Ignite Creation Date:
2024-05-05 @ 10:18 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005655
Status:
TERMINATED
Last Update Posted:
2019-12-17
First Post:
2000-05-04
Brief Title:
Combination Therapy of Interleukin-12 and Interleukin-2 to Treat Advanced Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Investigation of IL-12Pulse IL-2 in Adults With Advanced Solid Tumors
Status:
TERMINATED
Status Verified Date:
2017-03-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purposes of this study are fourfold It will 1 determine what dose of interleukin-12 IL-12 and interleukin-2 IL-2 combination therapy can be given safely to patients with advanced cancer 2 evaluate the side effects of this treatment 3 examine how the body handles this drug combination and 4 determine whether and how the therapy may cause the immune system to stop or slow tumor growth
IL-2 is an approved drug for treating melanoma and kidney cancer IL-12 is an experimental drug that has shown anti-cancer activity in animals shrinking tumors and slowing their growth Animal studies suggest that given together the drugs may be more effective against cancer than either one singly
Patients 18 years of age and older with advanced solid-tumor cancers kidney breast lung sarcomas and others that do not improve with standard treatment may qualify for this study Candidates will have a physical examination including blood and urine tests electrocardiogram EKG and echocardiogram DTH skin test to test the function of the immune system chest X-ray and lung function tests to determine eligibility Bone marrow biopsy and imaging procedures such as CT and MRI scans may also be required Patients over 50 years old will also undergo exercise stress testing
Treatment will consist of four courses of IL-2 and IL-12 On days one and nine of each course patients will receive three doses one every 8 hours of IL-2 intravenously through a vein On days two four six 10 12 and 14 they will receive IL-12 intravenously This will be followed by a recovery period from days 15 through 35 This regimen will be repeated for another three cycles patients who show benefit without severe side effects may continue for additional cycles Treatment for the first cycle will be administered in the hospital If the drugs are well tolerated additional therapy may be given on an outpatient basis
A biopsy removal of a small sample of tumor tissue will be done at the beginning of the study after completing the first treatment cycle and possibly again when the cancer slows stops or gets worse or if the patient leaves the study These tumor samples will be examined to evaluate the effects of treatment Several blood samples also will be collected during the course of treatment to monitor immune system effects A device called a heparin lock may be put in place to avoid multiple needle sticks
IL-2 is an approved drug for treating melanoma and kidney cancer IL-12 is an experimental drug that has shown anti-cancer activity in animals shrinking tumors and slowing their growth Animal studies suggest that given together the drugs may be more effective against cancer than either one singly
Patients 18 years of age and older with advanced solid-tumor cancers kidney breast lung sarcomas and others that do not improve with standard treatment may qualify for this study Candidates will have a physical examination including blood and urine tests electrocardiogram EKG and echocardiogram DTH skin test to test the function of the immune system chest X-ray and lung function tests to determine eligibility Bone marrow biopsy and imaging procedures such as CT and MRI scans may also be required Patients over 50 years old will also undergo exercise stress testing
Treatment will consist of four courses of IL-2 and IL-12 On days one and nine of each course patients will receive three doses one every 8 hours of IL-2 intravenously through a vein On days two four six 10 12 and 14 they will receive IL-12 intravenously This will be followed by a recovery period from days 15 through 35 This regimen will be repeated for another three cycles patients who show benefit without severe side effects may continue for additional cycles Treatment for the first cycle will be administered in the hospital If the drugs are well tolerated additional therapy may be given on an outpatient basis
A biopsy removal of a small sample of tumor tissue will be done at the beginning of the study after completing the first treatment cycle and possibly again when the cancer slows stops or gets worse or if the patient leaves the study These tumor samples will be examined to evaluate the effects of treatment Several blood samples also will be collected during the course of treatment to monitor immune system effects A device called a heparin lock may be put in place to avoid multiple needle sticks
Detailed Description:
Background
Renal cell cancer responds to treatment with a variety of antiangiogenic and immunomodulatory drugs
In the RENCA model of renal cell cancer the combination of IL-12 and pulse IL-2 cures 88-100 of mice with established tumors
The tumor regression observed in this model is due to both antiangiogenic and immunologic effects
Objective
To define the maximum tolerated dose and dose-limiting toxicities of recombinant human IL-12 administered intravenously in combination with intermittent pulse recombinant human IL-2 in adults with various advanced andor refractory solid tumors
To evaluate the pharmacokinetics of intravenous rhIL-12pulse rhIL-2 administration in adults with various advanced andor refractory solid tumors
To provide a preliminary assessment of the ability of rhIL-12pulse rhIL-2 to modify neovascularization and gene expression in the local tumor site and to induce a measurable antitumor effect in adults with various advanced andor refractory solid tumors
To evaluate the immunomodulatory activity of combined systemic administration of rhIL-12pulse rhIL-2
Eligibility
Patients with advanced solid tumors for whom a proven more effective therapy does not exist Patients with renal cell cancer will be required to have received sunitinib or sorefinib or refused this option
The patient must have normal organ function and a life expectancy of at least 12 Weeks
Normal pulmonary function as documented by PFTs and for patients over the age of 50 normal stress thallium testing
No prior treatment with IL-12
Design
Phase I dose escalation with an expansion cohort of 10 patients treated at the maximum tolerated dose
Patients will be hospitalized for treatment IL-2 will be given intravenously every 8 hours on day 1 and this will be followed by intravenous administration of IL-12 every other day for three doses on days 2 4 and 6 After two days of rest the schedule will be repeated Cycles will be repeated every 36 days
Tumor response will be evaluated after every treatment Stable or responding patients will continue treatment with evaluations after every cycle of treatment
Renal cell cancer responds to treatment with a variety of antiangiogenic and immunomodulatory drugs
In the RENCA model of renal cell cancer the combination of IL-12 and pulse IL-2 cures 88-100 of mice with established tumors
The tumor regression observed in this model is due to both antiangiogenic and immunologic effects
Objective
To define the maximum tolerated dose and dose-limiting toxicities of recombinant human IL-12 administered intravenously in combination with intermittent pulse recombinant human IL-2 in adults with various advanced andor refractory solid tumors
To evaluate the pharmacokinetics of intravenous rhIL-12pulse rhIL-2 administration in adults with various advanced andor refractory solid tumors
To provide a preliminary assessment of the ability of rhIL-12pulse rhIL-2 to modify neovascularization and gene expression in the local tumor site and to induce a measurable antitumor effect in adults with various advanced andor refractory solid tumors
To evaluate the immunomodulatory activity of combined systemic administration of rhIL-12pulse rhIL-2
Eligibility
Patients with advanced solid tumors for whom a proven more effective therapy does not exist Patients with renal cell cancer will be required to have received sunitinib or sorefinib or refused this option
The patient must have normal organ function and a life expectancy of at least 12 Weeks
Normal pulmonary function as documented by PFTs and for patients over the age of 50 normal stress thallium testing
No prior treatment with IL-12
Design
Phase I dose escalation with an expansion cohort of 10 patients treated at the maximum tolerated dose
Patients will be hospitalized for treatment IL-2 will be given intravenously every 8 hours on day 1 and this will be followed by intravenous administration of IL-12 every other day for three doses on days 2 4 and 6 After two days of rest the schedule will be repeated Cycles will be repeated every 36 days
Tumor response will be evaluated after every treatment Stable or responding patients will continue treatment with evaluations after every cycle of treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-C-0121 | None | None | None |