Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00071058
Status:
COMPLETED
Last Update Posted:
2012-09-18
First Post:
2003-10-09
Brief Title:
Surgery Plus Chemotherapy Doxorubicin Vincristine and Etoposide Mitotane and Tariquidar to Treat Adrenocortical Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Study of Combination Chemotherapy Surgical Resection in the Tx of Adrenocortical Cancer Mitotane Continuous Infusion Doxorubicin Vincristine Etoposide wthe P-glycoprotein Antagonist Tariquidar XR9576 Before After Surgical Resection
Status:
COMPLETED
Status Verified Date:
2012-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the safety and effectiveness of treating adrenocortical cancer with combination chemotherapy using doxorubicin vincristine and etoposide in addition to the drugs mitotane and tariquidar and when possible surgery Adrenocortical cancer cells have a large amount of a protein called P-glycoprotein that pumps anti-cancer drugs out of the cells decreasing their effectiveness Continuous infusions of doxorubicin vincristine and etoposide may improve chemotherapy results by blocking the P-glycoprotein pump as may use of tariquidar an experimental drug that is known to block the P-glycoprotein pump
Patients 18 years of age and older with adrenocortical cancer that has recurred spread or cannot be treated surgically may be eligible for this study Candidates will be screened with a medical history and physical examination review of pathology slides blood tests electrocardiogram EKG imaging tests including computed tomography CT of the chest abdomen and pelvis chest x-ray and possibly a bone scan or other imaging tests needed to evaluate the cancer urine studies and an echocardiogram Also a biopsy removal of a small sample of tumor tissue may be required if a specimen is not available to confirm the cancer
Participants will undergo the following tests and procedures
Tumor biopsy Before starting chemotherapy a small piece of tumor is removed to study the P-glycoprotein pump and to determine the tumor genetics
Blood draw Blood is drawn before treatment begins to establish baseline levels for future blood tests
Central venous catheter placement A specially trained physician places a plastic tube into a major vein in the chest The tube is used to give the study drugs and other medications and to withdraw blood samples It can stay in the body for months or be removed after each treatment is completed The tube placement is done under a local anesthetic in the radiology department or operating room
Chemotherapy Treatment cycles are 21 days Doxorubicin vincristine and etoposide are given through the central venous catheter by an infusion pump continuously over 96 hours starting day 1 of each cycle The dose of these drugs may be increased or decreased from cycle to cycle based on side effects Mitotane is given in pill form starting day 1 of cycle 1 and is taken every day throughout the entire study The mitotane dose is gradually increased as long as the side effects are tolerable Tariquidar is given through the central venous catheter as a 30-minute infusion on days 1 and 3 of every cycle The tariquidar dose remains the same throughout the study Treatment will continue for two cycles after all the cancer is gone or until surgery is done to remove some or all of the remaining cancer or if surgery is not an option until the cancer has grown to where it is defined as progressive disease
Nuclear scans A nuclear scan is done before treatment begins and again on day 1 or day 3 of the first treatment cycle after administration of tariquidar to evaluate the P glycoprotein response to treatment
Computed tomography CT scans These scans are done every two treatment cycles to follow disease progress
Surgery Surgery to remove areas of cancer may be considered at any point during the study including before beginning treatment if it is deemed beneficial Treatment with the study drugs will begin or resume after surgery The length of treatment will depend on the response to treatment before the surgery and on whether there is any cancer remaining after the surgery
Patients 18 years of age and older with adrenocortical cancer that has recurred spread or cannot be treated surgically may be eligible for this study Candidates will be screened with a medical history and physical examination review of pathology slides blood tests electrocardiogram EKG imaging tests including computed tomography CT of the chest abdomen and pelvis chest x-ray and possibly a bone scan or other imaging tests needed to evaluate the cancer urine studies and an echocardiogram Also a biopsy removal of a small sample of tumor tissue may be required if a specimen is not available to confirm the cancer
Participants will undergo the following tests and procedures
Tumor biopsy Before starting chemotherapy a small piece of tumor is removed to study the P-glycoprotein pump and to determine the tumor genetics
Blood draw Blood is drawn before treatment begins to establish baseline levels for future blood tests
Central venous catheter placement A specially trained physician places a plastic tube into a major vein in the chest The tube is used to give the study drugs and other medications and to withdraw blood samples It can stay in the body for months or be removed after each treatment is completed The tube placement is done under a local anesthetic in the radiology department or operating room
