SWOG clinical trial number
E1303
Phase II Trial of PS-341 (NSC-681239) Followed by the Addition of Doxirubicin at Progression in Advanced Adenoid Cystic Carcinoma of the Head and Neck
Closed
Research committees
Head and Neck Cancer
Eligibility Criteria Expand/Collapse
Step 1 (Arm A)
Pts must have locally advanced, recurrent, or metastatic adenoid cystic carcinoma of the head and neck, which is considered incurable by known therapies. Pts must have histologically confirmed adenoid cystic cancer of the H&N. Patients may have any number of prior therapies. (Patients with prior history of high-dose chemo for bone marrow transplantation will be excluded.). Must not have any prior anthracyclines (doxorubicin, epirubicin, daunorubicin, idarubicin) or mitoxantrone. Pts must have unidimensionally measurable disease. Must have MUGA scan showing LVEF at or above the institutional lower limits of normal. ECOG PS = 0 - 2. Must not have currently stable disease (by RECIST criteria) for > 9 months. Within two wks prior to reg: ANC ≥ 1,500/µL; plts ≥ 100,000/µL; total bili w/i normal institutional limits (pts with abnormal bili will be excluded from the study); SGOT/ SGPT ≤ 2.5 X IULN; creat w/i normal institutional limits or CrCl ≥ 60 mL/min/1.73 m2 for pts w/ creat levels above institutional normal. Must not have received chemo or investigational drugs w/i four wks prior to study entry (six weeks for nitrosoureas or mitomycin C). At least three wks must have elapsed between surg and/or RT and study entry. No prior invasive malignancy unless the disease-free interval is 5 years or more. Pts w/ non-melanoma skin cancers and in situ cervical carcinoma are eligible for therapy. Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception. The effects of PS-341 on the developing human fetus at the recommended therapeutic dose are unknown. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Pregnant women are excluded from this study because PS-341 is an agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to tx of the mother with PS-341, breastfeeding should be d/c if the mother is treated with PS-341. All females of childbearing potential must have a blood test or urine study w/i 2 wks prior to reg to rule out pregnancy. Pts w/ known brain mets will be excluded from the study. Must not have h/o allergic reactions attributed to compounds of similar chemical or biologic composition to PS-341. Must not have h/o congestive heart failure; must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pts with documented HIV positive status are excluded. Pts must not have any pre-existing neuropathy of grade > 1.
Step 2 (Arm B)
Pts must have documentation of progression of disease on PS-341. Pts must register and start doxorubicin at least ten days and a maximum of four weeks from the last PS-341 administration. Must have ECOG PS = 0 - 2. Within two weeks prior to registration: ANC ≥ 1,500/µL; plts ≥ 100,000/µL; total bili w/i normal institutional limits (pts with abnormal bili will be excluded from the study); SGOT/SGPT ≤ 2.5 X IULN; creat w/i normal institutional limits or CrCl ≥ 60 mL/min/1.73 m2 for pts w/ creat levels above institutional normal. Pts must have no evidence of congestive heart failure.
Pts must have locally advanced, recurrent, or metastatic adenoid cystic carcinoma of the head and neck, which is considered incurable by known therapies. Pts must have histologically confirmed adenoid cystic cancer of the H&N. Patients may have any number of prior therapies. (Patients with prior history of high-dose chemo for bone marrow transplantation will be excluded.). Must not have any prior anthracyclines (doxorubicin, epirubicin, daunorubicin, idarubicin) or mitoxantrone. Pts must have unidimensionally measurable disease. Must have MUGA scan showing LVEF at or above the institutional lower limits of normal. ECOG PS = 0 - 2. Must not have currently stable disease (by RECIST criteria) for > 9 months. Within two wks prior to reg: ANC ≥ 1,500/µL; plts ≥ 100,000/µL; total bili w/i normal institutional limits (pts with abnormal bili will be excluded from the study); SGOT/ SGPT ≤ 2.5 X IULN; creat w/i normal institutional limits or CrCl ≥ 60 mL/min/1.73 m2 for pts w/ creat levels above institutional normal. Must not have received chemo or investigational drugs w/i four wks prior to study entry (six weeks for nitrosoureas or mitomycin C). At least three wks must have elapsed between surg and/or RT and study entry. No prior invasive malignancy unless the disease-free interval is 5 years or more. Pts w/ non-melanoma skin cancers and in situ cervical carcinoma are eligible for therapy. Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception. The effects of PS-341 on the developing human fetus at the recommended therapeutic dose are unknown. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Pregnant women are excluded from this study because PS-341 is an agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to tx of the mother with PS-341, breastfeeding should be d/c if the mother is treated with PS-341. All females of childbearing potential must have a blood test or urine study w/i 2 wks prior to reg to rule out pregnancy. Pts w/ known brain mets will be excluded from the study. Must not have h/o allergic reactions attributed to compounds of similar chemical or biologic composition to PS-341. Must not have h/o congestive heart failure; must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pts with documented HIV positive status are excluded. Pts must not have any pre-existing neuropathy of grade > 1.
Step 2 (Arm B)
Pts must have documentation of progression of disease on PS-341. Pts must register and start doxorubicin at least ten days and a maximum of four weeks from the last PS-341 administration. Must have ECOG PS = 0 - 2. Within two weeks prior to registration: ANC ≥ 1,500/µL; plts ≥ 100,000/µL; total bili w/i normal institutional limits (pts with abnormal bili will be excluded from the study); SGOT/SGPT ≤ 2.5 X IULN; creat w/i normal institutional limits or CrCl ≥ 60 mL/min/1.73 m2 for pts w/ creat levels above institutional normal. Pts must have no evidence of congestive heart failure.