Trial record 8 of 19 for:    Open Studies | "Paranasal Sinus Neoplasms"

Vorinostat in Combination With Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01249443
First received: November 25, 2010
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

This phase I clinical trial is studying the side effects and the best dose of vorinostat when given together with paclitaxel and carboplatin in treating patients with metastatic or recurrent solid tumors and human immunodeficiency virus (HIV) infection. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with paclitaxel and carboplatin may kill more tumor cells.


Condition Intervention Phase
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
Drug: vorinostat
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
Drug: carboplatin
Drug: paclitaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of adverse events during paclitaxel and carboplatin treatment according to dose-limiting toxicities (DLTs), graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rates in patients with lung, head and neck, and esophageal cancers assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    For each stratum, binomial proportions and their 95% confidence intervals will be used to preliminarily assess response rates of the therapeutic combination in lung, head and neck, and esophageal cancers.

  • Effects of therapy on HIV viral load and CD4 cell count [ Time Frame: Baseline and at 6, 12, and 18 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: November 2013
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat, carboplatin, paclitaxel)
Patients receive vorinostat PO 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.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: diagnostic laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of vorinostat in combination with paclitaxel and carboplatin in solid tumor patients with HIV infection.

II. To determine the maximal tolerated dose (MTD) of the combination in this patient population.

*NOTE: An administrative decision was made by Cancer Therapy Evaluation Program (CTEP) to halt further study of vorinostat in this specific patient population as of February 1, 2013, and no patients remain on vorinostat. The primary objective going forward will determine the safety and tolerability of the paclitaxel and carboplatin combination in this patient population.

SECONDARY OBJECTIVES:

I. To preliminarily assess response rates of the therapeutic combination in lung, head and neck, and esophageal cancers.

II. To evaluate the pathological characteristics of non-acquired immunodeficiency syndrome (AIDS) defining cancers of the upper aerodigestive tract.

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

IV. To investigate possible pharmacokinetic interactions between paclitaxel and antiretroviral therapy in persons with HIV infection.

OUTLINE: This is a multicenter, dose-escalation study of vorinostat followed by an expansion cohort study.

Patients receive vorinostat orally (PO) once daily on days 1-5 and paclitaxel intravenously (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.

Note: An administrative decision was made by CTEP to halt further study of vorinostat in this specific patient population as of February 1, 2013. No patients remain on vorinostat. The primary objective going forward will determine the safety and tolerability of the paclitaxel and carboplatin combination in this patient population, without vorinostat. The information pertaining to vorinostat is for historical purposes.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have known HIV infection and histologically confirmed solid malignancy that is metastatic or unresectable and is therefore incurable; although the focus of this trial will be on upper aerodigestive cancers (non-small cell lung cancer, head and neck squamous cell carcinoma, and non-gastroesophageal junction esophageal cancer), patients with other incurable solid tumor with disease potentially sensitive to carboplatin and/or taxanes (including but not limited to salivary gland cancer, gastric cancer, breast cancer, ovarian cancer, or anal cancer, BUT excluding Kaposi sarcoma), will be eligible
  • Up to 1 prior systemic therapy regimen will be permitted for palliative treatment of metastatic or unresectable relapsed disease; however, previous chemotherapy delivered with curative-intent (i.e., chemoradiotherapy or adjuvant [postoperative] chemotherapy at a time disease was considered potentially curable) will be permitted; prior taxane (including paclitaxel or docetaxel) and/or platinum exposure will be permitted; however, patients must not experience disease progression within 3 months of platinum-based therapy; at least 4 weeks must have elapsed since prior chemotherapy or radiation therapy, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C; toxicities from prior anticancer therapy must have recovered to =< Grade 1
  • Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive Western Blot, or any other federally approved licensed HIV test; a positive HIV viral load prior to study entry will also be permitted
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
  • Documented life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Additionally, serum magnesium and potassium must be within institutional normal limits, and a CD4 count > 100/mcL will be required within 2 weeks of study participation
  • Presence of at least one measureable tumor lesion is required
  • Participating patients must receive medically appropriate care and treatment for HIV infection, including antiretroviral medications, when clinically indicated, and should be under the care of a physician experienced in HIV management; with the exception of treatment with zidovudine and stavudine, patients will be eligible regardless of antiretroviral regimen (no antiretroviral therapy, nonnucleoside reverse transcriptase inhibitors [NNRTI]-based therapy, or protease inhibitor based therapy), provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 8 weeks following study entry; the exact regimen used for HIV therapy will be captured on Case Report Forms; as study-specific (antiretroviral therapy-based) strata fill, however, only patients fitting the remaining open strata will be accrued
  • Because histone deacetylase inhibitors as well as other therapeutic agents used in this trial 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, during the duration of study participation, and for at least 3 months following study completion; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; women of child-bearing potential must have a negative pregnancy test within 7 days before initiation of study drug dosing; post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; (Note: A woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)
  • Ability to understand and the willingness to sign a written informed consent document; as the correlative studies are critical to the clinical and scientific value of the trial, CD4 count/HIV viral load determinations will be required, and participation in the tumor-based correlative studies will be strongly recommended; additionally, investigators MUST request sample donation to the AIDS Cancer Specimen Resource (ACSR); however, the patient may refuse sample donation; patients accrued to the expansion phase of the study will be required to undergo pharmacokinetic sampling
  • Subjects must in the opinion of the Investigator be capable of complying with this protocol

