Ignite Creation Date:
2024-05-05 @ 12:07 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00248248
Status:
COMPLETED
Last Update Posted:
2011-10-12
First Post:
2005-11-01
Brief Title:
DOXIL for Consolidation Therapy in Ovarian Cancer
Sponsor:
Southeastern Gynecologic Oncology
Organization:
Southeastern Gynecologic Oncology
Study Overview
Official Title:
A Phase II Non-randomized Study of DOXIL Consolidation Treatment for Ovarian Cancer Cancer of the Fallopian Tube or Peritoneal Carcinoma
Status:
COMPLETED
Status Verified Date:
2011-10
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:
The primary objective for this study is to evaluate the development frequency and severity of hand foot syndrome HFS in ovarian cancer subjects treated with Doxil as consolidation therapy on an every two week schedule
The secondary objective for this study is to assess one-year progression free survival rate PFS
The secondary objective for this study is to assess one-year progression free survival rate PFS
Detailed Description:
While the majority of subjects with advanced ovarian cancer will respond well to the initial chemotherapy regimen of taxolplatinum these responses are generally of limited duration Even women who have a surgically defined complete response to initial chemotherapy have 50 recurrence rate in Stage III disease Once ovarian cancer has recurred it is rare that cure is possible therefore there is a critical need to define new therapeutic strategies in the treatment of ovarian cancer Consolidation chemotherapy is one possible strategy The strategy behind consolidation chemotherapy institutes second-line chemotherapy immediately following a clinical response but before evidence of recurrence This strategy has gained popularity with many oncologists secondary to the results of GOG 178 a large study by the Southwest Oncology Group and the Gynecologic Oncology Group GOG 178 set out to explore both efficacy and patient tolerability in the consolidation setting Moreover the objective of the GOG 178 study was to compare two different durations of consolidation treatment using taxol consolidation in clinically NED ovarian cancer subjects following primary chemotherapy of carbotaxol The results of GOG178 suggested that a longer course 12 vs 3 cycles of paclitaxel gave subjects a longer median progression-free survival 28 vs 21 months This trial was closed early due to a statistically improved PFS in subjects receiving 12-month regimen of paclitaxel versus the 3 month regimen Unfortunately we will never definitively learn if this improved PFS translates to improved survival for ovarian cancer patients A limitation of this regimen is the cumulative and sometimes irreversible side effect of neuropathy Doxil has been selected in this consolidation trial due to documented success in second- line setting with ovarian cancer subjects without long term negative sequelae such as neuropathy The anthracycline antibiotic doxorubicin has a broad spectrum of antineoplastic action and a correspondingly widespread degree of clinical use In addition to its role in the treatment of ovarian cancer doxorubicin is indicated in the treatment of Hodgkins disease and non-Hodgkins lymphoma hepatocellular and gastric carcinoma small cell cancer of the lung soft tissue and bone sarcomas as well as cancer of the breast bladder and thyroid Unfortunately toxicity limits the therapeutic activity of doxorubicin and may preclude adequate dosing
The conventional formulation of the drug is rapidly cleared from the bloodstream and has a very large volume of distribution which may contribute to the drugs toxicity High cumulative doses of doxorubicin generally must be avoided because of the potential for cardiotoxicity while individual doses are often limited by myelosuppression Alopecia typically develops and persists throughout treatment Severe acute nausea and vomiting stomatitis and esophagitis are additional adverse effects of doxorubicin that may necessitate dose-reduction or discontinuation of the drug A doxorubicin formulation with improved tolerability might increase the drugs therapeutic ratio and thus enhance its efficacy
Liposomal encapsulation of doxorubicin may reduce both the nonspecific drug delivery to normal tissues as well as the high peak plasma levels of free drug responsible for its toxicity At the same time a liposomal formulation may deliver doxorubicin to tumors with improved specificity Doxil is a doxorubicin formulation in which the drug is encapsulated in liposomes Stealthâ liposomes that escape instant recognition and uptake by the mononuclear phagocyte system As a result the formulation has a long circulation time and the liposomes can eventually become extravasated through the abnormally permeable vessels characteristic of many tumors Once concentrated in tumors the liposomes of Doxil can deliver high levels of doxorubicin to malignant cells without affecting normal tissue1
