Ewing's SarcomaPhase 1NCT00428272
HGS-ETR2 to Treat Children With Solid Tumors
A Phase 1 study testing Lexatumumab alone, Lexatumumab in combination and Interferon gamma 1b in combination in people with Ewing's Sarcoma and Osteosarcoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background HGS-ETR2 is a monoclonal antibody, produced in the laboratory from human genes. HGS-ETR2 targets a protein called the TRAIL receptor that is located on the surface of some tumor cells. When the TRAIL receptor is activated, it can cause the tumor cell to self-destruct. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Ewing's Sarcoma, Osteosarcoma, Neuroblastoma
- What is being tested?
- Lexatumumab alone, Lexatumumab in combination and Interferon gamma 1b in combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Dec 2006to 9 Oct 2015
- 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 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- AGE: Patients must be greater than or equal to 1 years and less than or equal to 30 years of age in order to encompass a broad range of ages in children as well as to capture the young adult population which is highly represented in many of these types of sarcomas being studied.
- DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing s sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilm s tumor, Hodgkin's or non-Hodgkin's lymphoma. Patients with primary or untreated metastatic CNS tumors or primary or metastatic hepatic tumors will not be treated on this study.
- MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable tumors.
- PRIOR THERAPY:
- The patient s cancer must have relapsed following or failed to respond to standard therapy, and the patient s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- Patients must have completed their last dose of irradiation, chemotherapy, monoclonal antibody, or investigational therapy at least 4 weeks prior to enrollment or their last dose of nitrosurea (CCNU, BCNU) 6 weeks prior to enrollment. For patients who have undergone autologous stem cell transplantation, at least 3 months must have elapsed since transplant.
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- Patients must have recovered from the toxic effects of all prior therapy prior to enrollment.
- Patients must have been off colony stimulating factors (e.g. G-CSF, GM-CSF, Epo) for at least 72 hours prior to enrollment.
- Patients must have completed any biological therapy (including investigational therapies) at least 7 days prior to study entry.
- PERFORMANCE STATUS: Patients greater than 10 years old must have a Karnofsky Score of greater than or equal to 50 and children less than or equal to 10 years old must have a Lansky score of greater than 50. Patients who are unable to walk because of paralysis or weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
- HEMATOLOGIC FUNCTION: Patients must have adequate bone marrow function, defined as a peripheral absolute granulocyte count of greater than or equal to 1000/microliter, hemoglobin greater than or equal to 8 gm/dl, and a transfusion independent platelet count greater than or equal to 75,000/microliter.
- Cardiac Function: Patients must have an ejection fraction of greater than 40% via MUGA or Echo or a shortening fraction greater than 27% by Echo and must not have had a history of congestive heart failure.
- HEPATIC FUNCTION: Aspartate transaminase (AST) and alanine transaminase (ALT), less than or equal to 2.5-fold the upper limit of normal (ULN). Direct bilirubin within normal limits.
- RENAL FUNCTION: Patients must have normal age-adjusted serum creatinine (see Table below) OR a creatinine clearance greater than or equal to 60 mL/min/1.73 m(2).
- Age Less than or equal to 5 with a max serum creatinine (mg/dl) of 0.8
- Age less than 5 less than or equal to 10 with a max serum creatinine (mg/dl) of 1.0
- Age less than 10 less than or equal to 15 with a max serum creatinine (mg/dl) of 1.2
- Less than 15 with a max serum creatinine (mg/dl) of 1.5
- INFORMED CONSENT: All patients or their legal guardians (if the patients is less than18 years old) must sign a document of informed consent (Pediatric Oncology Branch, NCI screening protocol for NIH patients) prior to performing studies to determine patient eligibility. After confirmation of eligibility, all patients or their legal guardians must voluntarily sign the IRB approved protocol specific informed
- this study and their willingness to receive the therapy and to undergo the research studies involved including pharmacokinetic studies. The consent must be signed before any protocol related studies are performed (This does not include routine laboratory tests or imaging studies required to establish eligibility). When appropriate, pediatric patients will be included in all discussions in order to obtain verbal assent. Assent will be obtained according to local IRB requirements.
