Advanced Adult Primary Liver CancerPhase 1NCT00004074
Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu
A Phase 1 study testing recombinant interleukin-12 and ABI-007/carboplatin/trastuzumab in people with Advanced Adult Primary Liver Cancer and Anaplastic Thyroid Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Adult Primary Liver Cancer, Anaplastic Thyroid Cancer, Bone Metastases
- What is being tested?
- recombinant interleukin-12 and ABI-007/carboplatin/trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1999to Feb 2009
- 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
- Patients must have a histologically proven Her2 overexpressing malignancy as determined by any standardized assay currently in clinical use
- Patients must have measurable or evaluable disease
- The patient must have failed standard curative and/or palliative therapies for their disease
- Life expectancy of at least 6 months
- No concurrent malignancy other than non-melanoma skin carcinoma
- Adequate hematopoietic, cardiac, renal, and hepatic function
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- Calculated creatinine clearance will be used to assess renal function
- Karnofsky Performance Status index >= 70%
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; a woman of childbearing potential is defined as a female who is biologically capable of becoming pregnant
- Normal cardiac ejection fraction by echocardiogram or MUGA (i.e., greater than OSU lower limit of normal)
- Written signed informed consent; the patient must be aware that his/her disease is neoplastic in nature and willingly consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
Who cannot join
- History of significant peripheral neuropathy or significant central nervous system disease
- Brain or central nervous system metastasis at entry
- Active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention; history of coronary artery disease or congestive heart failure
- Pregnant or nursing women
- Surgery, radiotherapy, chemotherapy, or hormonal therapy during the three weeks prior to the initiation of therapy
- Exposure to any investigational drug within three weeks prior to the start of dosing
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- Concurrent use of systemic corticosteroids
- Known seropositive for hepatitis B surface antigen
- Known seropositive for HIV antibody
- Serious concurrent infection requiring intravenous antibiotic therapy
- Clinically significant autoimmune disease (e.g., rheumatoid arthritis)
- Clinically significant gastrointestinal bleeding or uncontrolled peptic ulcer disease
- History of inflammatory bowel disease
- Any other major illness which, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study
- Prior therapy with Herceptin
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: A Phase I Trial of Herceptin and Interleukin-12
Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Phase I trial to study the effectiveness of interleukin-12 and trastuzumab in treating patients who have cancer that has high levels of HER2/neu and has not responded to previous therapy
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of interleukin-12 (IL-12) when combined with trastuzumab in patients with HER2-Neu overexpressing malignancies.
II. Determine the safety of this regimen in these patients.
III. Analyze any expression of interferon-inducible genes in tumor tissues of these patients after receiving this regimen.
IV. Characterize natural killer cytokine production in patients treated with this regimen.
- Determine serum interferon gamma levels in patients treated with this regimen.
OUTLINE:
This is a dose escalation study of interleukin-12 (IL-12).
Patients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks.
Cohorts of 3-6 patients receive escalating doses of IL-12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.
Patients are followed every 3 months for 1 year and then every 6 months thereafter for survival.
PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study within 6 months.
- Conditions
- Advanced Adult Primary Liver Cancer, Anaplastic Thyroid Cancer, Bone Metastases, Carcinoma of the Appendix, Distal Urethral Cancer, Fallopian Tube Cancer
- Being tested
- recombinant interleukin-12, ABI-007/carboplatin/trastuzumab
- Medical subject headings
- Thyroid Carcinoma, Anaplastic, Appendiceal Neoplasms, Fallopian Tube Neoplasms, Gastrinoma, Glucagonoma, Inflammatory Breast Neoplasms, Insulinoma, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant interleukin-12Biological
Also called cytotoxic lymphocyte maturation factor, IL-12, interleukin-12, natural killer cell stimulatory factor
Given IV
ABI-007/carboplatin/trastuzumabBiological
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (IL12 and trastuzumab) | Experimental | Patients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks. Receives: Biological: recombinant interleukin-12; Biological: ABI-007/carboplatin/trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 2.0 (CTCAE v2.0)
Measured: Up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2003 (estimated)
- Study startAug 1999
- Primary completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Adult Primary Liver CancerStudies 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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- William Carson, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004074
- Sponsor's protocol ID
- NCI-2012-01398
- Other IDs
- 99H0185, U01CA076576, CDR0000067282
- Status last verified
- Feb 2013
- First submitted
- 10 Dec 1999
- Last updated
- 28 Feb 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Herceptin and Interleukin-12
- ClinicalTrials.gov ID
- NCT00004074
- Acronym / sponsor ID
- NCI-2012-01398
- Conditions
- Advanced Adult Primary Liver Cancer, Anaplastic Thyroid Cancer, Bone Metastases, Carcinoma of the Appendix, Distal Urethral Cancer, Fallopian Tube Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 1999
- Primary completion
- Feb 2009 (actual)
- First posted
- 29 Oct 2003 (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.
Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Phase I trial to study the effectiveness of interleukin-12 and trastuzumab in treating patients who have cancer that has high levels of HER2/neu and has not responded to previous therapy
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of interleukin-12 (IL-12) when combined with trastuzumab in patients with HER2-Neu overexpressing malignancies.
II. Determine the safety of this regimen in these patients.
III. Analyze any expression of interferon-inducible genes in tumor tissues of these patients after receiving this regimen.
IV. Characterize natural killer cytokine production in patients treated with this regimen.
- Determine serum interferon gamma levels in patients treated with this regimen.
OUTLINE:
This is a dose escalation study of interleukin-12 (IL-12).
Patients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks.
Cohorts of 3-6 patients receive escalating doses of IL-12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.
Patients are followed every 3 months for 1 year and then every 6 months thereafter for survival.
PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study within 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (IL12 and trastuzumab) | Experimental | Biological: recombinant interleukin-12, Biological: ABI-007/carboplatin/trastuzumabPatients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have a histologically proven Her2 overexpressing malignancy as determined by any standardized assay currently in clinical use
- Patients must have measurable or evaluable disease
- The patient must have failed standard curative and/or palliative therapies for their disease
- Life expectancy of at least 6 months
- No concurrent malignancy other than non-melanoma skin carcinoma
Key exclusion criteria (15 listed)
- History of significant peripheral neuropathy or significant central nervous system disease
- Brain or central nervous system metastasis at entry
- Active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention; history of coronary artery disease or congestive heart failure
- Pregnant or nursing women
- Surgery, radiotherapy, chemotherapy, or hormonal therapy during the three weeks prior to the initiation of therapy
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 |
|---|---|---|
| recombinant interleukin-12Also: cytotoxic lymphocyte maturation factor, IL-12, interleukin-12, natural killer cell stimulatory factorGiven IV | Biological | Treatment (IL12 and trastuzumab) |
| ABI-007/carboplatin/trastuzumabGiven IV | Biological | Treatment (IL12 and trastuzumab) |
Primary outcome
Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 2.0 (CTCAE v2.0)
Time frame: Up to 52 weeks
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 28 Feb 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.
William Carson principal investigator
Ohio State University
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 recombinant interleukin-12 and ABI-007/carboplatin/trastuzumab in people with Advanced Adult Primary Liver Cancer and Anaplastic Thyroid Cancer, 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 11 inclusion and 15 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 28 Feb 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?
Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 2.0 (CTCAE v2.0) (time frame: Up to 52 weeks). 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 28 Feb 2013.