Doxil is approved by the FDA for use in subjects with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy and in subjects with HIV Kaposis Sarcoma Doxil established efficacy as a single agent in recurrent ovarian cancer as a result of three open-label single-arm clinical studies of 176 subjects with metastatic ovarian cancer Subjects in these studies received Doxil at 50mgm2 infused over one hour every 3 or 4 weeks for 3-6 cycles or longer in the absence of dose-limiting toxicity or progression of disease Doxil has been used for several years as a 2nd line chemotherapy agent In the randomized Phase III study of subjects with recurrent ovarian cancer by Gordon et al there was an 18 reduction in the risk of death for subjects treated with Doxil median survival 627weeks compared to topotecan median survival 597 weeks In platinum sensitive subjects who recurred after more than six months the reduction in risk of death was even more dramatic a 30 reduction was noted in the subjects who received Doxil median survival 1079 weeks versus topotecan median survival 701 weeks In this trial Doxil 50mgm2 was administered every 28 days resulting in 234 of the subjects with grade 3 or 4 hand foot syndrome HFS 4 Management of this side effect included increasing the dosage interval andor decreasing the dose by 25 Today Doxil 40mgm2 every 28 days is commonly used for treatment of recurrent ovarian cancer Rose et al reported their results from a retrospective review noting the 40mgm2 dose every 28 days minimizes toxicity without sacrificing efficacy6
Experience has taught us this toxicity can be minimized with patient education focusing on alteration of activities in the day preceding and 3-5 days follow drug administration Other side effects such as bone marrow suppression alopecia nausea vomiting and fatigue are minimal There have been several small trials using weekly and bi-weekly Doxil in cancer patients including breast gastric pancreatic and colon cancer in an attempt to reduce the incidence of hand foot syndrome with encouraging results
This study will evaluate the efficacy of Doxil in clinically NED ovarian cancer subjects following standard platinumtaxane based therapy Applying every two-week dosing of Doxil 20mgm2 as this is expected to minimize the most problematic side effect HFS
The conventional formulation of the drug is rapidly cleared from the bloodstream and has a very large volume of distribution which may contribute to the drugs toxicity High cumulative doses of doxorubicin generally must be avoided because of the potential for cardiotoxicity while individual doses are often limited by myelosuppression Alopecia typically develops and persists throughout treatment Severe acute nausea and vomiting stomatitis and esophagitis are additional adverse effects of doxorubicin that may necessitate dose-reduction or discontinuation of the drug A doxorubicin formulation with improved tolerability might increase the drugs therapeutic ratio and thus enhance its efficacy
Liposomal encapsulation of doxorubicin may reduce both the nonspecific drug delivery to normal tissues as well as the high peak plasma levels of free drug responsible for its toxicity At the same time a liposomal formulation may deliver doxorubicin to tumors with improved specificity Doxil is a doxorubicin formulation in which the drug is encapsulated in liposomes Stealthâ liposomes that escape instant recognition and uptake by the mononuclear phagocyte system As a result the formulation has a long circulation time and the liposomes can eventually become extravasated through the abnormally permeable vessels characteristic of many tumors Once concentrated in tumors the liposomes of Doxil can deliver high levels of doxorubicin to malignant cells without affecting normal tissue1
Doxil is approved by the FDA for use in subjects with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy and in subjects with HIV Kaposis Sarcoma Doxil established efficacy as a single agent in recurrent ovarian cancer as a result of three open-label single-arm clinical studies of 176 subjects with metastatic ovarian cancer Subjects in these studies received Doxil at 50mgm2 infused over one hour every 3 or 4 weeks for 3-6 cycles or longer in the absence of dose-limiting toxicity or progression of disease Doxil has been used for several years as a 2nd line chemotherapy agent In the randomized Phase III study of subjects with recurrent ovarian cancer by Gordon et al there was an 18 reduction in the risk of death for subjects treated with Doxil median survival 627weeks compared to topotecan median survival 597 weeks In platinum sensitive subjects who recurred after more than six months the reduction in risk of death was even more dramatic a 30 reduction was noted in the subjects who received Doxil median survival 1079 weeks versus topotecan median survival 701 weeks In this trial Doxil 50mgm2 was administered every 28 days resulting in 234 of the subjects with grade 3 or 4 hand foot syndrome HFS 4 Management of this side effect included increasing the dosage interval andor decreasing the dose by 25 Today Doxil 40mgm2 every 28 days is commonly used for treatment of recurrent ovarian cancer Rose et al reported their results from a retrospective review noting the 40mgm2 dose every 28 days minimizes toxicity without sacrificing efficacy6
Experience has taught us this toxicity can be minimized with patient education focusing on alteration of activities in the day preceding and 3-5 days follow drug administration Other side effects such as bone marrow suppression alopecia nausea vomiting and fatigue are minimal There have been several small trials using weekly and bi-weekly Doxil in cancer patients including breast gastric pancreatic and colon cancer in an attempt to reduce the incidence of hand foot syndrome with encouraging results
This study will evaluate the efficacy of Doxil in clinically NED ovarian cancer subjects following standard platinumtaxane based therapy Applying every two-week dosing of Doxil 20mgm2 as this is expected to minimize the most problematic side effect HFS
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