patients with childbearing potential (defined as not post-menopausal for 12 months or
no previous surgical sterilization) must have a negative pregnancy test and use
adequate birth control. [i. e. oral contraceptives, spermicide with either a condom,
diaphragm or cervical cap, use of an intrauterine device (IUD), or abstinence].
Exclusion Criteria:
1. Patients with rapidly progressive disease (such as patients with rapidly accumulating
ascites or pleural effusion).
2. Patients with hematologic malignancies.
3. Pregnant or lactating women.
4. History of central nervous system (CNS) metastasis.
5. Patients with significant cardiac disease (New York Hearth Association (NYHA) Class
III or IV), dysrrhythmia, or recent history of MI or ischemia, transient ischemic
attack or cerebrovascular accident (CVA), within the previous 6 months of study
entry.
6. Patients with a history of thromboembolic events (history of deep venous thrombosis
(DVT) or pulmonary embolus).
7. Prior chemotherapy, immunotherapy, or experimental drug (not FDA-approved drug)
within 3 weeks. Patients will be eligible if day 1 of chemotherapy was initiated 3
weeks prior to study entry if the patient has recovery of blood counts and from acute
toxicity of chemotherapy as described in inclusion criteria # 3.
8. Use of nitrosourea (carmustine (BCNU), lomustine (CCNU) or mitomycin - C within 6
weeks of study entry.
9. Prior surgery or Radiation Therapy (RT) within 2 weeks of study entry.
10. Patients with history of prior whole pelvic radiation will be excluded unless there
is no prior history of severe thrombocytopenia (i. e. platelet nadir <10,000/mm^3)
11. Patients with history of prior high dose chemotherapy with stem cell transplant or
with history of prolonged thrombocytopenia (>/= 2 weeks).
12. History of any platelet disorders including Idiopathic thrombocytopenic purpura
(ITP), Thrombotic thrombocytopenic purpura (TTP) or bleeding disorders.
13. History of > 4 prior chemotherapy regimens (all platinum regimens will be counted as
one regimen).
14. Patients with significant bowel dysfunction secondary to tumor (significant abdominal
pain with severe constipation/diarrhea (>/= Grade 3), significant difficulty
maintaining oral nutrition).
15. Patients with pre-existing neuropathy > Grade 2.
Locations and Contacts
UT MD Anderson Cancer Center, Houston, Texas 77030, United States
Additional Information
UT MD Anderson Cancer Center
Starting date: August 2005
Last updated: April 7, 2014
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