Vinorelbine and XR9576 to Treat Cancer

NCT00001944 | Completed Phase 1

• 2 other identifiers: 00004400-C-0044
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Tumor resistance to anti-cancer drugs is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps chemotherapy drugs out of the cells, reducing treatment effectiveness. In laboratory tests, an experimental drug called XR9576, has blocked pumping by this protein. It is being used in this study to try to increase the amount of the anti-cancer drug vinorelbine, in cancer cells. Vinorelbine has been shown in several clinical trials to be effective against some advanced cancers, including breast, lung and ovarian, and is one of the drugs pumped out of tumor cells by P-glycoprotein. Patients with cancer 18 years and older may be eligible for this study. Candidates will be screened with tests that may include blood and urine tests, electrocardiogram, echocardiogram, CT scans, X-rays, and nuclear medicine studies. A tumor biopsy may be done for diagnostic or research purposes. Study participants will undergo tumor imaging with the radioactive drug Tc-99m Sestamibi. This drug accumulates in tumor cells and is eliminated from them in much the same way that some cancer drugs are eliminated from cells. The drug is injected into a vein and a series of pictures are taken with a gamma camera. After this baseline scan, patients will receive a dose of XR9576 and undergo a second scan 24 hours later. The scan will show whether XR9576 affects the accumulation and elimination of Sestamibi in tumor cells. This procedure may provide a way to monitor cancers for evidence of chemotherapy resistance and show if XR9576 can improve the effectiveness of therapy. At least 10 days after the baseline and XR9576 scans, patients will begin the first of 3 or more 21-day cycles of vinorelbine treatment. On days 1 and 8 of each cycle, patients will receive a 30-minute infusion of XR9576 intravenously (through a vein) followed by vinorelbine, infused over a 6- to 10-minute period. (In some patients, XR9576 will be administered before only one of the two vinorelbine dosages.) Physical examination, blood tests, and other procedures may be done periodically to monitor treatment.

Conditions

Breast Cancer; Cancer; Lung Cancer; Ovarian Cancer

Keywords

Drug Resistance; MDR-1; P-Glycoprotein Blocker; Pgp; Resistance Reversal

Interventions

Vinorelbine DRUG

XR9576 DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Age greater than or equal to 18 years. Histologic or cytologic confirmation of cancer, for which there is no known standard therapy capable of extending life expectancy. Performance status ECOG 0-2. Life expectancy of 3 months or greater. Platelet count greater than or equal to 90,000/mL. Absolute granulocyte count (AGC) greater than or equal to 1,000/mL. Serum creatinine less than or equal to 1.5 mg/dl (or if greater than 1.5, measured creatinine clearance greater than or equal to 50 mL/min). SGPT and SGOT less than or equal to 2.5 times normal limit, and bilirubin less than or equal to 1.5 times normal limit (in patients with clinical evidence of Gilbert's disease, less than or equal to 3 times normal limit). 2 weeks from prior radiation or chemotherapy and recovery from associated toxicities such that they meet eligibility criteria. Hormonal therapy may be taken up to the time of enrollment. No serious intercurrent medical illness. Bidimensionally measurable disease by radiographic means or physical examination; or relevant tumor markers (i.e. CA-125 and PSA greater than or equal to 2 times upper limit of normal). The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol. No pregnant or nursing women; or women of childbearing potential unless using effective contraception as determined by the patient's physician. No history of another malignancy; specifically, no patients with a non-skin malignancy or with melanoma within the past 5 years; no concomitant malignancy that has not been curatively treated. However, cancer survivors who have undergone potentially curative therapy for a prior malignancy at least 5 years before enrollment is considered, and are deemed at low risk for recurrence by their treating physicians. No patients with current or a history of CNS metastases. No patients who are a poor medical risk because of other non malignant systemic disease or active, uncontrolled infection. No HIV seropositive patients. No prior vinorelbine therapy.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ling V, Thompson LH. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol. 1974 Feb;83(1):103-16. doi: 10.1002/jcp.1040830114. No abstract available.

  PMID: 4855907 BACKGROUND

• Beck WT, Cirtain MC, Lefko JL. Energy-dependent reduced drug binding as a mechanism of Vinca alkaloid resistance in human leukemic lymphoblasts. Mol Pharmacol. 1983 Nov;24(3):485-92.

  PMID: 6579344 BACKGROUND

• Fairchild CR, Ivy SP, Kao-Shan CS, Whang-Peng J, Rosen N, Israel MA, Melera PW, Cowan KH, Goldsmith ME. Isolation of amplified and overexpressed DNA sequences from adriamycin-resistant human breast cancer cells. Cancer Res. 1987 Oct 1;47(19):5141-8.

  PMID: 2441861 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms; Lung Neoplasms; Ovarian Neoplasms

Interventions

Vinorelbine; tariquidar

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 18, 2000
• First Posted: December 10, 2002
• Study Start: December 1, 1999
• Study Completion: June 1, 2001
• Last Updated: March 4, 2008

Record last verified: 2000-12

Locations

US (1)