GOG PROTOCOL #209. David Miller, MD, Gini Fleming, MD, Richard Zaino, MD, and David Cella, PhD

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1 GOG PROTOCOL #209 PROTOCOL Study Chairs Statistician Data Coordinator Randomized Phase III Trial of Doxorubicin/Cisplatin/Paclitaxel and G-CSF Versus Carboplatin/Paclitaxel in Patients with Stage III and IV or Recurrent Endometrial Cancer David Miller, MD, Gini Fleming, MD, Richard Zaino, MD, and David Cella, PhD Virginia Filiaci, MA and Helen Huang, MS (QOL) Patricia Brehm, CCRP Activated 8/25/03 Revised 3/15/04, 5/2/05, 8/29/05, 11/21/05, 4/17/06, Closed 4/20/09 10/30/06, 3/26/07, 2/11/08, 7/28/08 Purpose To determine if the combination of carboplatin and paclitaxel (TC) chemotherapy is therapeutically equivalent to the combination of doxorubicin, cisplatin and paclitaxel (TAP) chemotherapy with regards to survival. To determine if estrogen/progesterone receptor status provides prognostic information in patients treated with chemotherapy. To assess whether combination TC chemotherapy is superior to combination TAP chemotherapy with regards to toxicity profile, specifically neurotoxicity and infection. To measure differences in patient-reported neurotoxicity and quality of life among the regimens. Eligibility Patients must have primary Stage III, IV, or recurrent endometrial carcinoma whose potential for cure by radiation therapy or surgery alone or in combination is very poor. Pathological confirmation and Estrogen Receptor (ER)/Progesterone Receptor (PR) status of the primary tumor is mandatory. Patients may not have received prior cytotoxic chemotherapy, including chemotherapy used for radiation sensitization. Patients may have received prior radiation therapy, hormonal therapy or therapy with biologic agents, but such therapies must be discontinued prior to entry on this study. At least four weeks should have elapsed since completion of RT involving the whole pelvis or over 50% of the spine. Patients must have adequate end-organ function. Patients must have a GOG Performance Status of 0, 1, or 2. Patients in whom both radiation and chemotherapy is planned must receive radiation prior to entry to this study. At least four weeks should have elapsed since completion of RT involving the whole pelvis or over 50% of the spine.

2 PATIENT ACCESSION DATA ENT EXCL ENT EXCL 001 RPCI WASH U ALABAMA MEMORIAL DUKE COOPER ABINGTON COLUMBUS W REED ANDERSON WAYNE ST MASS MINN FOX CHASE MT SINAI WCC-UNEV NORTHWESTN OKLAHOMA MISS VIRGINIA COLORADO CHICAGO UCLA MAYO U WASH CASE WEST PENN TAMPA HERSHEY GYNONCNET CINN YALE NC GOGJAPAN IOWA WISCONSIN DALLAS CTSU INDIANA GALVESTON W FOREST WOM & INF IRVINE CENT CONN RUSH GA CORE MAGEE WESTRNMICH SUNY-DWN AURORA HC KENTUCKY CCOP NEW MEXICO OTHERS CLEV SUNY-SB 31 1 TOTAL Regimen Number Entered Number Ineligible Number Eligible P Q Total Path review pending in 157; Gyn review pending in 634. Ineligible Patients by Regimen Regimen Total Reason P Q Wrong stage Second primary Wrong cell type Wrong primary Inadequate path materials No tumor at entry Prior chemotherapy Primary not documented Consent withdrawn Total As of the January 2008 report, there are no reports of patients who were assigned to Regimen I and had to cross over to Regimen II due to pretreatment left ventricular ejection fraction <50%. There was no need to inflate the sample size due to crossover.

3 ANALYSIS CLINICAL RESEARCH Patient Characteristics Regimen P Regimen Q Characteristic N % N % Age Group Ethnicity Hispanic or Latino Non-Hispanic Unknown/Not specified Race White Black/African American Asian American Indian/Alaskan Native Native Hawaiian/Pacific Islander Other Unknown Performance Status Cell Type Adenosquamous Adenocarcinoma, NOS Clear Cell Endometrioid Mucinous Mixed Epithelial Squamous Undifferentiated Villoglandular Serous Stage III IV Recurrent Stratification Stratum Stratum Stratum Stratum

4 Estrogen and Progesterone Receptors in Primary Tissue Regimen P Regimen Q Receptor Status N % N % Estrogen-negative Estrogen-positive Estrogen-pending Estrogen-not done Progesterone-negative Progesterone-positive Progesterone-pending Progesterone-not done Treatment Reason Off Study Treatment By Randomized Treatment Regimen P Regimen Q Reason off therapy N % N % Total Still receiving treatment Completed regimen Disease Progression Patient Refused Toxicity Death Other Adverse Events The table below summarizes the adverse effects of therapy for 1255 patients considered evaluable for toxicity. All toxicity is graded according to CTCAE v2.0. Adverse Effect Regimen P Regimen Q Total Total Leukopenia Neutropenia Thrombocytopenia Anemia Hemolysis Other Hematologic Allergy Auditory Ventricular Function Cardiovascular Thrombosis/Embolism Coagulation Constitutional Fatigue Fever, No Neutropenia Alopecia Rash/Desquamation Dermatologic Endocrine Gastrointestinal

5 Adverse Effect Regimen P Regimen Q Total Total Nausea Vomiting Diarrhea Anorexia Stomatitis Genitourinary/Renal Creatinine Hemorrhage Hepatic Infection/Fever Febrile Neutropenia Infection w/o Neutropenia Infection w/ Neutropenia Lymphatics Metabolic Musculoskeletal Neurologic Neuromotor Sensory neuropathy Ocular/Visual Pain Myalgia Arthralgia Pulmonary Sexual nd Primary Second malignancies: Acute Leukemia (2), Melanoma (1), Bladder (1). Deaths attributable to treatment are described in the Progression and Survival section. Progression and Survival Twenty deaths have been at least partially attributed to study treatment: sepsis with neutropenia (9); aspiration (1); renal failure (3); thrombocytopenia, anemia, hemorrhage (1); infection, possible pulmonary embolism (1); leukopenia (1); sepsis and pneumonia (1); non-septic neutropenia (1); sepsis post surgically treated perforation (1); thromboembolism (1).

6 ANALYSIS QUALITY OF LIFE Assessment Status The following table summarized quality of life assessments for 540 eligible patients who entered study prior to 3/26/07. Time of Assessment Received & Valid Insufficient Answers Missed* Delinquent* Total Due Cumulative Deaths No. % No. % No. % No. % No. No. Prior to randomization wks post randomization wks post randomization wks post randomization *: Missed: Forms missed due to patients illness, refusal, loss of contact, etc. Delinquent: Forms missed due to institutional error or missed without reasons reported. CONCLUSIONS Too early. PUBLICATIONS None.