Kidney NeoplasmPhase 1NCT00005655
Combination Therapy of Interleukin-12 and Interleukin-2 to Treat Advanced Cancer
A Phase 1 study testing rh IL-12 and rh IL-2 in people with Kidney Neoplasm and Lung Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Kidney Neoplasm, Lung Neoplasm, Sarcoma
- What is being tested?
- rh IL-12 and rh IL-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Apr 2000to 2 Mar 2017
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients 18 years of age and older.
- Pathologically or cytologically-proven diagnosis of non-hematologic malignancy, and the presence of radiographically or clinically evaluable disease.
- Patients with solid tumors including renal, breast, lung carcinomas, as well as sarcomas for whom a proven more effective therapy does not exist. Patients with renal cell cancer will have received sunitinib or sorefinib or refused this option.
- Patients must not have received myelosuppressive chemotherapy, hormonal therapy, radiotherapy or immunotherapy within four weeks of entry onto this protocol.
- Estimated life expectancy of at least 12 weeks.
- ECOG performance status of 0 or 1.
Show all 18Show fewer
- Patients must be free of acute infection or other significant systemic illness.
- Negative serologic testing for hepatitis B will be required to limit confounding variables in the assessment of the potential hepatic toxicity of this combination.
- Negative serologic testing for human immunodeficiency virus (HIV) will be required given the uncertain impact of rhIL-12 and/or rhIL-2 administration on viral replication, and the potential alterations in immune responsiveness among patients concurrently infected with HIV.
- Adequate hepatic and renal function as evidence by:
- Transaminases less than 2.5 times the upper limit or normal;
- Total serum bilirubin less than 2.0 mg/dl;
- Serum Cr less than 2.0 mg/dl or calculated creatinine clearance of greater than 60 ml/min/1.73M(2).
- Adequate bone marrow function (without growth factor support) as evidence by:
- Absolute Neutrophil count (ANC) greater than 1500 cells/mm(3);
- Platelets greater than 100,000/mm(3).
- For women of childbearing potential, a negative urine pregnancy test within 14 days prior to initiation of study therapy is required. For patients of child-bearing potential, contraceptive precautions must be maintained during study participation.
- Normal pulmonary function (as documented by PFTs), and for patients over the age of 50, normal stress thallium testing. Normal pulmonary function testing will be defined as DLCO greater than 60% of predicted and FEVI greater than 70% of predicted.
Who cannot join
- Critically-ill or medically unstable patients.
- History or a presence of brain metastases.
- History of coronary artery disease, angina or myocardial infarction.
- Presence of clinically significant pleural effusion.
- History of malignant hyperthermia are.
- Concurrent or history of autoimmune disease.
Show all 16Show fewer
- History of congenital or acquired coagulation disorder.
- Patients with a history of ongoing or intermittent bowel obstruction.
- Women who are pregnant or lactating will be excluded.
- Systemic corticosteroids, radiotherapy, chemotherapy, or other investigational agents within 4 weeks prior to study entry.
- Patients who have received any of the following agents with known immunomodulatory effects within 4 weeks prior to study entry: G-CSF/GM-CSF, interferons or interleukins, growth hormone, IVIG, retinoic acid.
- Patients with a history of previous therapy with rhIL-12 will be excluded from study participation. For patients with renal cell carcinoma, a history of therapy with rhIL-2 will not exclude patients from study participation.
- Patients with concurrent administration of any other investigational agent.
- Patients with hematologic malignancies including leukemia or lymphoma.
- History of bone marrow or stem-cell transplantation.
- Intercurrent radiation therapy patients will be allowed on study if in the opinion of the principal investigator(s) its use is not necessitated by disease progression. For patients with disease progression, radiation therapy will be administered as clinically indicated and the patient will be withdrawn from study participation.
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 Investigation of IL-12/Pulse IL-2 in Adults With Advanced Solid Tumors
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.
Read more
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.
...
Read the 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 and/or refractory solid tumors.
To evaluate the pharmacokinetics of intravenous rhIL-12/pulse rhIL-2 administration in adults with various advanced and/or refractory solid tumors.
To provide a preliminary assessment of the ability of rhIL-12/pulse 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 and/or refractory solid tumors.
To evaluate the immunomodulatory activity of combined systemic administration of rhIL-12/pulse 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.