- DURABLE POWER OF ATTORNEY (DPA): Patients who are greater than or equal to 18 years of age will be offered the opportunity to assign a DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.
- BIRTH CONTROL: Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study and for 60 days following the last dose.
Who cannot join
- Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient s ability to tolerate the agents in this trial or are likely to interfere with the study procedures or results.
- Patients with a history of allogeneic bone marrow transplantation. Patients who have received autologous stem cell transplantation are eligible greater than 3 months after completion of therapy if they meet other eligibility requirements.
- Patients with hepatic tumors or metastases are excluded due to the potential for hepatotoxicity with agents that target the TRAIL-R pathway. Patients with primary CNS tumors will be excluded due to unknown penetration into the CNS.
- Untreated CNS metastases will render the patient ineligible however patients with a previous history of CNS metastases are eligible if: the metastases have been treated with surgery and/or radiotherapy, are clinically stable as evidenced by no requirements for corticosteroids, the patient has no evolving neurologic deficits and no change in residual brain abnormalities without specific therapy over 6 weeks.
- Pregnant or breastfeeding females are excluded because the risks of lexatumumab to the developing fetus or nursing child are unknown.
- Patients currently receiving other investigational agents.
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- History of any infection requiring hospitalization or parenteral antibiotics within 2 weeks of study entry.
- Co-existing medical illness that would place the subject at undue risk.
- On immunosupressant therapy (with the exception of prednisone up to 10 mg/day, or dexamethasone up to 4 mg/day), or with known human immunodeficiency virus (HIV) infection or hepatitis B or C. Subjects with immune deficiency are excluded due to their increased risk of life threatening toxicity when treated with anticancer agents.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) With or Without Interferon Gamma in Patients With Refractory Pediatric Solid Tumors
Background
- HGS-ETR2 is a monoclonal antibody, produced in the laboratory from human genes.
- HGS-ETR2 targets a protein called the TRAIL receptor that is located on the surface of some tumor cells. When the TRAIL receptor is activated, it can cause the tumor cell to self-destruct.
Read more
Objectives:
- To determine the highest dose of HGS-ETR2 that can be given safely in children and young adults with cancer.
- To study the pharmacology (how the body handles the drug) of HGS-ETR2 by measuring the amount of drug in the bloodstream over time before and after a dose is given to the patient.
- To determine if HGS-ETR2 can stop or slow tumor growth.
- To determine whether proteins in tumor tissue before treatment can predict whether the tumor will respond to HGS-ETR2 therapy.
Eligibility:
-Patients 1 to 21 years of age with solid cancers that do not respond to standard therapy.
Design:
- HGS-ETR2 is given through a vein (intravenously, IV) once every 14 days. Each treatment cycle is 28 days long and consists of two doses of HGS-ETR2.
- The dose of HGS-ETR2 is increased in successive small groups of patients until the maximum tolerated dose (highest dose with acceptable side effects) is determined.
- During the treatment period, patients have a physical examination at least once a week, and routine blood tests at least twice a week. These tests are done less frequently in later treatment cycles.
- Additional blood samples are drawn for immunology and pharmacology studies.
- Tests to monitor the size of the tumor (X-rays, CT scans, MRI, PET scans) are done periodically throughout the treatment period.
- Patients may continue to receive HGS-ETR2 until unacceptable side effects develop or the tumor grows.
Read the detailed description
Background:
Pediatric solid tumors represent approximately one fourth of cancer diagnoses in children. Despite intensive regimens, patients with metastatic or recurrent tumors have unsatisfactory survival rates. Therefore new therapies are needed to improve outcomes.
Members of the TNF ligand superfamily induce death in tumor cells through direct ligation of death receptors and apoptosis induction.
TRAIL (TNF-related apoptosis inducing ligand) has specific anti-tumor activity against a wide range of tumor cells without inducing death in normal cells. TRAIL-induced apoptosis has been demonstrated in a wide variety of pediatric solid tumors, including Ewing's sarcoma, osteosarcoma, neuroblastoma, and rhabdomyosarcoma.
