Clinical trial NCT00147225
Conditions: Solid Tumors Advanced Cancer
Keywords: Advanced Cancer Advanced Malignancy Solid Tumors Thrombocytopenia AMG 531 Romiplostim Carboplatin Paraplatin Platelets Adriamycin Doxorubicin Rubex Ifosfamide Ifex
Sponsor: M.D. Anderson Cancer Center
Start date: 2005-08-01; Completion date: 2013-03-01
Enrollment: 55 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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

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.

Arms: arm 1: Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 1 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle.

Chemotherapy :

1. Carboplatin \[area under the concentration curve (AUC) = 11\]; or
2. Adriamycin - Ifosfamide (AI) regimen \[Adriamycin 75-90 mg/m\^2 intravenous (IV), Ifosfamide 10-14 gm/m\^2 IV\]; or
3. High dose Ifosfamide: 14 gm/m\^2. arm 2: Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 3 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle.

Chemotherapy :

1. Carboplatin \[area under the concentration curve (AUC) = 11\]; or
2. AI regimen \[Adriamycin 75-90 mg/m\^2 intravenous (IV), Ifosfamide 10-14 gm/m\^2 IV\]; or
3. High dose Ifosfamide: 14 gm/m\^2. arm 3: Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 10 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle.

Chemotherapy :

1. Carboplatin \[area under the concentration curve (AUC) = 11\]; or
2. AI regimen \[Adriamycin 75-90 mg/m\^2 intravenous (IV), Ifosfamide 10-14 gm/m\^2 IV\]; or
3. High dose Ifosfamide: 14 gm/m\^2. arm 4: Cycle 1, Chemotherapy (Control Cycle); Beginning Cycle 2, 10 mcg/kg AMG 531 subcutaneously on Day -5 (pre dose) and on day after chemotherapy (post dose) of 21-28 day treatment cycle.

Chemotherapy :

1. Carboplatin \[area under the concentration curve (AUC) = 11\]; or
2. AI regimen \[Adriamycin 75-90 mg/m\^2 intravenous (IV), Ifosfamide 10-14 gm/m\^2 IV\]; or
3. High dose Ifosfamide: 14 gm/m\^2. arm 5: Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 5 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) of 21-28 day treatment cycle.

Chemotherapy :

1. Carboplatin \[area under the concentration curve (AUC) = 11\]; or
2. AI regimen \[Adriamycin 75-90 mg/m\^2 intravenous (IV), Ifosfamide 10-14 gm/m\^2 IV\]; or
3. High dose Ifosfamide: 14 gm/m\^2. arm 6: 10 mcg/kg AMG 531 + Pre/Pre/Post/Post Chemotherapy Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 10 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) of 21-28 day treatment cycle.

Chemotherapy :

1. Carboplatin \[area under the concentration curve (AUC) = 11\]; or
2. AI regimen \[Adriamycin 75-90 mg/m\^2 intravenous (IV), Ifosfamide 10-14 gm/m\^2 IV\]; or
3. High dose Ifosfamide: 14 gm/m\^2.
Interventions: intervention 1: AMG 531 intervention 2: Carboplatin intervention 3: Adriamycin intervention 4: Ifosfamide
Intervention descriptions: intervention 1: Beginning with Cycle 2, administered in one of two schedules, either on day after chemotherapy and 2 days later (study cycle) or on day -5 (pre dose) and on day after chemotherapy (post dose) or combination of pre/post days of 21-28 day treatment cycle. Combination if Optimal biological dose (OBD) not reached, additional treatment at 10 mcg/kg dose level, with AMG 531 administered on day -5 (pre dose) and on day after chemotherapy (post dose).

1, 3, or 10 mcg/kg given as injection under the skin (subcutaneous) intervention 2: AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531. intervention 3: 75-90 mg/m\^2 IV intervention 4: 10 gm/m\^2 IV; OR, High dose ifosfamide = 14 gm/m\^2.

Protocol documents: