A Phase 1 Study of Paclitaxel and Carboplatin in Solid Tumors (With Focus on Upper Aerodigestive Cancers) in Persons With HIV Infection
Overview
- Phase
- Phase 1
- Intervention
- vorinostat
- Conditions
- HIV Infection
- Sponsor
- AIDS Malignancy Consortium
- Enrollment
- 17
- Locations
- 10
- Primary Endpoint
- 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)
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
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
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
Arms & Interventions
Treatment (carboplatin, paclitaxel)
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.
Intervention: vorinostat
Treatment (carboplatin, paclitaxel)
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.
Intervention: diagnostic laboratory biomarker analysis
Treatment (carboplatin, paclitaxel)
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.
Intervention: pharmacological study
Treatment (carboplatin, paclitaxel)
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.
Intervention: carboplatin
Treatment (carboplatin, paclitaxel)
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.
Intervention: paclitaxel
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)