LymphomaPhase 1NCT00562380
AMG-479 in Treating Patients With Advanced Solid Tumors or Non-Hodgkin Lymphoma
A Phase 1 study testing ganitumab, laboratory biomarker analysis and pharmacological study in people with Lymphoma and Prostate Cancer, run by Amgen at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Prostate Cancer, Sarcoma
- What is being tested?
- ganitumab, laboratory biomarker analysis and pharmacological study
- Type of treatment
- Surgery or procedure
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2005to Jun 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- ECOG performance status ≤ 2
- Not pregnant or nursing
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- 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
Who cannot join
- 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
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- 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:
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: A Phase 1, Open-Label, Dose Finding Study Evaluating the Safety and Pharmacokinetics of AMG 479 in Subjects With Advanced Solid Tumors
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.
Read the 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.
- Conditions
- Lymphoma, Prostate Cancer, Sarcoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- Being tested
- ganitumab, laboratory biomarker analysis, pharmacological study, biopsy
- 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
- Medical subject headings
- Lymphoma, Prostatic Neoplasms, Sarcoma, Immunoblastic Lymphadenopathy, Lymphoma, T-Cell, Cutaneous, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ganitumabBiological
laboratory biomarker analysisOther
biopsyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Pharmacokinetic profile
Secondary outcomes (7)
Level of insulin-like growth factor receptor-1 (IGF-1R) on peripheral blood cells
Tumor response measured by modified RECIST
Tumor glucose metabolism as measured by fludeoxyglucose F 18-PET/CT scan
Anti-AMG-479 antibody formation
The incidence of dose-limiting toxicities and the severity of adverse events
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2007 (estimated)
- Study startOct 2005
- Primary completionApr 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Mace L. Rothenberg, MD, FACP, Study chair, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00562380
- Sponsor's protocol ID
- AMGEN-479
- Other IDs
- CDR0000577404, AMGEN-20050118, VU-VICC-050630, VU-VICC-PHI-0542
- Status last verified
- Apr 2010
- First submitted
- 21 Nov 2007
- Last updated
- 18 Jul 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Dose Finding Study Evaluating the Safety and Pharmacokinetics of AMG 479 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00562380
- Acronym / sponsor ID
- AMGEN-479
- Conditions
- Lymphoma, Prostate Cancer, Sarcoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2005
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 22 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
- Willing to provide existing and/or future paraffin-embedded tumor samples
- ECOG performance status ≤ 2
- Not pregnant or nursing
Key exclusion criteria (55 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ganitumab | Biological | – |
| laboratory biomarker analysis | Other | – |
| pharmacological study | Other | – |
| biopsy | Procedure or surgery | – |
Primary outcome
Safety
Pharmacokinetic profile
7 secondary outcomes
Level of insulin-like growth factor receptor-1 (IGF-1R) on peripheral blood cells
Tumor response measured by modified RECIST
Tumor glucose metabolism as measured by fludeoxyglucose F 18-PET/CT scan
Anti-AMG-479 antibody formation
The incidence of dose-limiting toxicities and the severity of adverse events
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mace L. Rothenberg, MD, FACP study chair
Vanderbilt-Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ganitumab, laboratory biomarker analysis and pharmacological study in people with Lymphoma and Prostate Cancer, run by Amgen at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2013.