Lymphoma, Prostate Cancer, Sarcoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
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
Brief summary
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.
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.
Interventions
Sponsors
National Cancer Institute (NCI)
Amgen
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety | — |
| Pharmacokinetic profile | — |
Secondary
| Measure | Time frame |
|---|---|
| Tumor glucose metabolism as measured by fludeoxyglucose F 18-PET/CT scan | — |
| Anti-AMG-479 antibody formation | — |
| Level of insulin-like growth factor receptor-1 (IGF-1R) on peripheral blood cells | — |
| 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 | — |
| Circulating levels of IGF-1R and IGF-BP3 | — |
| The incidence of dose-limiting toxicities and the severity of adverse events | — |
| Tumor response measured by modified RECIST | — |
Countries
United States
Outcome results
None listed