HGS-ETR2 (Human Genome Sciences; human monoclonal antibody) is a fully human monoclonal antibody that agonistically binds TRAIL receptor 2 and, like TRAIL itself, induces apoptosis in a variety of malignant cell types with little effect on normal cells.
Limited caspase 8 expression is a primary factor in limiting to TRAIL mediated cell death in some tumors; interferon gamma has been shown to be effective in increasing caspase-8 expression in tumors and in restoring sensitivity of tumors to TRAIL mediated cell death.
Objectives:
To determine the tolerance of the adult maximum tolerated dose and dose limiting toxicities of lexatumumab in patients with refractory pediatric solid tumors.
To determine the MTD of lexatumumab in the presence of fixed dosing of interferon gamma 1b at 25 mcg/m(2) SC three times/week, which is less than the FDA approved dose.
To assess the pharmacokinetics of lexatumumab or lexatumumab in combination with interferon gamma 1b in patients with pediatric malignant tumors refractory to standard therapy.
Eligibility:
Patients must be 1-30 years of age with solid malignant tumors refractory to standard therapy.
Design:
A Phase I dose escalation study with 4 planned dose levels of lexatumumab starting at 30% of the adult MTD and escalating up to 100% of the adult MTD, followed by a second dose escalation using five lexatumumab dose levels in patients concomitantly receiving interferon gamma 1b.
Three (expanded to six if DLT occurs) patients will be enrolled at each dose level of lexatumumab until the adult MTD is reached and 6 patients will be enrolled at the adult MTD dose. The MTD cohort of lexatumumab alone and combined regimen will be expanded to include 12 patients, which should include a minimum of 6 patients less than or equal to 12 years of age. Once 6 patients greater than 12 years of age have completed lexatumumab alone, new patients greater than 12 years of age will be enrolled in the combined regimen. Similarly, once 6 patients complete lexatumumab alone who are less than or equal to 12 years of age, new patients less than or equal to 12 years of age will be enrolled in the combined regimen. A final dose escalation of interferon gamma 1b will be performed with the maximum dose level of lexatumumab, to a dose level wherein archival tissue demonstrated upregulation of caspase 8.
- Conditions
- Ewing's Sarcoma, Osteosarcoma, Neuroblastoma, Rhabdomyosarcoma
- Being tested
- Lexatumumab alone, Lexatumumab in combination, Interferon gamma 1b in combination, Gamma 1b potential expansion
- Keywords
- Monoclonal Antibody Lexatumumab, Interferon Gamma, Solid Tumor, Phase I, Malignant Tumor, Metastatic Tumor, Pediatric Solid Tumor, Ewing Sarcoma, Osteosarcoma, Neuroblastoma, Rhabdomyosarcoma
- Medical subject headings
- Sarcoma, Ewing, Osteosarcoma, Neuroblastoma, Rhabdomyosarcoma, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lexatumumab aloneDrug
Dose escalation : 3mg/kg, 5mg/kg, 8mg/kg, 10mg/kg
Lexatumumab in combinationDrug
Dose escalation : 1mg/kg, 3mg/kg, 5mg/kg, 8mg/kg, 10mg/kg
Interferon gamma 1b in combinationDrug
Dosing at the following for each lexatumumab dose level: .75mcg/m2/dose and 25mcg/m2/dose
Gamma 1b potential expansionDrug
Potential expansion (at 10mg/kg lexatumumab): 1.5mcg/m2/dose and 50mcg/m2/dose
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Lexatumumab alone dose escalation Receives: Drug: Lexatumumab alone |
| 2 | Experimental | Lexatumumab with interferon - dose escalation Receives: Drug: Lexatumumab in combination; Drug: Interferon gamma 1b in combination |
| 3 | Other | Lexatumumab 10mg/kg with interferon expansion at Receives: Drug: Lexatumumab in combination; Drug: Gamma 1b potential expansion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Asult MTD and DLTs of lexatumumab
Measured: 6 months
MTD of lexatumumab w/interferon gamma 1b
Measured: 6 months
Pharmacokinetics
Measured: 2 years
Secondary outcomes (3)
Tumor response rate
Measured: 2 years
Correlation of immunohistochemical expression of pro-apoptotic proteins with response to therapy
Measured: 2 years
Determine if anti-HGS-ETR2 antibodies are produced
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2007 (estimated)
- Study start4 Dec 2006
- Primary completion28 Apr 2011
- Study completion9 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ewing's SarcomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Crystal L Mackall, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00428272
- Sponsor's protocol ID
- 070040
- Other IDs
- 07-C-0040
- Status last verified
- 9 Oct 2015
- First submitted
- 25 Jan 2007
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995 Dec;3(6):673-82. doi: 10.1016/1074-7613(95)90057-8.
