Colorectal Neoplasms Clinical Trial
Official title:
A Phase I/II Study of ISIS 183750 in Combination With Irinotecan in Irinotecan-refractory Colorectal Cancer
Background:
- Irinotecan is a drug that is used to treat colon or rectal cancer. It affects the DNA of
growing cancer cells. It is most often used with other chemotherapy drugs. Researchers want
to test it with an experimental drug, ISIS 183750. They want to see if the drugs are a safe
and effective treatment for advanced solid tumors or colorectal cancer that has not
responded to other treatments.
Objectives:
- To test the safety and effectiveness of ISIS 183750 with irinotecan for advanced solid
tumors or colorectal cancer.
Eligibility:
- Individuals at least 18 years of age who have solid tumors or colorectal cancer that has
not responded to other treatments.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine
samples will also be collected. Tumor tissue samples may be collected as well before
and after treatment. Imaging studies will also be performed.
- Participants will take ISIS 183750 once a week for 28-day cycles of treatment. On the
first cycle, they will also have ISIS 183750 on days 3 and 5.
- Participants will take irinotecan every second week, beginning on day 15 of the first
cycle.
- Treatment will be monitored with frequent blood tests and imaging studies.
- Treatment will continue as long as the cancer does not grow and the side effects are
not severe.
Status | Active, not recruiting |
Enrollment | 20 |
Est. completion date | December 2014 |
Est. primary completion date | December 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
- INCLUSION CRITERIA: - Phase I: Patients must have histopathological confirmation of carcinoma by the Laboratory of Pathology of the NCI prior to entering this study. - Phase II: Patients must have histopathological confirmation of Colorectal Carcinoma (CRC) by the Laboratory of Pathology of the NCI prior to entering this study. For this portion of the study patients must also have irinotecan-refractory colorectal cancer and have also received prior treatment for advanced/metastatic disease with an oxaliplatin-, bevacizumab-, or EGFR inhibitor-containing (only for subjects with wild type Kras) regimen. Irinotecan-refractory will be defined as patients who have radiological evidence of disease progression whilst receiving irinotecan or within 3 months after completing it. - Patients must have disease that is not amenable to potentially curative resection or ablative techniques and have received at least one prior standard chemotherapeutic regimen for metastatic disease. - All patients enrolled will be required to have measurable disease. For the phase II portion of the study patients must have disease that is amenable to biopsy and be willing to undergo this. - Age greater than18 years - Life expectancy of greater than 3 months - ECOG performance status 0-2 - Patients must have acceptable organ and marrow function as defined below: - leukocytes > 3,000/mcL - absolute neutrophil count > 1,500/mcL - platelets > 100,000/mcL - total bilirubin Within normal institutional limits - Serum albumin greater than or equal to 2.5 g/dL - Patients are eligible with ALT or AST measuring 3 x ULN if no liver metastasis or up to5 x ULN with liver metastasis. - creatinine < 1.5X institution upper limit of normal - OR - creatinine clearance > 45 mL/min/1.73 m2, as calculated below, for patients with creatinine levels above institutional normal - Estimated creatinine clearance (mL/min) - Females see calculations - Males see calculations - May use a 24 hr. urine collection to determine creatinine clearance. - Measured creatinine clearance (mL/min) - Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be < grade 1 or returned to baseline. - Patients must not have other invasive malignancies within the past 3 years (with the exception of non-melanoma skin cancers, carcinoma in situ of the cervix and noninvasive bladder cancer that has had successful curative treatment). - The effects of ISIS 183750 on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months after dosing with study medication ceases. However, adequate contraception for male patients should be used for 16 weeks post- last dose due to sperm life cycle. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of child-bearing potential must have a negative pregnancy test prior to entry. - Patient must be able to understand and willing to sign a written informed consent document. - Men and women of all races and ethnic groups are eligible for this trial. - Ejection fraction > 55% on echocardiogram. EXCLUSION CRITERIA: - Patients who have had chemotherapy (or so-called targeted systemic therapy), large field radiotherapy, or major surgery must wait 4 weeks after completing treatment prior to entering the study. - Patients may not be receiving any antineoplastics or other drugs intended to treat cancer within 4 weeks prior to starting ISIS 183750. - Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with clinically significant ascites, pleural effusion, and/or peripheral edema, unless the ascites or pleural effusion occurred as a result of malignancy. - Patients with known hypersensitivity to irinotecan. - Patients with known homozygous mutations in the UTG1A1 allele, or with unknown UTG1A1 status but who could not tolerate irinotecan even after dose reduction. - Patients with bleeding diathesis and subjects who are receiving anticoagulation treatment with INR > 2.5 are excluded. - Uncontrolled intercurrent illness including, but not limited to, hypertension (systolic BP > 160, diastolic BP > 100), ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements. - HIV-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and the investigational agent. - Known hepatitis B or hepatitis C infection. - Pregnancy and breast feeding are exclusion factors. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 3 months after the end of the treatment. |
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States,
André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V, de Gramont A. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 1999 Sep;35(9):1343-7. — View Citation
Bendell JC, Nemunaitis J, Vukelja SJ, Hagenstad C, Campos LT, Hermann RC, Sportelli P, Gardner L, Richards DA. Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2011 Nov 20;29(33):4394-400. doi: 10.1200/JCO.2011.36.1980. Epub 2011 Oct 3. — View Citation
Bennouna J, Lang I, Valladares-Ayerbes M, Boer K, Adenis A, Escudero P, Kim TY, Pover GM, Morris CD, Douillard JY. A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens. Invest New Drugs. 2011 Oct;29(5):1021-8. doi: 10.1007/s10637-010-9392-8. Epub 2010 Feb 2. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum tolerated dose | 2 years | Yes | |
Primary | Change of eIF4e and protein (HC) in pre- and post- tumor biopies | 2 years | No | |
Secondary | Evaluate the effect of eIF4E on relevant regulated proteins and immune cells | 2 years | No | |
Secondary | Evaluate Response Rate, PFS, and OS | 2 years | No | |
Secondary | Pharmacokinetic parameters | 2 years | No |
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