Clinical trial NCT00020579: MS-275 in Treating Patients With Advanced Solid Tumors or Lymphoma
Official title: A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
small intestine lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
primary central nervous system non-Hodgkin lymphoma
intraocular lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
male breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent pancreatic cancer
stage III pancreatic cancer
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage III ovarian epithelial cancer
stage III ovarian germ cell tumor
stage IV ovarian epithelial cancer
stage IV ovarian germ cell tumor
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
recurrent cervical cancer
stage III cervical cancer
stage IVA cervical cancer
stage IVB cervical cancer
recurrent endometrial carcinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma
fallopian tube cancer
primary peritoneal cavity cancer
recurrent uterine sarcoma
stage III uterine sarcoma
stage IV uterine sarcoma
recurrent vaginal cancer
stage III vaginal cancer
stage IVA vaginal cancer
stage IVB vaginal cancer
recurrent vulvar cancer
stage III vulvar cancer
stage IV vulvar cancer
recurrent anal cancer
stage IIIA anal cancer
stage IIIB anal cancer
stage IV anal cancer
recurrent esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
recurrent gastric cancer
stage III gastric cancer
stage IV gastric cancer
recurrent extrahepatic bile duct cancer
unresectable extrahepatic bile duct cancer
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent basal cell carcinoma of the lip
recurrent squamous cell carcinoma of the lip and oral cavity
stage III basal cell carcinoma of the lip
stage III squamous cell carcinoma of the lip and oral cavity
stage IV basal cell carcinoma of the lip
stage IV squamous cell carcinoma of the lip and oral cavity
recurrent lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
stage III lymphoepithelioma of the oropharynx
stage III squamous cell carcinoma of the oropharynx
stage IV lymphoepithelioma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
stage III lymphoepithelioma of the nasopharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage III inverted papilloma of the paranasal sinus and nasal cavity
stage III midline lethal granuloma of the paranasal sinus and nasal cavity
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
metastatic parathyroid cancer
recurrent parathyroid cancer
recurrent salivary gland cancer
stage III salivary gland cancer
stage IV salivary gland cancer
recurrent bladder cancer
recurrent gallbladder cancer
stage III bladder cancer
stage IV bladder cancer
unresectable gallbladder cancer
recurrent renal cell cancer
stage III renal cell cancer
stage IV renal cell cancer
stage III Wilms tumor
stage IV Wilms tumor
stage V Wilms tumor
metastatic transitional cell cancer of the renal pelvis and ureter
recurrent transitional cell cancer of the renal pelvis and ureter
regional transitional cell cancer of the renal pelvis and ureter
anterior urethral cancer
posterior urethral cancer
recurrent urethral cancer
recurrent penile cancer
stage III penile cancer
stage IV penile cancer
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
metastatic osteosarcoma
recurrent osteosarcoma
recurrent adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
classic Kaposi sarcoma
AIDS-related Kaposi sarcoma
recurrent Kaposi sarcoma
stage III cutaneous T-cell non-Hodgkin lymphoma
ciliary body and choroid melanoma, medium/large size
ciliary body and choroid melanoma, small size
extraocular extension melanoma
iris melanoma
recurrent intraocular melanoma
recurrent melanoma
stage III melanoma
stage IV melanoma
extensive stage small cell lung cancer
recurrent non-small cell lung cancer
recurrent small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent thymoma and thymic carcinoma
advanced malignant mesothelioma
recurrent malignant mesothelioma
recurrent adrenocortical carcinoma
stage III adrenocortical carcinoma
stage IV adrenocortical carcinoma
metastatic gastrointestinal carcinoid tumor
recurrent gastrointestinal carcinoid tumor
regional gastrointestinal carcinoid tumor
desmoid tumor
newly diagnosed carcinoma of unknown primary
recurrent carcinoma of unknown primary
undifferentiated carcinoma of unknown primary
carcinoma of the appendix
recurrent metastatic squamous neck cancer with occult primary
untreated metastatic squamous neck cancer with occult primary
recurrent pituitary tumor
adult anaplastic astrocytoma
adult astrocytic tumors
adult diffuse astrocytoma
adult pilocytic astrocytoma
adult anaplastic oligodendroglioma
adult brain stem glioma
adult oligodendroglioma
adult mixed glioma
adult central nervous system germ cell tumor
adult choroid plexus tumor
adult craniopharyngioma
adult anaplastic ependymoma
adult subependymoma
adult medulloblastoma
adult supratentorial primitive neuroectodermal tumor (PNET)
adult ependymoblastoma
adult ependymoma
adult myxopapillary ependymoma
adult anaplastic meningioma
adult meningeal hemangiopericytoma
adult meningioma
adult papillary meningioma
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult pineal parenchymal tumor
recurrent adult brain tumor
stage IV pancreatic cancer
stage III thymoma
stage IVA thymoma
stage IVB thymoma
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase I trial is studying the side effects and best dose of MS-275 in treating patients with advanced solid tumors or lymphoma.

