|Protocol||Trial Name and Objective|
A first-in-human phase I single-agent open-label dose-escalation study of every three-week dosing of oral ONC201 in patients with advanced solid tumors
To determine the recommended maximal tolerated dose (MTD) or recommended phase II dose of single agent ONC201 orally once every three weeks
To characterize the safety and tolerability of ONC201 in patients with tumors that have a high frequency of PI3 kinase pathway or RAS signaling activation (metastatic castrate resistant prostate cancer, metastatic renal cell carcinoma, melanoma, glioblastoma multiforme, breast cancer).
A Media Literacy Indoor Tanning Program
This project consists of the development and pilot testing of a novel intervention designed to reduce indoor artificial ultraviolet tanning bed (IT) use among young women.
Skin Cancer Prevention, Risk, and Surveillance Behaviors among Puerto Rican Adults
The increasing incidence of skin cancer in Puerto Rico in recent years has not been accompanied by heightened research or public health initiatives. We will address this issue in the current project by developing and implementing a comprehensive, theory-driven, culturally relevant survey of skin cancer-related behaviors and potential correlates in a representative sample of adults in Puerto Rico. The knowledge gained from this project will directly inform the development of an intervention to promote skin cancer prevention and surveillance behaviors among Puerto Rican adults.
A Tailored Internet Intervention for Skin Cancer Risk Reduction in Young Adults
The purpose is to test a tailored intervention delivered via the Internet designed to reduce skin cancer risk behavior among young adults at moderate to high risk of developing skin cancer. The tailored intervention will feature individually tailored messages as well as multimedia & interactive material. The tailored intervention will emphasize appearance concerns, which are known to be the primary motivation for UV exposure & lack of skin protection among young adults. This will be accomplished in part through the use of personalized facial images showing UV damage as well as computerized age progression demonstrations. Additional variables that will be tailored upon will be drawn from our guiding theoretical model,Fishbein's Integrative Model,16 & have been found to be associated with UV-related behavior in the literature & our own work. These variables are demographic variables, appearance consciousness,past UV-related behavior,UV-related knowledge, beliefs,norms,self-efficacy,& intentions. However,more research is needed on mechanisms of skin cancer risk behavior change.
Aim 1.To examine the efficacy of a tailored intervention delivered via the Internet designed to increase skin protection & decrease sun exposure behavior among young adults at moderate to high risk of developing skin cancer. Participants will be randomized to the tailored intervention,the Skin Cancer Foundation website,or an assessment only condition.
Aim 2.To evaluate whether socio-demographic variables (sex,race/ethnicity, skin type,family history of skin cancer,education,socioeconomic status,& geographic locale),appearance consciousness,& past exposure & protective behaviors moderate intervention effects.
Aim 3.To evaluate whether Integrative Model 16 constructs (UV-related knowledge, risk perception,beliefs,norms,self-efficacy,& intentions) mediate intervention effects.These mediators & the behavioral outcomes will be assessed at baseline as well as 3 weeks & 3 months post baseline.
Sun Protection and Skin Surveillance: Beliefs and Behaviors of Childhood Cancer Survivors
To establish the prevalence and correlates of skin cancer prevention and surveillance behaviors among CCS using depth interviews and survey research.
Tailored Intervention for Melanoma Patients' Families
The primary aim is to evaluate the impact of an enhanced tailored internet intervention (Skin TII) versus the previously evaluated tailored print and phone counseling (TPC) on the engagement in TCE, the thoroughness of SSE, and the sun protection habits of FDRs at increased risk for melanoma.
The secondary aim is to determine whether behavioral intentions, SSE self-efficacy, and sunscreen self-efficacy mediate the expected association between the interventions and TCE, SSE thoroughness, and sun protection, with stronger effects for Skin TII. We do not expect benefits and barriers to mediate treatment effects, but we will explore these as possible mediators in our analyses.
The exploratory aim is to evaluate whether user characteristics (Internet usage, internet experience, learning style, internet self-efficacy) and health care access (insurance status, distance from a dermatologist) moderate the expected associations between the Skin TII and outcomes and evaluate the perception, perceived impact, usability, and barriers of use of the Skin TII intervention. We will also evaluate the cost effectiveness of each intervention.
The Development and Evaluation of a Behavioral Intervention to Reduce Indoor Tanning
1.1 Primary Objective
Phase 1a-c: To use a series of three qualitative research studies to inform the development of an indoor tanning intervention.
Phase 2: To develop and evaluate an online tailored IT intervention based on findings from Phase 1.
1.2 Specific Aims
Aim 1 (Phase 1a): To use key informant interviews to produce an ethnographic description of the IT culture and associated language and concepts based on key informant interviews with IT users.
Aim 2 (Phase 1b): To use long interviews with IT users in order to examine the importance of the proposed SRT constructs.
Aim 3 (Phase 1c): To use focus groups to explore a range of experiences related to the SRT constructs among IT users as well as differences in perceptions of these factors.
Aim 4 (Phase 2): To determine if the intervention is feasible and acceptable to participants.
Aim 5 (Phase 2): To analyze preliminary outcome data in terms of the effectiveness of the intervention in reducing IT behaviors among participants compared to control participants.
