Brief Title
Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection
Official Title
A Phase 1 Study of Paclitaxel and Carboplatin in Solid Tumors (With Focus on Upper Aerodigestive Cancers) in Persons With HIV Infection
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.
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
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)
Secondary Outcome
Response rates in patients with lung, head and neck, and esophageal cancers assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1
Condition
HIV Infection
Intervention
vorinostat
Study Arms / Comparison Groups
Treatment (carboplatin, paclitaxel)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
17
Start Date
November 2013
Completion Date
December 2017
Primary Completion Date
May 2016
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Missak Haigentz, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01249443
Organization ID
AMC-078
Secondary IDs
NCI-2011-02511
Responsible Party
Sponsor
Study Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Missak Haigentz, Principal Investigator, AIDS Associated Malignancies Clinical Trials Consortium
Verification Date
July 2020