Detailed description: OBJECTIVES:

* Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 in patients with advanced solid tumors or lymphomas.
* Determine the profile of adverse events, including changes in laboratory parameters, in patients treated with this drug.
* Assess the pharmacology and pharmacokinetics of this drug in these patients.
* Design MS-275 regimens with possibly more frequent dose administration based on the pharmacology of MS-275 using the schedule in this study.
* Determine the antineoplastic activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive oral MS-275 once on day 1. Courses repeat every 2 weeks (every 2-week schedule). Alternatively, patients receive oral MS-275 once on days 1, 8, 15, and 22 (weekly schedule). Courses repeat every 6 weeks. Treatment for both schedules continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MS-275 on the every 2-week schedule until the maximum tolerated dose (MTD) is determined. Once the MTD for the every 2-week schedule is determined, patients receive treatment on the weekly schedule as above. The MTD is then determined for the weekly schedule. The MTD for both schedules is defined as the dose preceding that at which at least 2 of up to 6 patients experience dose-limiting toxicity. Once the MTD is determined for the weekly schedule, up to 3 additional patients are accrued to receive MS-275 at the MTD of the weekly schedule.

Disease status is assessed every 3 months.

PROJECTED ACCRUAL: A total of 50-75 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignancy that is metastatic or unresectable and for which no effective standard curative or palliative therapy exists
* Brain metastases allowed provided both of the following criteria are met:

  * Received treatment for the brain metastases
  * Stable for ≥ 6 months without steroids or antiseizure medications

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2 OR
* Karnofsky 50-100%

Life expectancy:

* More than 3 months

Hematopoietic:

* WBC at least 3,000/mm\^3
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN) (≤ 3 mg/dL for patients with Gilbert's syndrome)
* AST/ALT no greater than 2.5 times ULN
* Albumin at least 75% of lower limit of normal

Renal:

* Creatinine normal OR
* Creatinine clearance at least 60 mL/min

Cardiovascular:

* Cardiac ejection fraction normal by MUGA
* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Adequate oral intake
* No weight loss of more than 10% of actual body weight within the past 2 months
* No history of allergic reaction to compounds of similar chemical or biological composition to study drug
* No other uncontrolled illness
* No ongoing or active infection
* No seizure disorder
* No psychiatric illness or social situation that would preclude study compliance
* No acute or chronic gastrointestinal conditions (e.g., peptic ulcer or colitis) within the past 2 months that would interfere with drug tolerance or absorption
* Willing and able to self-administer and document doses of MS-275

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 4 weeks since prior anticancer vaccine therapy and recovered
* No concurrent immunotherapy

Chemotherapy:

* At least 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
* At least 8 weeks since prior UCN-01 and recovered
* No concurrent chemotherapy

Endocrine therapy:

* At least 4 weeks since prior anticancer hormonal therapy (except gonadotropin-releasing hormone \[GnRH\] agonists) and recovered
* Concurrent corticosteroids for physiological replacement, as antiemetic therapy, or for an ongoing condition allowed

  * Must be on a stable dose during the past 4 weeks
* No concurrent anticancer hormonal therapy except GnRH agonists for noncastrated patients with prostate cancer

Radiotherapy:

* At least 4 weeks since prior anticancer radiotherapy and recovered
* No concurrent radiotherapy

  * Concurrent localized radiotherapy to a single lesion allowed if the patient achieves at least a partial response

Surgery:

* At least 3 weeks since prior major surgery

Other:

* No other concurrent investigational or commercial antineoplastic therapies

Primary outcomes:
measure: Dose-limiting toxicities and maximum tolerated dose
measure: Pharmacology and pharmacokinetics
Secondary outcomes:
measure: Acetylation of histones in peripheral blood
measure: Tumor response by CT scan every 12 weeks
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Naval Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Bethesda
country: United States
facility: NCI - Center for Cancer Research
state: Maryland
Study officials:
affiliation: NCI - Medical Oncology Branch
name: Shivaani Kummar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ryan QC, Headlee D, Sparreboom A, et al.: A phase I trial of an oral histone deacetylase inhibitor, MS-275, in advanced solid tumor and lymphoma patients. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-802, 2003.