AMG-479 in Treating Patients With Advanced Solid Tumors or Non-Hodgkin Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00562380
First received: November 21, 2007
Last updated: July 17, 2013
Last verified: April 2010
  Purpose

RATIONALE: Monoclonal antibodies, such as AMG-479, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

PURPOSE: This phase I trial is studying the side effects and best dose of AMG-479 in treating patients with advanced solid tumors or non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Prostate Cancer
Sarcoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Biological: ganitumab
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: biopsy
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose Finding Study Evaluating the Safety and Pharmacokinetics of AMG 479 in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Pharmacokinetic profile [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Level of insulin-like growth factor receptor-1 (IGF-1R) on peripheral blood cells [ Designated as safety issue: No ]
  • Tumor response measured by modified RECIST [ Designated as safety issue: No ]
  • Tumor glucose metabolism as measured by fludeoxyglucose F 18-PET/CT scan [ Designated as safety issue: No ]
  • Anti-AMG-479 antibody formation [ Designated as safety issue: No ]
  • The incidence of dose-limiting toxicities and the severity of adverse events [ Designated as safety issue: Yes ]
  • Levels of cross-linked c-telopeptides of type 1 collagen and bone-specific alkaline phosphatase (may also include tartrate-resistant acid phosphatase 5b) in blood [ Designated as safety issue: No ]
  • Circulating levels of IGF-1R and IGF-BP3 [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: October 2005
Study Completion Date: June 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To assess the safety and pharmacokinetics of anti-IGF-1R fully human monoclonal antibody AMG-479 (AMG-479) after multiple intravenous administrations in adult patients with histologically documented advanced solid tumors that are refractory to standard therapy or for which no curative therapy is available.

Secondary

  • To assess the tolerability and to determine the maximum tolerated dose of AMG-479.
  • To assess tumor glucose metabolism using PET/CT scanning with the tracer fludeoxyglucose F 18.
  • To measure insulin-like growth factor receptor (IGF-1R) levels on peripheral blood cells.
  • To establish whether human anti-human antibodies to AMG-479 develop in patients with advanced solid tumors.
  • To measure the tumor response by modified Response Evaluation Criteria in Solid Tumors.

Tertiary

  • To investigate bone turnover markers.
  • To investigate potential biomarker development by biochemical analysis in blood cells and tumor cells.

OUTLINE: This is a multicenter study.

  • Part 1 (dose-escalation): Patients receive escalating doses of anti-IGF-1R fully human monoclonal antibody AMG-479 (AMG-479) IV over 1 hour on days 1, 15, and 29. Patients are evaluated in week 8, and those who demonstrate an objective tumor response or stable disease continue treatment beginning on day 57. Treatment with AMG-479 repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
  • Part 2 (randomized dose-expansion): Patients are randomized to one of two dose regimens.

    • Arm I: Patients receive AMG-479 IV over 1 hour at a lower dose on day 1.
    • Arm II: Patients receive AMG-479 IV over 1 hour at a higher dose on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. Tumor tissue is obtained at baseline and after 4 weeks of study therapy for biomarker analysis.

Blood is drawn periodically for biomarker analysis (insulin-like growth factor [IGF]-1, IGF-binding protein 3 [IGF-BP3], IGF-1 receptor [IGF-1R], cross-linked c-telopeptides of type 1 collagen [CTx], bone-specific alkaline phosphatase [BSAP], and tartrate-resistant acid phosphatase [TRAP5b]) and pharmacokinetic studies.

After completion of study therapy, patients are followed for at least 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

  • Histologically or cytologically confirmed advanced solid tumors or non-Hodgkin lymphoma that is refractory to standard treatment or for which no curative therapy is available
  • Tumor tissue that is accessible for biopsy by using minimally invasive procedures and must consent to undergo biopsies of the tumor (part 2)

    • Exception for patients with Ewing family tumors or desmoplastic small round cell tumors whose anatomic location would pose an increase in the risk of injury due to biopsy (i.e., bleeding or pneumothorax)
  • Willing to provide existing and/or future paraffin-embedded tumor samples

Exclusion criteria:

  • Primary CNS tumors or hematological malignancies, other than non-Hodgkin lymphoma
  • Primary hepatic tumors or at increased risk for hepatic tumors, including any of the following:

    • Hepatitis of any etiology
    • Alcohol abuse or dependency
    • Hepatic adenoma
    • Follicular nodular hyperplasia
    • Autoimmune conditions associated with biliary tract cancer
    • Alpha 1 antitrypsin deficiency
    • Hemochromatosis
    • History of vinyl chloride or thorotrast/thorium dioxide exposure
  • History of histiocytic (Kupffer cell) neoplasia
  • Presence of untreated or symptomatic CNS metastases or symptoms of brain metastases
  • Presence of ascites or pleural effusion requiring medical intervention

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status ≤ 2
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Able to provide fasting blood samples for triglyceride and glucose laboratory tests
  • Able to fast for 4-6 hours for fludeoxyglucose F18-PET/CT scan
  • Controlled type 1 or 2 diabetes (defined as hemoglobin A1c < 8.0% and fasting blood glucose level < 160 mg/dL) allowed for part 2 only

Exclusion criteria:

  • History of clinically significant hypoglycemia or hyperglycemia (in the opinion of the investigator)
  • Myocardial infarction within the past year
  • Unstable or uncontrolled disease/condition related to or impacting cardiac function, including any of the following:

    • Unstable angina
    • Congestive heart failure
    • NYHA class III or IV heart disease
    • Uncontrolled hypertension (diastolic BP > 90 mm Hg and systolic BP > 150 mm Hg)
    • Clinically significant cardiac arrhythmia
    • CTCAE version 3.0 ≥ grade 2
    • Clinically significant electrocardiogram abnormalities
  • History of arterial or venous (deep vein) thrombosis within the past year
  • History of bleeding diathesis
  • History of chronic hepatitis
  • History of HIV infection
  • Unable to tolerate intravenous administration
  • Known sensitivity to mammalian-derived products
  • ANC < 1,500/mm^3 (without filgrastim [G-CSF] support within the past 2 weeks)
  • Platelet count < 100,000/mm^3 (without transfusion within the past 2 weeks)
  • Hemoglobin < 9 g/dL (without transfusion within the past 4 weeks)
  • PT/PTT > 1.5 x upper limit of normal (ULN)
  • Serum creatinine > 1.5 x ULN
  • AST and ALT > 2.5 x ULN
  • Total bilirubin > 1.5 x ULN
  • Urinary protein excretion > 1,000 mg/day (≥ 2+ using dipstick analysis)
  • Any kind of disorder that compromises the ability of the patient to give written informed consent and/or comply with study procedures
  • Any comorbid medical condition, that in the sponsor's or investigator's opinion, may put the patients at significant risk
  • Known sensitivity to any of the products to be administered during dosing
  • Unresolved toxicities > grade 1 from prior anticancer therapy, excluding alopecia

PRIOR CONCURRENT THERAPY:

  • No prior antitumor treatment within the past 28 days

    • Palliative external-beam radiotherapy to a lesion not used for RECIST measurement is acceptable during study for symptom management if patient is stable or improving and not progressing
  • At least 30 days since prior and no concurrent enrollment in another clinical trial involving medication
  • No antibody therapy for the treatment of underlying malignancy within the past 8 weeks
  • No concurrent or prior anticoagulation therapy, except low-dose warfarin (< 2 mg/day) for prophylaxis against central venous catheter thrombosis
  • No concurrent insulin (except diabetic patients enrolled in dose expansion [part 2] of the study)
  • No other concurrent investigational procedures
  • No concurrent blood or blood-product transfusions
  • No concurrent herbal medications
  • No other concurrent anticancer therapy including chemotherapy or hormonal therapy

    • Gonadotropic releasing-hormone agonists or antagonists allowed for advanced prostate cancer
  • No major surgery within the past month and none planned for 28 days after completion of study treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562380

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Amgen
Investigators
Study Chair: Mace L. Rothenberg, MD, FACP Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00562380     History of Changes
Other Study ID Numbers: AMGEN-479, CDR0000577404, AMGEN-20050118, VU-VICC-050630, VU-VICC-PHI-0542
Study First Received: November 21, 2007
Last Updated: July 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
cutaneous B-cell non-Hodgkin lymphoma
angioimmunoblastic T-cell lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
adult nasal type extranodal NK/T-cell lymphoma
anaplastic large cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
small intestine lymphoma
splenic marginal zone lymphoma
unspecified adult solid tumor, protocol specific
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
adult desmoplastic small round cell tumor
recurrent adult soft tissue sarcoma
recurrent prostate cancer

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Prostatic Neoplasms
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Neoplasms
Intestinal Neoplasms
Sarcoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Duodenal Diseases
Intestinal Diseases
Ileal Diseases
Jejunal Diseases
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on July 10, 2014