PubMed 8777713Georgakis GV, Li Y, Humphreys R, Andreeff M, O'Brien S, Younes M, Carbone A, Albert V, Younes A. Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicin- and bortezomib-induced cell death. Br J Haematol. 2005 Aug;130(4):501-10. doi: 10.1111/j.1365-2141.2005.05656.x.
PubMed 16098063Younes M, Georgakis GV, Rahmani M, Beer D, Younes A. Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma. Eur J Cancer. 2006 Mar;42(4):542-7. doi: 10.1016/j.ejca.2005.11.013. Epub 2006 Jan 19.
PubMed 16426839Merchant MS, Geller JI, Baird K, Chou AJ, Galli S, Charles A, Amaoko M, Rhee EH, Price A, Wexler LH, Meyers PA, Widemann BC, Tsokos M, Mackall CL. Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors. J Clin Oncol. 2012 Nov 20;30(33):4141-7. doi: 10.1200/JCO.2012.44.1055. Epub 2012 Oct 15.
PubMed 23071222
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) With or Without Interferon Gamma in Patients With Refractory Pediatric Solid Tumors
- ClinicalTrials.gov ID
- NCT00428272
- Acronym / sponsor ID
- 070040
- Conditions
- Ewing's Sarcoma, Osteosarcoma, Neuroblastoma, Rhabdomyosarcoma
- Keywords
- Monoclonal Antibody Lexatumumab, Interferon Gamma, Solid Tumor, Phase I, Malignant Tumor, Metastatic Tumor, Pediatric Solid Tumor, Ewing Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 4 Dec 2006
- Primary completion
- 28 Apr 2011 (actual)
- Study completion
- 9 Oct 2015 (actual)
- First posted
- 29 Jan 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.
Background
- HGS-ETR2 is a monoclonal antibody, produced in the laboratory from human genes.
- HGS-ETR2 targets a protein called the TRAIL receptor that is located on the surface of some tumor cells. When the TRAIL receptor is activated, it can cause the tumor cell to self-destruct.
Objectives:
- To determine the highest dose of HGS-ETR2 that can be given safely in children and young adults with cancer.
- To study the pharmacology (how the body handles the drug) of HGS-ETR2 by measuring the amount of drug in the bloodstream over time before and after a dose is given to the patient.
- To determine if HGS-ETR2 can stop or slow tumor growth.
- To determine whether proteins in tumor tissue before treatment can predict whether the tumor will respond to HGS-ETR2 therapy.
Eligibility:
-Patients 1 to 21 years of age with solid cancers that do not respond to standard therapy.
Design:
- HGS-ETR2 is given through a vein (intravenously, IV) once every 14 days. Each treatment cycle is 28 days long and consists of two doses of HGS-ETR2.
- The dose of HGS-ETR2 is increased in successive small groups of patients until the maximum tolerated dose (highest dose with acceptable side effects) is determined.
- During the treatment period, patients have a physical examination at least once a week, and routine blood tests at least twice a week. These tests are done less frequently in later treatment cycles.
- Additional blood samples are drawn for immunology and pharmacology studies.
- Tests to monitor the size of the tumor (X-rays, CT scans, MRI, PET scans) are done periodically throughout the treatment period.
