AIDS-related Peripheral/Systemic LymphomaPhase 1NCT00003970
Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma
A Phase 1 study testing irinotecan hydrochloride in people with AIDS-related Peripheral/Systemic Lymphoma and AIDS-related Primary CNS Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase I trial to study genetic testing and the effectiveness of irinotecan in treating patients who have solid tumors and lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Primary CNS Lymphoma, Anaplastic Large Cell Lymphoma
- What is being tested?
- irinotecan hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1999to Oct 2003
- 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 proven solid tumor or lymphoma
- Responded to irinotecan OR no existing curative therapy
- No leukemia
- Measurable or evaluable disease
- Performance status - Karnofsky 70-100%
- WBC at least 3500/mm^3
Show all 27Show fewer
- Absolute neutrophil count at least 1500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- SGOT/SGPT less than 5 times upper limit of normal (unless due to disease)
- Creatinine no greater than 1.5 mg/dL
- Creatinine clearance at least 60 mL/min
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No inflammatory bowel disease requiring therapy
- No chronic diarrhea syndrome or paralytic ileus
- At least 2 weeks since prior colony stimulating factor
- At least 4 weeks since prior biologic therapy
- No concurrent biologic therapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No other concurrent chemotherapy
- At least 4 weeks since prior radiotherapy to greater than 25% of bone marrow
- No concurrent palliative radiotherapy
- No prior transplant
- No concurrent substrates of UGT1A1 enzyme
- No concurrent inducers or inhibitors of UGT1A1 enzyme activity
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470
About this study
Official title: A Phase I Clinical Trial to Investigate the Correlation Between UGT1A1 Genotype and Irinotecan (CPT-11) Pharmacokinetics and Toxicity in Cancer Patients
Phase I trial to study genetic testing and the effectiveness of irinotecan in treating patients who have solid tumors and lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Genetic testing for a specific enzyme may help doctors determine whether side effects from or response to chemotherapy are related to a person's genetic makeup
Read the detailed description
OBJECTIVES:
- Classify patients with solid tumors or lymphoma according to UGT1A1 promoter (TATA box) and coding region (Gly71Arg) mutation, and CYP3A4 promoter (G to A) polymorphisms.
II. Identify UGT1A1 enzyme glucuronidator and irinotecan oxidizer phenotypes in these patients and determine the correlation between the two metabolic reactions in vivo.
III. Determine the relationship between UGT1A1 genotype (promoter and/or coding region mutation) and CYP3A4 promoter genotype vs gastrointestinal or bone marrow toxicity, and pharmacokinetics of irinotecan in these patients.
IV. Determine the pharmacokinetics of irinotecan in these patients.
OUTLINE: Patients are genotyped for UGT1A1 enzyme and classified as "Gilbert's" (7/7), "heterozygotes" (6/7), and "homozygotes for allele 6" (6/6). The DNA is analyzed for the UGT1A1 coding region mutation (Gly71Arg) and CYP3A4 promoter polymorphism. Patients are also examined for glucuronidator ratio of SN-38, the active metabolite of irinotecan, and classified as "low/slow" (very low or zero SN-38G/SN-38 ratio), "intermediate" (less than 50% normal ratio), or "normal".
Patients receive irinotecan IV over 90 minutes once every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity.
- Conditions
- AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Primary CNS Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma
- Being tested
- irinotecan hydrochloride
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Campto, Camptosar, CPT-11, irinotecan
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (irinotecan hydrochloride) | Experimental | Patients receive irinotecan IV over 90 minutes once every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: irinotecan hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade 3-4 diarrhea
A Cochran-Armitage test for trend will be used to determine whether there is a linear trend in the proportion of patients within each genotype experiencing grade 3-4 diarrhea. Similarly, trend analysis will be performed to determine if there is a linear trend in the proportion of patients within each phenotype experiencing grade 3-4 myelosuppression. Genotype (3 ordered levels) will be modeled as a function of metabolic ratios and biliary index to determine whether these are independent.
Measured: Up to 4 years
Secondary outcomes (2)
Genotype
A chi-squared test will be used to determine whether genotype and phenotype are independent.
