AMG 531 in Patients With Advanced Malignancy Receiving Treatment With Carboplatin

NCT00147225 | Completed Phase 1 Results

• 1 other identifier: 2005-0099
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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. 1.To determine the clinical safety and tolerability of AMG 531 administered following chemotherapy in patients with advanced malignancy
2. 2.To determine an optimal biologic dose (OBD) of AMG 531 administered in patients receiving chemotherapy known to cause severe thrombocytopenia
3. 3.To evaluate the effects of AMG 531 on the degree and duration of thrombocytopenia and platelet recovery following chemotherapy

Conditions

Solid Tumors; Advanced Cancer

Keywords

Advanced Cancer; Advanced Malignancy; Solid Tumors; Thrombocytopenia; AMG 531; Romiplostim; Carboplatin; Paraplatin; Platelets; Adriamycin; Doxorubicin; Rubex; Ifosfamide; Ifex

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy

  Number of participants experiencing an adverse event (AE) or serious adverse event (SAE) during study treatment, possible or probable related to study drug. All toxicities graded using the Common Terminology Criteria for Adverse Events version 3.0. Participation has a maximum of 6 cycles of chemotherapy on the study.

  Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles

• Number of Participants With Venous Thromboembolism (VTE) Related Serious Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy

  Number of participants experiencing an venous thromboembolism (VTE) related serious adverse event (SAE) during study treatment, possible or probable related to study drug. All toxicities graded using the Common Terminology Criteria for Adverse Events version 3.0. Participation has a maximum of 6 cycles of chemotherapy on the study. VTE events reported are part or whole total number reported for study SAEs, not in addition to SAEs reported.

  Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles

Study Arms (6)

1 mcg/kg AMG 531 Post Chemotherapy

EXPERIMENTAL

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.

Drug: AMG 531; Drug: Carboplatin; Drug: Adriamycin; Drug: Ifosfamide

3 mcg/kg AMG 531 Post Chemotherapy

EXPERIMENTAL

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.

Drug: AMG 531; Drug: Carboplatin; Drug: Adriamycin; Drug: Ifosfamide

10 mcg/kg AMG 531 Post Chemotherapy

EXPERIMENTAL

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.

Drug: AMG 531; Drug: Carboplatin; Drug: Adriamycin; Drug: Ifosfamide

10 mcg/kg Pre/Post Chemotherapy

EXPERIMENTAL

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.

Drug: AMG 531; Drug: Carboplatin; Drug: Adriamycin; Drug: Ifosfamide

5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy

EXPERIMENTAL

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.

Drug: AMG 531; Drug: Carboplatin; Drug: Adriamycin; Drug: Ifosfamide

10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy

EXPERIMENTAL

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.

Drug: AMG 531; Drug: Carboplatin; Drug: Adriamycin; Drug: Ifosfamide

Interventions

AMG 531 DRUG

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)

Also known as: Romiplostim

1 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy; 10 mcg/kg Pre/Post Chemotherapy; 3 mcg/kg AMG 531 Post Chemotherapy; 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy

Carboplatin DRUG

AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531.

Also known as: Paraplatin

1 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy; 10 mcg/kg Pre/Post Chemotherapy; 3 mcg/kg AMG 531 Post Chemotherapy; 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy

Adriamycin DRUG

75-90 mg/m\^2 IV

Also known as: Doxorubicin, Rubex

1 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy; 10 mcg/kg Pre/Post Chemotherapy; 3 mcg/kg AMG 531 Post Chemotherapy; 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy

Ifosfamide DRUG

10 gm/m\^2 IV; OR, High dose ifosfamide = 14 gm/m\^2.

Also known as: Ifex

1 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Post Chemotherapy; 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy; 10 mcg/kg Pre/Post Chemotherapy; 3 mcg/kg AMG 531 Post Chemotherapy; 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Age \>/= 18 years.
• 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).
• Karnofsky Performance Status \>/= 80
• Signed informed consent form
• 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. \[i.e. oral contraceptives, spermicide with either a condom, diaphragm or cervical cap, use of an intrauterine device (IUD), or abstinence\].

You may not qualify if:

• Patients with rapidly progressive disease (such as patients with rapidly accumulating ascites or pleural effusion).
• Patients with hematologic malignancies.
• Pregnant or lactating women.
• History of central nervous system (CNS) metastasis.
• 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.
• Patients with a history of thromboembolic events (history of deep venous thrombosis (DVT) or pulmonary embolus).
• Use of nitrosourea (carmustine (BCNU), lomustine (CCNU) or mitomycin - C within 6 weeks of study entry.
• Prior surgery or Radiation Therapy (RT) within 2 weeks of study entry.
• 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)
• Patients with history of prior high dose chemotherapy with stem cell transplant or with history of prolonged thrombocytopenia (\>/= 2 weeks).
• History of any platelet disorders including Idiopathic thrombocytopenic purpura (ITP), Thrombotic thrombocytopenic purpura (TTP) or bleeding disorders.
• History of \> 4 prior chemotherapy regimens (all platinum regimens will be counted as one regimen).
• Patients with significant bowel dysfunction secondary to tumor (significant abdominal pain with severe constipation/diarrhea (\>/= Grade 3), significant difficulty maintaining oral nutrition).
• Patients with pre-existing neuropathy \> Grade 2.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Amgen: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Thrombocytopenia

Interventions

romiplostim; Carboplatin; Doxorubicin; Ifosfamide

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Saroj Vadhan-Raj
• Organization: University of Texas MD Anderson Cancer Center

svadhanr@mdanderson.org

713-792-7966

Study Officials

• Saroj Vadhan-Raj, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 7, 2005
• Study Start: August 1, 2005
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: May 8, 2014
• Results First Posted: May 8, 2014

Record last verified: 2014-04

Locations

US (1)