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A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas


Phase 1
18 Years
N/A
Not Enrolling
Both
Cancer

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Trial Information

A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicities and maximum tolerated dose

Safety Issue:

Yes

Principal Investigator

Shivaani Kummar, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Medical Oncology Branch

Authority:

United States: Federal Government

Study ID:

010124

NCT ID:

NCT00020579

Start Date:

March 2001

Completion Date:

October 2008

Related Keywords:

  • Cancer
  • 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
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Neuroectodermal Tumors, Primitive
  • Neuroectodermal Tumors, Primitive, Peripheral

Name

Location

National Naval Medical CenterBethesda, Maryland  20889
Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182
NCI - Center for Cancer ResearchBethesda, Maryland  20892