Measured: Up to 4 years
Phenotype
A chi-squared test will be used to determine whether genotype and phenotype are independent. Modeled as a function of metabolic ratios and biliary index.
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startJan 1999
- Primary completionOct 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AIDS-related Peripheral/Systemic LymphomaStudies 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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Ratain, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003970
- Sponsor's protocol ID
- NCI-2012-02304
- Other IDs
- 9531, U01CA069852, CDR0000067173
- Status last verified
- Jan 2013
- First submitted
- 1 Nov 1999
- Last updated
- 24 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial to Investigate the Correlation Between UGT1A1 Genotype and Irinotecan (CPT-11) Pharmacokinetics and Toxicity in Cancer Patients
- ClinicalTrials.gov ID
- NCT00003970
- Acronym / sponsor ID
- NCI-2012-02304
- Conditions
- AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Primary CNS Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 1999
- Primary completion
- Oct 2003 (actual)
- First posted
- 27 Jan 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.
Phase I trial to study genetic testing and the effectiveness of irinotecan in treating patients who have solid tumors and lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Genetic testing for a specific enzyme may help doctors determine whether side effects from or response to chemotherapy are related to a person's genetic makeup
Detailed description
OBJECTIVES:
- Classify patients with solid tumors or lymphoma according to UGT1A1 promoter (TATA box) and coding region (Gly71Arg) mutation, and CYP3A4 promoter (G to A) polymorphisms.
II. Identify UGT1A1 enzyme glucuronidator and irinotecan oxidizer phenotypes in these patients and determine the correlation between the two metabolic reactions in vivo.
III. Determine the relationship between UGT1A1 genotype (promoter and/or coding region mutation) and CYP3A4 promoter genotype vs gastrointestinal or bone marrow toxicity, and pharmacokinetics of irinotecan in these patients.
IV. Determine the pharmacokinetics of irinotecan in these patients.
OUTLINE: Patients are genotyped for UGT1A1 enzyme and classified as "Gilbert's" (7/7), "heterozygotes" (6/7), and "homozygotes for allele 6" (6/6). The DNA is analyzed for the UGT1A1 coding region mutation (Gly71Arg) and CYP3A4 promoter polymorphism. Patients are also examined for glucuronidator ratio of SN-38, the active metabolite of irinotecan, and classified as "low/slow" (very low or zero SN-38G/SN-38 ratio), "intermediate" (less than 50% normal ratio), or "normal".
Patients receive irinotecan IV over 90 minutes once every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (irinotecan hydrochloride) | Experimental | Drug: irinotecan hydrochloridePatients receive irinotecan IV over 90 minutes once every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Histologically proven solid tumor or lymphoma
- No leukemia
- Measurable or evaluable disease
- Performance status - Karnofsky 70-100%
- WBC at least 3500/mm^3
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| irinotecan hydrochlorideAlso: Campto, Camptosar, CPT-11, irinotecanGiven IV | Drug | Treatment (irinotecan hydrochloride) |
Primary outcome
Grade 3-4 diarrhea
Time frame: Up to 4 years
A Cochran-Armitage test for trend will be used to determine whether there is a linear trend in the proportion of patients within each genotype experiencing grade 3-4 diarrhea. Similarly, trend analysis will be performed to determine if there is a linear trend in the proportion of patients within each phenotype experiencing grade 3-4 myelosuppression. Genotype (3 ordered levels) will be modeled as a function of metabolic ratios and biliary index to determine whether these are independent.
2 secondary outcomes
Genotype
Time frame: Up to 4 years
Phenotype
Time frame: Up to 4 years
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 24 Jan 2013.
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.
Mark Ratain principal investigator
University of Chicago Comprehensive 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 irinotecan hydrochloride in people with AIDS-related Peripheral/Systemic Lymphoma and AIDS-related Primary CNS Lymphoma, 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 27 inclusion and 0 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 24 Jan 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?
Grade 3-4 diarrhea (time frame: Up to 4 years). 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 24 Jan 2013.