Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00003970
Other study ID # NCI-2012-02304
Secondary ID 9531U01CA069852C
Status Completed
Phase Phase 1
First received November 1, 1999
Last updated January 23, 2013
Start date January 1999

Study information

Verified date January 2013
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical 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. 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


Description:

OBJECTIVES:

I. 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.


Recruitment information / eligibility

Status Completed
Enrollment 60
Est. completion date
Est. primary completion date October 2003
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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

- 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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms

  • AIDS-related Peripheral/Systemic Lymphoma
  • AIDS-related Primary CNS Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Burkitt Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hodgkin Disease
  • Intraocular Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, Mantle-Cell
  • Lymphoma, Non-Hodgkin
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Mycoses
  • Mycosis Fungoides
  • Nodal Marginal Zone B-cell Lymphoma
  • Primary Central Nervous System Non-Hodgkin Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Sezary Syndrome
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Stage III Adult Burkitt Lymphoma
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage III Adult Diffuse Mixed Cell Lymphoma
  • Stage III Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage III Adult Hodgkin Lymphoma
  • Stage III Adult Immunoblastic Large Cell Lymphoma
  • Stage III Adult Lymphoblastic Lymphoma
  • Stage III Adult T-cell Leukemia/Lymphoma
  • Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage III Grade 1 Follicular Lymphoma
  • Stage III Grade 2 Follicular Lymphoma
  • Stage III Grade 3 Follicular Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage III Marginal Zone Lymphoma
  • Stage III Mycosis Fungoides/Sezary Syndrome
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Adult Burkitt Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Mixed Cell Lymphoma
  • Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • Stage IV Adult Immunoblastic Large Cell Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Adult T-cell Leukemia/Lymphoma
  • Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Stage IV Marginal Zone Lymphoma
  • Stage IV Mycosis Fungoides/Sezary Syndrome
  • Stage IV Small Lymphocytic Lymphoma
  • Syndrome
  • Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
irinotecan hydrochloride
Given IV

Locations

Country Name City State
United States University of Chicago Comprehensive Cancer Center Chicago Illinois

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Up to 4 years Yes
Secondary Genotype A chi-squared test will be used to determine whether genotype and phenotype are independent. Up to 4 years No
Secondary 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. Up to 4 years No
See also
  Status Clinical Trial Phase
Completed NCT01828775 - Palliative Care Intervention in Improving Quality of Life, Psychological Distress, and Communication in Patients With Solid Tumors Receiving Treatment N/A
Terminated NCT01642342 - Recombinant Albumin Fusion Protein sEphB4-HSA in Treating Patients With Metastatic or Recurrent Solid Tumors Phase 1
Completed NCT00002950 - Topotecan Plus Sargramostim in Treating Patients With Advanced Cancer Phase 1/Phase 2
Completed NCT01705548 - Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis N/A
Completed NCT02146222 - VEGFR/PDGFR Dual Kinase Inhibitor X-82 and Docetaxel in Treating Patients With Solid Tumors Phase 1
Terminated NCT01602627 - Hsp90 Inhibitor AUY922 in Treating Older Patients With Advanced Solid Malignancies Phase 1
Completed NCT01191216 - 1-Methyl-D-Tryptophan and Docetaxel in Treating Patients With Metastatic Solid Tumors Phase 1
Recruiting NCT01137825 - Registry of Older Patients With Cancer
Recruiting NCT00992303 - Collecting Tissue Samples From Patients With Cancer Undergoing Radiation Therapy and Healthy Participants
Completed NCT00924651 - Exercise in Lessening Fatigue Caused by Cancer in Patients Undergoing Chemotherapy Phase 3
Completed NCT00949949 - Everolimus, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable Solid Tumors Refractory to Standard Therapy Phase 1
Suspended NCT00935090 - 3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer N/A
Withdrawn NCT00937417 - S0716 Vandetanib and Docetaxel in Treating Patients With Advanced Solid Tumors Phase 1
Active, not recruiting NCT00710632 - Screening to Predict Weight Loss in Patients With Cancer N/A
Completed NCT00573690 - Sorafenib Combined With Cisplatin and Etoposide or Carboplatin and Pemetrexed in Treating Patients With Metastatic Solid Tumors Phase 1
Completed NCT00544596 - R-(-)-Gossypol Acetic Acid, Cisplatin, and Etoposide in Treating Patients With Advanced Solid Tumors or Extensive Stage Small Cell Lung Cancer Phase 1
Active, not recruiting NCT00436735 - Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors Phase 1
Completed NCT00352443 - S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma Phase 1
Completed NCT00121277 - Vorinostat and Capecitabine in Treating Patients With Metastatic or Unresectable Solid Tumors Phase 1
Completed NCT00128622 - Denileukin Diftitox Followed by Vaccine Therapy in Treating Patients With Metastatic Cancer Phase 1