Chemotherapy Treatment cycles are 21 days Doxorubicin vincristine and etoposide are given through the central venous catheter by an infusion pump continuously over 96 hours starting day 1 of each cycle The dose of these drugs may be increased or decreased from cycle to cycle based on side effects Mitotane is given in pill form starting day 1 of cycle 1 and is taken every day throughout the entire study The mitotane dose is gradually increased as long as the side effects are tolerable Tariquidar is given through the central venous catheter as a 30-minute infusion on days 1 and 3 of every cycle The tariquidar dose remains the same throughout the study Treatment will continue for two cycles after all the cancer is gone or until surgery is done to remove some or all of the remaining cancer or if surgery is not an option until the cancer has grown to where it is defined as progressive disease
Nuclear scans A nuclear scan is done before treatment begins and again on day 1 or day 3 of the first treatment cycle after administration of tariquidar to evaluate the P glycoprotein response to treatment
Computed tomography CT scans These scans are done every two treatment cycles to follow disease progress
Surgery Surgery to remove areas of cancer may be considered at any point during the study including before beginning treatment if it is deemed beneficial Treatment with the study drugs will begin or resume after surgery The length of treatment will depend on the response to treatment before the surgery and on whether there is any cancer remaining after the surgery
Detailed Description:
Adrenocortical cancer ACC is a rare tumor that is optimally treated with surgical resection However many patients present with unresectable disease and relapses are common after surgical resection creating a need for more effective systemic therapies Several investigators have reported responses to a variety of chemotherapy agents without a clear improvement in overall survival A possible explanation for these disappointing results is the high levels of expression of P-glycoprotein Pgp seen in a majority of adrenocortical cancers Pgp a membrane protein that can function as a drug efflux pump lowering the intracellular concentrations of various drugs has been implicated as a mechanism of drug resistance
A prior National Cancer Institute NCI study referred to as MAVE tried to improve response rates by using a combined modality approach with chemotherapy and surgery Prior in vitro studies had shown that mitotane inhibited Pgp and that continuous exposure to doxorubicin and vincristine was more effective at overcoming Pgp-mediated resistance than the same drugs given on an intermittent schedule The MAVE study used daily oral mitotane with infusional doxorubicin vincristine and etoposide prior to tumor resection in patients with resectable or potentially resectable tumors The results showed an overall response rate of 19 including minor responses and an overall median survival of 135 months These results were similar to those reported with previous regimens in adrenocortical cancer ACC A possible explanation for the failure to achieve a higher response rate may be that mitotane was unable to inhibit Pgp Although the serum levels of mitotane achieved in patients had been shown to block Pgp in vitro inhibition of Pgp in patients was not accomplished as documented by a validated surrogate assay using Pgp-expressing CD56 cells and the Pgp substrate rhodamine Thus the question of whether Pgp inhibition would improve response rates remains unanswered
This trial will attempt to answer the latter question by using an agent tariquidar XR9576 which has been proven to inhibit Pgp in humans with minimal toxicity alone or in combination with chemotherapy Tariquidar will be used with the regimen from the prior MAVE study in an effort to improve response rates and overall survival in patients with ACC whose options at this time are limited
A prior National Cancer Institute NCI study referred to as MAVE tried to improve response rates by using a combined modality approach with chemotherapy and surgery Prior in vitro studies had shown that mitotane inhibited Pgp and that continuous exposure to doxorubicin and vincristine was more effective at overcoming Pgp-mediated resistance than the same drugs given on an intermittent schedule The MAVE study used daily oral mitotane with infusional doxorubicin vincristine and etoposide prior to tumor resection in patients with resectable or potentially resectable tumors The results showed an overall response rate of 19 including minor responses and an overall median survival of 135 months These results were similar to those reported with previous regimens in adrenocortical cancer ACC A possible explanation for the failure to achieve a higher response rate may be that mitotane was unable to inhibit Pgp Although the serum levels of mitotane achieved in patients had been shown to block Pgp in vitro inhibition of Pgp in patients was not accomplished as documented by a validated surrogate assay using Pgp-expressing CD56 cells and the Pgp substrate rhodamine Thus the question of whether Pgp inhibition would improve response rates remains unanswered
This trial will attempt to answer the latter question by using an agent tariquidar XR9576 which has been proven to inhibit Pgp in humans with minimal toxicity alone or in combination with chemotherapy Tariquidar will be used with the regimen from the prior MAVE study in an effort to improve response rates and overall survival in patients with ACC whose options at this time are limited
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-0011 | None | None | None |