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Participant characteristics and clinical trial decision-making factors in AIDS malignancy consortium treatment trials for HIV-infected persons with cancer (AMC #S006).

ABSTRACT: BACKGROUND:Overall, people living with HIV/AIDS (PLWHA) are living longer, but compared with the general population, they are at elevated risk for numerous AIDS-defining and non-AIDS-defining cancers. The AIDS Malignancy Consortium (AMC) is dedicated to conducting clinical trials aimed at prevention and treatment of cancers among PLWHA. OBJECTIVE:To examine patient-level characteristics and perceptions that influence decision-making regarding AMC treatment trial participation. METHODS:PLWHA diagnosed with cancer or anal high-grade intraepithelial neoplasia who were ?18 years old and offered participation on a therapeutic AMC clinical trial were eligible. Participants completed a 17-item survey assessing sociodemographic and other factors potentially influencing decision-making regarding trial participation. RESULTS:The sample of 67 participants was mainly male (n?=?62, 92.5%), non-Hispanic (89.5%) and white (67.2%), with a mean age of 48.3 years. About half of participants were screened for lymphoma studies. Nearly all (98.5%) of the participants learned about AMC clinical trials from a medical provider, most (73.1%) knew little about clinical trials in general, and half decided on trial participation on their own. Altruism was the most frequently cited reason for trial participation. Participant recommendations for improving AMC trial accrual included systems changes to speed access to clinical trials and reduce participant burden. CONCLUSIONS:This formative study highlights the perceived benefits to others, i.e. altruism, as an important factor in trial decision-making, little knowledge about clinical trials in general, and the role of physicians in informing participants about clinical trials. Future research should address knowledge barriers and explore systems- and provider-level factors affecting accrual to AMC trials.

SUBMITTER: Burkhalter JE

PROVIDER: S-EPMC6428211 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Participant characteristics and clinical trial decision-making factors in AIDS malignancy consortium treatment trials for HIV-infected persons with cancer (AMC #S006).

Burkhalter Jack E JE Aboulafia David M DM Botello-Harbaum Maria M Lee Jeannette Y JY

HIV clinical trials 20181201 6

<h4>Background</h4>Overall, people living with HIV/AIDS (PLWHA) are living longer, but compared with the general population, they are at elevated risk for numerous AIDS-defining and non-AIDS-defining cancers. The AIDS Malignancy Consortium (AMC) is dedicated to conducting clinical trials aimed at prevention and treatment of cancers among PLWHA.<h4>Objective</h4>To examine patient-level characteristics and perceptions that influence decision-making regarding AMC treatment trial participation.<h4> ...[more]

PMID: 30890062

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Project description:The purpose of this article is to describe lessons from the first lymphoma clinical trial conducted by the AIDS Malignancy Consortium (AMC) in sub-Saharan Africa (SSA). AMC-068 was a randomized phase II comparison of intravenous versus oral chemotherapy for HIV-positive diffuse large B-cell lymphoma. Opening in 2016, AMC-068 planned to enroll 90 patients (45 per arm) in Kenya, Malawi, Uganda, and Zimbabwe over 24 months and follow patients for 24 months to assess overall survival. In 2018, the study closed after screening 42 patients but enrolling only 7. Challenges occurred during protocol development, pre-activation, and postactivation. During protocol development (2011-2012), major obstacles were limited baseline data to inform study design; lack of consensus among investigators and approving bodies regarding appropriateness of the oral regimen and need for randomized comparison with cyclophosphamide, doxorubicin, vincristine, and prednisone; and heterogeneity across sites in local standards for diagnosis, staging, and treatment. During pre-activation (2012-2016), challenges included unexpected length and layers of regulatory approval across multiple countries, need to upgrade pathology capacity at sites, need to augment existing chemotherapy infusion capacity at sites, and procurement issues for drugs and supplies. Finally, during postactivation (2016-2018), challenges included long delays between symptom onset and screening entry for many patients, leading to compromised performance status and organ function; other patient characteristics that frequently led to exclusion, including high tumor proliferative index or other pathologic features that were disallowed; and costs of routine diagnostic procedures often being borne by patients, which also contributed to pre-enrollment delays. Lessons from AMC-068 are being applied to the design and conduct of new AMC lymphoma trials in SSA, and the study has contributed to a strong operational foundation that will support innovative clinical trials in the future.

Project description:BackgroundThe treatment of non-acquired immunodeficiency syndrome-defining cancers may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium to assess targeted therapies and HAART in human immunodeficiency virus-positive patients (ClinicalTrials.gov identifier: NCT00890747).MethodsIn a modified phase 1 study of sunitinib, patients were stratified into 2 treatment arms based on whether they were receiving therapy with ritonavir, a potent CYP3A4 inhibitor. Patients in treatment arm 1 (non-ritonavir HAART) received standard sunitinib dosing (50 mg/day). Treatment arm 2 (ritonavir-based HAART) used a phase 1, 3 + 3 dose escalation design (from 25 mg/day to 50 mg/day). Cycles were comprised of 4 weeks on treatment followed by a 2-week break (6 weeks total). The pharmacokinetics of sunitinib and its active metabolite (N-desethyl sunitinib) were assessed.ResultsNineteen patients were enrolled and were evaluable. Patients on treatment arm 1 tolerated treatment with no dose-limiting toxicity observed. In treatment arm 2, a dose-limiting toxicity was experienced at a dose of 37.5 mg, and an additional 3 of 5 patients experienced grade 3 neutropenia (toxicity graded as per National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]), an uncommon toxicity of sunitinib. No patient achieved a response, but 10 patients had stable disease, including 8 with prolonged disease stability. Efavirenz, a potent inducer of CYP3A4, resulted in increased exposure of N-desethyl sunitinib, whereas ritonavir caused decreased exposure of the metabolite. Hand-foot syndrome was associated with higher steady-state trough concentrations of sunitinib.ConclusionsPatients receiving non-ritonavir-based HAART regimens tolerated standard dosing of sunitinib. Patients receiving ritonavir-based therapy who were treated with a dose of 37.5 mg/day experienced higher toxicities. Dose reductions of sunitinib to 37.5 mg may be warranted in patients receiving ritonavir.

Project description:Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity.The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV-associated NHL who received either R-CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R-EPOCH (n = 51; AMC034). Age-adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (<100/?L vs ?100/?L), and treatment (R-CHOP vs R-EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in a Cox proportional hazards regression models for event-free survival (EFS) and overall survival (OS).Features that were associated significantly with an improved CR rate and improved EFS and OS included a low aaIPI score and a baseline CD4 count ?100/?L. When the analysis was adjusted for aaIPI and CD4 count, patients who received concurrent R-EPOCH had improved EFS (hazard ratio [HR] 0.40; 95% confidence intervals [CI], 0.23, 0.69; P < .001) and OS (HR, 0.38; 95% CI, 0.21, 0.69; P < .01). Treatment-associated death occurred significantly more often in patients with CD4 counts <50/?L (37% vs 6%; P < .01).The current analysis provided additional level 2 evidence supporting the use of concurrent R-EPOCH in patients with HIV-associated lymphoma and a CD4 count >50/?L, and the results support the design of an ongoing phase 3 trial comparing concurrent R-EPOCH with R-CHOP in immunocompetent patients with diffuse large B-cell lymphoma (National Clinical Trial no. NCT00118209).

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Participant characteristics and clinical trial decision-making factors in AIDS malignancy consortium treatment trials for HIV-infected persons with cancer (AMC #S006).

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Participant characteristics and clinical trial decision-making factors in AIDS malignancy consortium treatment trials for HIV-infected persons with cancer (AMC #S006).

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