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 (toxicities not improved to =< Grade 1) due to agents administered more than 4 weeks earlier; additionally, patients experiencing disease progression within 3 months of platinum-based therapy will be excluded from trial participation
  • Due to availability of effective first- and second-line therapies (as well as disease-specific clinical trials), patients with diagnosis of active Kaposi sarcoma will be excluded from study participation; however, persons with other active malignancy with prior history of Kaposi sarcoma can be considered for participation at the discretion of the Study Chair
  • Patients may not be receiving any other investigational agents
  • Patients with known 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents used in study (including hypersensitivity to paclitaxel, Cremophor, or platins)
  • For subjects assigned to take vorinostat, inability to take oral medications; vorinostat capsules must be administered whole; note: this criterion does NOT apply to subjects treated on the Expansion Cohort (accruals post February 1, 2013)
  • As ketoconazole may inhibit paclitaxel metabolism, patients receiving ketoconazole for any treatment indication are ineligible; patients receiving any other medications or substances that are inhibitors or inducers of CYP450 enzymes will be eligible; however, use all such medications or substances must be documented in the Case Report Forms
  • For subjects assigned to take vorinostat, prior exposure to vorinostat or other known histone deacetylase (HDAC) inhibitors for cancer therapy; patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to study enrollment; note: this criterion does NOT apply to subjects treated on the Expansion Cohort (accruals post February 1, 2013)
  • Since zidovudine and stavudine have potential for severe hematological toxicity potentially overlapping with toxicities of the study therapy, treatment with these agents will be disallowed
  • Due to potential toxicity associated with study therapy (particularly with paclitaxel), patients with peripheral neuropathy > Grade 1 will be excluded from study participation
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, opportunistic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with HIV infection will be eligible provided they meet the criteria specified; patients with known Hepatitis B infection should be screened for active disease prior to study participation; patients with chronic Hepatitis C infection will be eligible at the discretion of the treating investigator
  • Pregnant women are excluded from this study and women who become pregnant while on study must be immediately discontinued; women who are breastfeeding will not be eligible for study participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01249443

Locations
United States, California
UC San Diego Moores Cancer Center Recruiting
LA Jolla, California, United States, 92093
Contact: William Wachsman    858-552-8585ext2628    wwachsman@ucsd.edu   
Principal Investigator: William Wachsman         
UCLA Center for Clinical AIDS Research and Education Recruiting
Los Angeles, California, United States, 90035
Contact: Ronald T. Mitsuyasu    888-798-0719    rmitsuya@mednet.ucla.edu   
Principal Investigator: Ronald T. Mitsuyasu         
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Recruiting
Washington, District of Columbia, United States, 20057
Contact: Missak Haigentz    718-920-4826    mhaigent@montefiore.org   
Principal Investigator: Missak Haigentz         
United States, Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Juan C. Ramos    000-000-0000ext0      
Principal Investigator: Juan C. Ramos         
United States, Maryland
AIDS - Associated Malignancies Clinical Trials Consortium Recruiting
Rockville, Maryland, United States, 20850
Contact: Missak Haigentz    718-920-4826    mhaigent@montefiore.org   
Principal Investigator: Missak Haigentz         
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Timothy P. Cooley    617-638-8265    timothy.cooley@bmc.org   
Principal Investigator: Timothy P. Cooley         
United States, Missouri
Siteman Cancer Center at Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Lee Ratner    800-600-3606    info@siteman.wustl.edu   
Principal Investigator: Lee Ratner         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467-2490
Contact: Ronald T. Mitsuyasu    301-557-1891    rmitsuya@mednet.ucla.edu   
Principal Investigator: Missak Haigentz         
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates Recruiting
Philadelphia, Pennsylvania, United States, 19106
Contact: David H. Henry    215-829-6088    davidhenry@pennoncology.com   
Principal Investigator: David H. Henry         
United States, Washington
Benaroya Research Institute at Virginia Mason Recruiting
Seattle, Washington, United States, 98101-2795
Contact: David M. Aboulafia    800-354-9527    david.aboulafia@vmmc.org   
Principal Investigator: David M. Aboulafia         
Sponsors and Collaborators
Investigators
Principal Investigator: Missak Haigentz AIDS Associated Malignancies Clinical Trials Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01249443     History of Changes
Other Study ID Numbers: NCI-2011-02511, NCI-2011-02511, CDR0000689900, AMC-078, AMC-078, U01CA121947
Study First Received: November 25, 2010
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Paranasal Sinus Neoplasms
Infection
Communicable Diseases
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Carcinoma, Squamous Cell
HIV Infections
Acquired Immunodeficiency Syndrome
Stomach Neoplasms
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Laryngeal Diseases
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Carcinoma, Verrucous
Breast Neoplasms
Carcinoma
Nasopharyngeal Neoplasms
Salivary Gland Neoplasms
Anus Neoplasms
Head and Neck Neoplasms
Neoplasms, Unknown Primary
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic

ClinicalTrials.gov processed this record on October 01, 2014