- Conditions
- Kidney Neoplasm, Lung Neoplasm, Sarcoma, Breast Neoplasm
- Being tested
- rh IL-12, rh IL-2
- Keywords
- Gene Expression, Neovascularization, antiangiogenic therapy, immunomodulatory therapy, Immunotherapy, Tumor
- Medical subject headings
- Kidney Neoplasms, Lung Neoplasms, Sarcoma, Breast Neoplasms, Neovascularization, Pathologic, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rh IL-12Biological
rhIL-12 will be administered intravenously on days 2, 4, 6, 10, 12 and 14 of each cycle.
rh IL-2Biological
rhIL-2 will be administered intravenously every 8 hours x 3 doses on days 1 and 9 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | rhIL-12 in combination with rhIL-2 Receives: Biological: rh IL-12; Biological: rh IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD and DLTof IL-12 in combination with IL-2
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2000 (estimated)
- Study start28 Apr 2000
- Primary completion6 Oct 2010
- Study completion2 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Kidney NeoplasmStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Thomas A Waldmann, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005655
- Sponsor's protocol ID
- 000121
- Other IDs
- 00-C-0121
- Status last verified
- 2 Mar 2017
- First submitted
- 4 May 2000
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007-8. doi: 10.1126/science.181845.
PubMed 181845Ruscetti FW, Morgan DA, Gallo RC. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol. 1977 Jul;119(1):131-8.
PubMed 141483Rubin JT. Interleukin-2: its biology and clinical application in patients with cancer. Cancer Invest. 1993;11(4):460-72. doi: 10.3109/07357909309018878. No abstract available.
PubMed 8324650
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 Investigation of IL-12/Pulse IL-2 in Adults With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00005655
- Acronym / sponsor ID
- 000121
- Conditions
- Kidney Neoplasm, Lung Neoplasm, Sarcoma, Breast Neoplasm
- Keywords
- Gene Expression, Neovascularization, antiangiogenic therapy, immunomodulatory therapy, Immunotherapy, Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 39 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 28 Apr 2000
- Primary completion
- 6 Oct 2010 (actual)
- Study completion
- 2 Mar 2017 (actual)
- First posted
- 5 May 2000 (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.
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.
...
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 and/or refractory solid tumors.
To evaluate the pharmacokinetics of intravenous rhIL-12/pulse rhIL-2 administration in adults with various advanced and/or refractory solid tumors.
To provide a preliminary assessment of the ability of rhIL-12/pulse 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 and/or refractory solid tumors.
To evaluate the immunomodulatory activity of combined systemic administration of rhIL-12/pulse 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: rh IL-12, Biological: rh IL-2rhIL-12 in combination with rhIL-2 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Adult patients 18 years of age and older.
- Pathologically or cytologically-proven diagnosis of non-hematologic malignancy, and the presence of radiographically or clinically evaluable disease.
- Patients with solid tumors including renal, breast, lung carcinomas, as well as sarcomas for whom a proven more effective therapy does not exist. Patients with renal cell cancer will have received sunitinib or sorefinib or refused this option.
- Patients must not have received myelosuppressive chemotherapy, hormonal therapy, radiotherapy or immunotherapy within four weeks of entry onto this protocol.
- Estimated life expectancy of at least 12 weeks.
Key exclusion criteria (16 listed)
- Critically-ill or medically unstable patients.
- History or a presence of brain metastases.
- History of coronary artery disease, angina or myocardial infarction.
- Presence of clinically significant pleural effusion.
- History of malignant hyperthermia are.
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 |
|---|---|---|
| rh IL-12rhIL-12 will be administered intravenously on days 2, 4, 6, 10, 12 and 14 of each cycle. | Biological | 1 |
| rh IL-2rhIL-2 will be administered intravenously every 8 hours x 3 doses on days 1 and 9 of each cycle. | Biological | 1 |
Primary outcome
MTD and DLTof IL-12 in combination with IL-2
Time frame: 1 month
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 181845Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007-8. doi: 10.1126/science.181845.
- Background: PubMed 141483Ruscetti FW, Morgan DA, Gallo RC. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol. 1977 Jul;119(1):131-8.
- Background: PubMed 8324650Rubin JT. Interleukin-2: its biology and clinical application in patients with cancer. Cancer Invest. 1993;11(4):460-72. doi: 10.3109/07357909309018878. No abstract available.
Related trials for Kidney Neoplasm
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
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.
Thomas A Waldmann, 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 rh IL-12 and rh IL-2 in people with Kidney Neoplasm and Lung Neoplasm, 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 18 inclusion and 16 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?
MTD and DLTof IL-12 in combination with IL-2 (time frame: 1 month). 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 NCT00005655, which also lists 3 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.