- Patients may continue to receive HGS-ETR2 until unacceptable side effects develop or the tumor grows.
Detailed description
Background:
Pediatric solid tumors represent approximately one fourth of cancer diagnoses in children. Despite intensive regimens, patients with metastatic or recurrent tumors have unsatisfactory survival rates. Therefore new therapies are needed to improve outcomes.
Members of the TNF ligand superfamily induce death in tumor cells through direct ligation of death receptors and apoptosis induction.
TRAIL (TNF-related apoptosis inducing ligand) has specific anti-tumor activity against a wide range of tumor cells without inducing death in normal cells. TRAIL-induced apoptosis has been demonstrated in a wide variety of pediatric solid tumors, including Ewing's sarcoma, osteosarcoma, neuroblastoma, and rhabdomyosarcoma.
HGS-ETR2 (Human Genome Sciences; human monoclonal antibody) is a fully human monoclonal antibody that agonistically binds TRAIL receptor 2 and, like TRAIL itself, induces apoptosis in a variety of malignant cell types with little effect on normal cells.
Limited caspase 8 expression is a primary factor in limiting to TRAIL mediated cell death in some tumors; interferon gamma has been shown to be effective in increasing caspase-8 expression in tumors and in restoring sensitivity of tumors to TRAIL mediated cell death.
Objectives:
To determine the tolerance of the adult maximum tolerated dose and dose limiting toxicities of lexatumumab in patients with refractory pediatric solid tumors.
To determine the MTD of lexatumumab in the presence of fixed dosing of interferon gamma 1b at 25 mcg/m(2) SC three times/week, which is less than the FDA approved dose.
To assess the pharmacokinetics of lexatumumab or lexatumumab in combination with interferon gamma 1b in patients with pediatric malignant tumors refractory to standard therapy.
Eligibility:
Patients must be 1-30 years of age with solid malignant tumors refractory to standard therapy.
Design:
A Phase I dose escalation study with 4 planned dose levels of lexatumumab starting at 30% of the adult MTD and escalating up to 100% of the adult MTD, followed by a second dose escalation using five lexatumumab dose levels in patients concomitantly receiving interferon gamma 1b.
Three (expanded to six if DLT occurs) patients will be enrolled at each dose level of lexatumumab until the adult MTD is reached and 6 patients will be enrolled at the adult MTD dose. The MTD cohort of lexatumumab alone and combined regimen will be expanded to include 12 patients, which should include a minimum of 6 patients less than or equal to 12 years of age. Once 6 patients greater than 12 years of age have completed lexatumumab alone, new patients greater than 12 years of age will be enrolled in the combined regimen. Similarly, once 6 patients complete lexatumumab alone who are less than or equal to 12 years of age, new patients less than or equal to 12 years of age will be enrolled in the combined regimen. A final dose escalation of interferon gamma 1b will be performed with the maximum dose level of lexatumumab, to a dose level wherein archival tissue demonstrated upregulation of caspase 8.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Lexatumumab aloneLexatumumab alone dose escalation |
| 2 | Experimental | Drug: Lexatumumab in combination, Drug: Interferon gamma 1b in combinationLexatumumab with interferon - dose escalation |
| 3 | Other | Drug: Lexatumumab in combination, Drug: Gamma 1b potential expansionLexatumumab 10mg/kg with interferon expansion at |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- AGE: Patients must be greater than or equal to 1 years and less than or equal to 30 years of age in order to encompass a broad range of ages in children as well as to capture the young adult population which is highly represented in many of these types of sarcomas being studied.
- DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing s sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilm s tumor, Hodgkin's or non-Hodgkin's lymphoma. Patients with primary or untreated metastatic CNS tumors or primary or metastatic hepatic tumors will not be treated on this study.
- MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable tumors.
- The patient s cancer must have relapsed following or failed to respond to standard therapy, and the patient s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- Patients must have completed their last dose of irradiation, chemotherapy, monoclonal antibody, or investigational therapy at least 4 weeks prior to enrollment or their last dose of nitrosurea (CCNU, BCNU) 6 weeks prior to enrollment. For patients who have undergone autologous stem cell transplantation, at least 3 months must have elapsed since transplant.
