Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors
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Purpose
RATIONALE: Nelfinavir may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of nelfinavir in treating patients with metastatic, refractory, or recurrent solid tumors.
| Condition | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer Gastrointestinal Carcinoid Tumor Head and Neck Cancer Islet Cell Tumor Lung Cancer Metastatic Cancer Neuroendocrine Carcinoma of the Skin Ovarian Cancer Pheochromocytoma Sarcoma Unspecified Adult Solid Tumor, Protocol Specific |
Drug: midazolam hydrochloride Drug: nelfinavir mesylate Genetic: gene expression analysis Genetic: polymerase chain reaction Genetic: protein expression analysis Other: immunoenzyme technique Other: immunologic technique Other: laboratory biomarker analysis Other: mass spectrometry |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors |
- Safety and toxicity [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Designated as safety issue: No ]
- Correlation of CYP3A4 activity with nelfinavir mesylate levels [ Designated as safety issue: No ]
- Clinical efficacy [ Designated as safety issue: No ]
- Biological and clinical effects of nelfinavir mesylate at the cellular and molecular level [ Designated as safety issue: No ]
| Estimated Enrollment: | 45 |
| Study Start Date: | September 2006 |
OBJECTIVES:
Primary
- Determine the safety and toxicity of nelfinavir mesylate in patients with metastatic, refractory, or recurrent solid tumors.
- Determine the maximum tolerated dose of this drug in these patients.
Secondary
- Determine the pharmacokinetics of this drug in these patients.
- Correlate cytochrome p450 3A4 (CYP3A4) activity with nelfinavir mesylate levels in these patients.
- Determine, preliminarily, the clinical efficacy of this drug in these patients.
- Assess the biological and clinical effects of this drug at the cellular and molecular level in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral nelfinavir mesylate twice daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may continue to receive nelfinavir mesylate.
Cohorts of 3-6 patients receive escalating doses of nelfinavir mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients receive oral midazolam hydrochloride on days -2 and 20 and then undergo blood collection on days -2 and 20 for midazolam pharmacokinetics to determine CYP3A4 activity. Nelfinavir mesylate pharmacokinetics are performed on day 1 of courses 1 and 2. Patients also undergo blood collection on days 1, 8, and 42 for biological marker laboratory studies, including vascular endothelial growth factor and basic fibroblast growth factor levels as measured by enzyme-linked immunosorbent assay and phospho-Akt, total Akt, cleaved Parp, Beclin 1, p-eIF2α, LC-3, and other signal transduction markers as measured by Western blot.
After completion of study treatment, patients are followed for 4 weeks.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed* solid malignancy for which there is no known curative therapy
- Relapsed disease OR failed to respond to standard therapy OR refused standard therapy in cases where no curative option exists NOTE: *An exception to histological confirmation will be allowed if no tissue is available for review, the presence of malignancy is documented in a pathology report from an outside institution, or a new biopsy is contraindicated because of safety.
Brain metastases allowed provided all of the following criteria are met:
- Prior evaluation and appropriate counseling
- Prior treatment by radiation oncology
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 3 months
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin < 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Creatinine < 1.5 times ULN
- Not nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
- No myocardial infarction within the past 6 months
No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 28 days since prior chemotherapy or biologic therapy
- No concurrent chemotherapy, biologic therapy, or radiotherapy
- No concurrent hormonal methods of birth control
No concurrent CYP3A4 inhibitors, including any of the following:
- Antiarrhythmics (e.g., amiodarone, quinidine)
- Neuroleptics (e.g., pimozide)
- Sedative or hypnotic agents (e.g., midazolam hydrochloride, triazolam)
- Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine)
Hydroxymethyl glutaryl co-enzyme A (HMG-CoA) reductase inhibitors (e.g., lovastatin, simvastatin, atorvastatin)
- Concurrent pravastatin and rovustatin allowed
- Rifampin
- Rifabutin
- Felodipine
- Nifedipine
- Sildenafil
- Hypericum perforatum (St. John's wort)
- No other concurrent anticancer agents or therapies
- No concurrent escalating doses of corticosteroids for other noncancerous medical conditions
Contacts and Locations| United States, Maryland | |
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | |
| Bethesda, Maryland, United States, 20892-1182 | |
| Principal Investigator: | Phillip Dennis, MD, PhD | National Cancer Institute (NCI) |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00436735 History of Changes |
| Other Study ID Numbers: | 070047, CDR0000529905, NCI-07-C-0047, NCI-P6880 |
| Study First Received: | February 15, 2007 |
| Last Updated: | September 29, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
unspecified adult solid tumor, protocol specific recurrent non-small cell lung cancer recurrent small cell lung cancer recurrent colon cancer recurrent rectal cancer recurrent adult soft tissue sarcoma recurrent uterine sarcoma ovarian sarcoma recurrent gastrointestinal carcinoid tumor pancreatic G-cell adenoma pancreatic G-cell carcinoma pancreatic alpha cell adenoma pancreatic alpha cell carcinoma pancreatic beta islet cell adenoma pancreatic beta islet cell carcinoma |
pancreatic delta cell adenoma pancreatic delta cell carcinoma recurrent islet cell carcinoma recurrent neuroendocrine carcinoma of the skin thyroid gland medullary carcinoma recurrent pheochromocytoma metastatic gastrointestinal carcinoid tumor regional gastrointestinal carcinoid tumor liver metastases lung metastases stage IV follicular thyroid cancer stage IV papillary thyroid cancer recurrent thyroid cancer stage IV neuroendocrine carcinoma of the skin |
Additional relevant MeSH terms:
|
Carcinoid Tumor Carcinoma Carcinoma, Merkel Cell Colorectal Neoplasms Head and Neck Neoplasms Lung Neoplasms Neoplasm Metastasis Neoplasms Neoplasms, Second Primary Ovarian Neoplasms Pheochromocytoma Carcinoma, Neuroendocrine Malignant Carcinoid Syndrome Gastrointestinal Neoplasms Adenoma, Islet Cell |
Skin Neoplasms Carcinoma, Basal Cell Carcinoma, Basosquamous Carcinoma, Squamous Cell Sarcoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Adenocarcinoma Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Intestinal Neoplasms Digestive System Neoplasms Neoplasms by Site |
ClinicalTrials.gov processed this record on May 16, 2013