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A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Subjects With Locally Advanced, Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC) (IND 71976)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Salivary Gland Cancer, Salivary Gland Adenoid Cystic Carcinoma, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Salivary Gland Cancer, Stage IV Adenoid Cystic Carcinoma of the Oral Cavity, Stage IV Salivary Gland Cancer, Tongue Cancer

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Trial Information

A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Subjects With Locally Advanced, Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC) (IND 71976)


PRIMARY OBJECTIVES:

I. To evaluate the efficacy by means of response rate (based on RECIST 1.1 criteria) of
vorinostat in the treatment of patients with locally advanced, recurrent or metastatic
adenoid cystic carcinoma (ACC).

SECONDARY OBJECTIVES:

I. To characterize the safety and tolerability of vorinostat in this patient population.

II. To assess the time to tumor response (TTR). III. To assess the response duration (RD).
IV. To evaluate progression free survival (PFS). V. To assess overall survival (OS).

TERTIARY OBJECTIVES:

I. To assess the association between a metabolic response by PET/CT after one cycle of
chemotherapy and subsequent best tumor response according to standard anatomic response
evaluation criteria (RECIST).

II. To assess the association between a metabolic response by PET/CT after the first and
second chemotherapy cycle and PFS.

III. To assess the association between response to vorinostat treatment and biomarkers such
as c-kit, HER2/neu, EGFR, p21, p16, p53, c-myb, TBP2 and HR23B on tumor paraffin blocks.

IV. To assess the association between response to vorinostat treatment and genomic
biomarkers in tumor tissue.

V. To characterize molecular mechanisms of vorinostat response in ACC and identify novel
therapeutic strategies.

VI. To develop a series of primary tumor grafts from trial participants in support of future
ACC research and experimental therapeutics.

VII. To assess the association between response to vorinostat treatment and detection of the
unique ACC translocation t (6;9) by FISH analysis.

OUTLINE:

Patients receive oral vorinostat once daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 6 months.


Inclusion Criteria:



- Patients must have histologically or cytologically confirmed locally advanced,
recurrent or metastatic adenoid cystic carcinoma

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm by chest x-ray, as >= 10 mm with CT scan, or >= 10 mm with calipers by clinical
exam; all tumor measurements must be recorded in millimeters (or decimal fractions of
centimeters)

- Patients must have locally advanced and/or recurrent and/or metastatic disease not
amenable to potentially curative surgery or radiotherapy. Any prior number of
chemotherapy regimens is allowed; a minimum of at least 4 weeks since prior
chemotherapy or radiation therapy should have elapsed, 6 weeks if the last regimen
included BCNU or mitomycin C

- Life expectancy of greater than 12 weeks

- ECOG performance status 0-2 (Karnofsky >= 60%)

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits (WNL)

- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal (ULN)

- Creatinine within normal institutional limits OR

- Creatinine clearance >= >60 mL/min/1.73 m^2 for patients with creatinine levels above
institutional normal

- Eligibility of patients receiving any medications or substances known to affect or
with the potential to affect the activity or pharmacokinetics of vorinostat will be
determined following review of their case by the principal investigator

- No other diagnosis of malignancy unless non-melanoma skin cancer, carcinoma in situ
of the cervix, or a malignancy diagnosed >= 5 years previously and currently with no
evidence of disease; HOWEVER - if the patient has had a previously diagnosed stage
I/II malignancy of another type, consideration for recruitment may be made by the
CTEP senior investigator after discussion with local PI and patient's physician

- Confirmed availability of tumor tissue (either fresh or from paraffin block) from the
primary tumor or metastatic site to be available to use on correlative studies

- The effects of vorinostat on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason and because HDAC inhibitors are known
to be teratogenic, women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
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

- Ability to understand and the willingness to sign a written informed consent document

- If the patient's tumor can be easily accessed, a pre-treatment biopsy will be
mandatory

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier;
more than 21 days from major surgery should have elapsed before the first dose of the
study drug

- Patients may not be receiving any other investigational agents or have received
vorinostat in the past; patients should not have taken valproic acid for at least 4
weeks prior to enrollment

- Inability to take oral medications on a continuous basis

- Patients with active brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events; patients with previous brain metastases will be eligible if condition is
treated and stable for >= 1 month

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to SAHA

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study because SAHA is a HDAC inhibitor agent
with the potential for teratogenic or abortifacient effects; because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with vorinostat, breastfeeding should be discontinued if the
mother is treated with vorinostat

- Patient is unable or unwilling to abide by the study protocol and to cooperate fully
with the investigator or designee

- Patient on current therapy with enzyme-inducing anticonvulsants

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response according to RECIST 1.1 criteria

Outcome Time Frame:

Up to 180 days

Safety Issue:

No

Principal Investigator

Patricia LoRusso

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02981

NCT ID:

NCT01175980

Start Date:

August 2010

Completion Date:

Related Keywords:

  • Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
  • Recurrent Salivary Gland Cancer
  • Salivary Gland Adenoid Cystic Carcinoma
  • Stage III Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage III Salivary Gland Cancer
  • Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage IV Salivary Gland Cancer
  • Tongue Cancer
  • Carcinoma
  • Carcinoma, Adenoid Cystic
  • Tongue Neoplasms
  • Salivary Gland Neoplasms

Name

Location

Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201