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A Phase 1 Study of Vorinostat in Combination With Paclitaxel and Carboplatin in Solid Tumors (With Focus on Upper Aerodigestive Cancers) in Persons With HIV Infection


Phase 1
18 Years
N/A
Not Enrolling
Both
HIV Infection, Recurrent Anal Cancer, Recurrent Breast Cancer, Recurrent Esophageal Cancer, Recurrent Gastric Cancer, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Non-small Cell Lung Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Salivary Gland Squamous Cell Carcinoma, Stage IV Anal Cancer, Stage IV Breast Cancer, Stage IV Esophageal Cancer, Stage IV Gastric Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Salivary Gland Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Verrucous Carcinoma of the Larynx, Stage IV Verrucous Carcinoma of the Oral Cavity, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase 1 Study of Vorinostat in Combination With Paclitaxel and Carboplatin in Solid Tumors (With Focus on Upper Aerodigestive Cancers) in Persons With HIV Infection


PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of vorinostat in combination with paclitaxel and
carboplatin in patients with solid tumors and HIV infection.

II. Determine the maximum-tolerated dose (MTD) of this combination in this patient
population.

SECONDARY OBJECTIVES:

I. Preliminarily assess response rates to this therapeutic combination in patients with
lung, head and neck, and esophageal cancers.

II. Evaluate the pathological characteristics of non-AIDS-defining cancers of the upper
aerodigestive tract.

III. Determine the presence and oncogenic activity of human papillomavirus (HPV) infection
in tumor tissue and to correlate HPV infection with clinical outcomes.

IV. Investigate the effects of vorinostat with chemotherapy on patient immune status, HIV
viral load, and latent viral reservoirs in memory T cells using highly sensitive assays.

V. Investigate possible pharmacokinetic interactions between paclitaxel and antiretroviral
therapy in persons with HIV infection.

VI. Investigate possible pharmacokinetic interactions between ritonavir and vorinostat in
patients with HIV infection.

OUTLINE: This is a multicenter, dose-escalation study of vorinostat followed by an expansion
cohort study. Patients are stratified according to highly active antiretroviral therapy
(HAART) (ritonavir-based HAART vs other or no HAART vs efavirenz-based HAART [expansion
cohort]).

Patients receive oral vorinostat once daily on days 1-5 and paclitaxel IV over 3 hours and
carboplatin IV over 30 minutes on day 3. Treatment repeats every 21 days for up to 6 courses
in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during course 1
for pharmacokinetic studies and HIV viral load analysis.

After completion of study therapy, patients are followed up every 6 months for up to 3
years.


Inclusion Criteria:



- Histologically confirmed solid malignancy meeting 1 of the following criteria:

- Non-small cell lung cancer

- Head and neck squamous cell carcinoma

- Non-gastroesophageal junction esophageal cancer

- Solid tumor that is sensitive to carboplatin and/or taxanes including, but not
limited to, any of the following (dose-escalation phase only):

- Salivary gland cancer

- Gastric cancer

- Breast cancer

- Ovarian cancer

- Anal cancer

- No Kaposi sarcoma

- Metastatic or unresectable disease and considered incurable

- Known HIV infection by ELISA, positive western blot, or any other federally approved
(licensed) HIV test

- Measurable disease

- At least 1 measurable tumor

- No known brain metastases

- Hormone receptor status not specified

- Menopausal status not specified

- ECOG performance status (PS) 0-2 (Karnofsky PS 50-100%)

- Life expectancy > 12 months

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 50 mL/min

- Serum magnesium normal

- Serum potassium normal

- CD4 count > 150/mm³ within the past 2 weeks

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use adequate contraception (hormonal or barrier method of birth
control, or abstinence) prior to, during, and for ≥ 3 months after study completion

- Must be capable of complying with study protocol

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to vorinostat or other agents used in study (including
hypersensitivity to paclitaxel, Cremophor, or platinum-based therapy)

- Able to take oral medication (vorinostat tablets must be swallowed whole)

- No peripheral neuropathy > grade 1

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Opportunistic infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- Recovered to ≤ grade 1 toxicities

- No more than 1 prior systemic therapy for palliative treatment of metastatic or
unresectable relapsed disease

- At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas
or mitomycin C) given with curative intent

- Prior taxane, including paclitaxel or docetaxel, and/or platinum exposure allowed
provided patients did not experience disease progression within 3 months after the
platinum-based therapy

- Any prior or concurrent antiretroviral therapy allowed provided patient has been on a
stable regimen for ≥ 4 weeks with no intention to change the regimen within 8 weeks
after study entry

- No concurrent zidovudine or stavudine

- No prior vorinostat or other known HDAC inhibitors as cancer therapy

- At least 2 weeks since prior valproic acid

- No other concurrent investigational agents

- No concurrent ketoconazole

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum-tolerated dose of vorinostat in combination with paclitaxel and carboplatin determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Missak Haigentz

Investigator Role:

Principal Investigator

Investigator Affiliation:

AIDS Associated Malignancies Clinical Trials Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02511

NCT ID:

NCT01249443

Start Date:

August 2011

Completion Date:

Related Keywords:

  • HIV Infection
  • Recurrent Anal Cancer
  • Recurrent Breast Cancer
  • Recurrent Esophageal Cancer
  • Recurrent Gastric Cancer
  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Non-Small Cell Lung Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Salivary Gland Cancer
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Verrucous Carcinoma of the Larynx
  • Recurrent Verrucous Carcinoma of the Oral Cavity
  • Salivary Gland Squamous Cell Carcinoma
  • Stage IV Anal Cancer
  • Stage IV Breast Cancer
  • Stage IV Esophageal Cancer
  • Stage IV Gastric Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Stage IV Salivary Gland Cancer
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Larynx
  • Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IV Squamous Cell Carcinoma of the Oropharynx
  • Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IV Verrucous Carcinoma of the Larynx
  • Stage IV Verrucous Carcinoma of the Oral Cavity
  • Unspecified Adult Solid Tumor, Protocol Specific
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Anus Neoplasms
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Squamous Cell
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Laryngeal Diseases
  • Lung Neoplasms
  • Stomach Neoplasms
  • Carcinoma, Verrucous
  • Head and Neck Neoplasms
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

Montefiore Medical CenterBronx, New York  10467-2490
Pennsylvania Oncology Hematology AssociatesPhiladelphia, Pennsylvania  19107
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
AIDS - Associated Malignancies Clinical Trials ConsortiumRockville, Maryland  20850