Key exclusion criteria (9 listed)
- Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient s ability to tolerate the agents in this trial or are likely to interfere with the study procedures or results.
- Patients with a history of allogeneic bone marrow transplantation. Patients who have received autologous stem cell transplantation are eligible greater than 3 months after completion of therapy if they meet other eligibility requirements.
- Patients with hepatic tumors or metastases are excluded due to the potential for hepatotoxicity with agents that target the TRAIL-R pathway. Patients with primary CNS tumors will be excluded due to unknown penetration into the CNS.
- Untreated CNS metastases will render the patient ineligible however patients with a previous history of CNS metastases are eligible if: the metastases have been treated with surgery and/or radiotherapy, are clinically stable as evidenced by no requirements for corticosteroids, the patient has no evolving neurologic deficits and no change in residual brain abnormalities without specific therapy over 6 weeks.
- Pregnant or breastfeeding females are excluded because the risks of lexatumumab to the developing fetus or nursing child are unknown.
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 |
|---|---|---|
| Lexatumumab aloneDose escalation : 3mg/kg, 5mg/kg, 8mg/kg, 10mg/kg | Drug | 1 |
| Lexatumumab in combinationDose escalation : 1mg/kg, 3mg/kg, 5mg/kg, 8mg/kg, 10mg/kg | Drug | 2, 3 |
| Interferon gamma 1b in combinationDosing at the following for each lexatumumab dose level: .75mcg/m2/dose and 25mcg/m2/dose | Drug | 2 |
| Gamma 1b potential expansionPotential expansion (at 10mg/kg lexatumumab): 1.5mcg/m2/dose and 50mcg/m2/dose | Drug | 3 |
Primary outcome
Asult MTD and DLTs of lexatumumab
Time frame: 6 months
MTD of lexatumumab w/interferon gamma 1b
Time frame: 6 months
Pharmacokinetics
Time frame: 2 years
3 secondary outcomes
Tumor response rate
Time frame: 2 years
Correlation of immunohistochemical expression of pro-apoptotic proteins with response to therapy
Time frame: 2 years
Determine if anti-HGS-ETR2 antibodies are produced
Time frame: 2 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 8777713Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995 Dec;3(6):673-82. doi: 10.1016/1074-7613(95)90057-8.
- Background: PubMed 16098063Georgakis GV, Li Y, Humphreys R, Andreeff M, O'Brien S, Younes M, Carbone A, Albert V, Younes A. Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicin- and bortezomib-induced cell death. Br J Haematol. 2005 Aug;130(4):501-10. doi: 10.1111/j.1365-2141.2005.05656.x.
- Background: PubMed 16426839Younes M, Georgakis GV, Rahmani M, Beer D, Younes A. Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma. Eur J Cancer. 2006 Mar;42(4):542-7. doi: 10.1016/j.ejca.2005.11.013. Epub 2006 Jan 19.
- Derived from this study: PubMed 23071222Merchant MS, Geller JI, Baird K, Chou AJ, Galli S, Charles A, Amaoko M, Rhee EH, Price A, Wexler LH, Meyers PA, Widemann BC, Tsokos M, Mackall CL. Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors. J Clin Oncol. 2012 Nov 20;30(33):4141-7. doi: 10.1200/JCO.2012.44.1055. Epub 2012 Oct 15.
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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.
Crystal L Mackall, M.D. principal investigator
National Cancer Institute (NCI)
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 Lexatumumab alone, Lexatumumab in combination and Interferon gamma 1b in combination in people with Ewing's Sarcoma and Osteosarcoma, run by National Cancer Institute (NCI) 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 22 inclusion and 9 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: stopped early, as of the sponsor's last update on 17 Dec 2019. 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 was stopped early. Results are not available in the source record.
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?
Asult MTD and DLTs of lexatumumab (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00428272, which also lists 4 linked publications.
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 17 Dec 2019.