NCT01249443

Brief Summary

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. NOTE: An administrative decision was made by NCI to halt further study of vorinostat in this specific patient population as of February 1, 2013. No patients remain on vorinostat. Going forward this study will determine the safety and tolerability of the paclitaxel and carboplatin combination in this patient population.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Nov 2013

Longer than P75 for phase_1

Geographic Reach
1 country

10 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 25, 2010

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 29, 2010

Completed
2.9 years until next milestone

Study Start

First participant enrolled

November 1, 2013

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

July 29, 2020

Status Verified

July 1, 2020

Enrollment Period

2.5 years

First QC Date

November 25, 2010

Last Update Submit

July 28, 2020

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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)

    21 days

Secondary Outcomes (2)

  • Response rates in patients with lung, head and neck, and esophageal cancers assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1

    Up to 3 years

  • Effects of therapy on HIV viral load and CD4 cell count

    Baseline and at 6, 12, and 18 weeks

Study Arms (1)

Treatment (carboplatin, paclitaxel)

EXPERIMENTAL

Patients receive 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. Before February 1, 2013, patients also received vorinostat PO once daily on days 1-5 with paclitaxel and carboplatin.

Drug: vorinostatOther: diagnostic laboratory biomarker analysisOther: pharmacological studyDrug: carboplatinDrug: paclitaxel

Interventions

Given PO

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Treatment (carboplatin, paclitaxel)

Correlative studies

Treatment (carboplatin, paclitaxel)

Correlative studies

Also known as: pharmacological studies
Treatment (carboplatin, paclitaxel)

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin
Treatment (carboplatin, paclitaxel)

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol
Treatment (carboplatin, paclitaxel)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • +2 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Center for Clinical AIDS Research and Education

Los Angeles, California, 90035, United States

Location

Lombardi Comprehensive Cancer Center at Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

John H. Stroger Jr. Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101-2795, United States

Location

Related Publications (1)

  • Haigentz M, Moore P, Bimali M, Cooley T, Sparano J, Rudek M, Ratner L, Henry D, Ramos J, Deeken J, Rubinstein P, Chiao E. Safety and Tolerability of Carboplatin and Paclitaxel in Cancer Patients with HIV (AMC-078), an AIDS Malignancy Consortium (AMC) Study. Oncologist. 2022 Aug 5;27(8):623-e624. doi: 10.1093/oncolo/oyac004.

MeSH Terms

Conditions

HIV InfectionsAnus NeoplasmsBreast NeoplasmsEsophageal NeoplasmsStomach NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Ovarian EpithelialSalivary Gland NeoplasmsSquamous Cell Carcinoma of Head and Neck

Interventions

VorinostatCarboplatinPaclitaxelTaxes

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesRectal NeoplasmsColorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesAnus DiseasesRectal DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesHead and Neck NeoplasmsEsophageal DiseasesStomach DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeOvarian NeoplasmsEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsGenital Neoplasms, FemaleUrogenital NeoplasmsEndocrine System DiseasesGonadal DisordersMouth NeoplasmsMouth DiseasesStomatognathic DiseasesSalivary Gland DiseasesCarcinoma, Squamous Cell

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic AcidsCoordination ComplexesTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenesEconomicsHealth Care Economics and Organizations

Study Officials

  • Missak Haigentz

    AIDS Associated Malignancies Clinical Trials Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 25, 2010

First Posted

November 29, 2010

Study Start

November 1, 2013

Primary Completion

May 1, 2016

Study Completion

December 1, 2017

Last Updated

July 29, 2020

Record last verified: 2020-07

Locations