A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects with Melanoma Metastatic to the Brain treated with Nivolumab in Combination with Ipilimumab followed by Nivolumab Monotherapy
Primary Objective: To assess the CNS clinical benefit rate (CBR, defined as CR + PR + SD > 6 months per protocol-defined response criteria) in subjects with malignant melanoma metastatic to the brain treated with nivolumab combined with ipilimumab followed by nivolumab monotherapy.
A Multicenter, Double-blind, Placebo-controlled, Adaptive Phase 3 Trial of POL-103A Polyvalent Melanoma Vaccine in Post-resection Melanoma Patients with a High Risk of Recurrence
Part A Objectives
␣ To evaluate the safety of POL-103A in patients with stage IIB, IIC, or III melanoma. ␣ To evaluate the biological activity of POL-103A in patients with stage IIB, IIC, or III
melanoma. ␣ To select the dose for Part B. ␣ To collect blood samples for the future investigation of the sustained biologic activity
Part B Objectives Primary Objective
␣ To assess the efficacy of treatment with POL-103A compared to placebo with respect to recurrence-free survival or overall survival
␣ To verify the safety and tolerability of POL-103A at the dose selected for Part B.
NCI/CTEP# 9466: Phase I/II study of dabrafenib, trametinib, and navitoclax in BRAF mutant melanoma and other solid tumors
1.1 Phase I Objectives
1.1.1 Primary Objective
18.104.22.168 To determine the maximum tolerate dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors.
1.1.2 Secondary Objectives
22.214.171.124 To describe pharmacodynamics effects of treatment with dabrafenib, trametinib, and navitocalx on both serial tumor biopsies and serial blood draws in a small subset of patients treated with BRAF-mutant melanoma.
126.96.36.199 To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax.
1.2 Phase II Objectives
1.2.1 Primary Objectives
188.8.131.52 To estimate the complete response (CR) rate in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, and navitoclax as compared to the historical control.
184.108.40.206 To compare the maximal tumor regression in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax.
1.2.2 Secondary Objectives
220.127.116.11 To compare the PFS, OS, and ORR in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax.
18.104.22.168 To compare the degree of apoptosis induced in on-treatment biopsies of patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax.
22.214.171.124 To explore other pharmacodynamic effects in on-treatment biopsies of patients with BRAF-mutant melanoma treated with either dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax including cell proliferation (Ki-67), proteomics (RPPA), and BCL-2 family gene expression analysis.
A Phase II Single Arm Study of High-Dose IL-2 and Ipilimumab in Patients with Unresectable Stage III and Stage IV Melanoma
1.The combination of Ipilimumab and high-dose IL-2 improves clinical responses.
2.The combination of Ipilimumab and high-dose IL-2 is feasible and has an acceptable safety profile.
3.The combination of Ipilimumab and high-dose IL-2 results in increased effector CD8+ T cells and decreased CD4+FoxP3+ regulatory T cells in responding patients.
A Phase 1b/2, Multicenter, Open-label Trial to Evaluate the Safety and
Efficacy of Talimogene Laherparepvec and Ipilimumab Compared to Ipilimumab
Alone in Subjects With Unresected, Stage IIIB-IV Melanoma
Phase 1b: To determine the safety and tolerability of talimogene laherparepvec in combination with ipilimumab as assessed by incidence of dose-limiting toxicities (DLT) in subjects with previously untreated, unresectable, stages IIIb to IV melanoma.
Phase 2: To estimate the efficacy of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone as assessed by overall survival (OS) in subjects with previously untreated, unresectable, stages IIIb to IV melanoma.
To estimate the efficacy of talimogene laherparepvec in combination with ipilimumab as
determined by objective response rate (ORR)
To assess the safety of talimogene laherparepvec in combination with ipilimumab as determined by incidence of all adverse event (AE)s, grade ? 3 AEs (AEs), serious adverse events (SAEs), and events requiring the discontinuation of study drug, local effects on the tumor (ie, pain, inflammation and ulceration), clinically significant laboratory changes, and clinically significant changes in vital signs not defined as DLT
To estimate the efficacy of talimogene laherparepvec in combination with ipilimumab versus
ipilimumab alone as determined by ORR, duration of response (DOR), time to response (TTR), progression free survival (PFS), resection rate, 1-year survival rate, and 2-year survival rate
To assess the safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone as determined by incidence of all AEs, grade ? 3 AEs, SAEs, and events requiring the discontinuation of study drug, local effects on the tumor (ie, pain, inflammation and ulceration), clinically significant laboratory changes, and clinically significant changes in vital signs
A Phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical
activity of MSB0010718C in subjects with metastatic or locally advanced solid tumors and expansion to selected indications.
To assess the safety and tolerability of MSB0010718C and to determine the maximum tolerated dose (MTD) of MSB0010718C in subjects with metastatic or locally advanced solid tumors.
- To characterize the pharmacokinetic (PK) profile of MSB0010718C and to correlate exposure with target occupancy.
- To evaluate the immunogenicity of MSB0010718C and to correlate it to exposure
and biological activity.
- To assess the best overall response (BOR) andprogression-free survival time (PFS) according to Response Evaluation Criteria in Solid Tumors
- To assess the immune-related BOR (irBOR) and immune-related PFS (irPFS) using the modified Immune-Related Response Criteria (irRC),
derived from RECIST 1.1.
- To assess overall survival time (OS).
- To evaluate biological responses to MSB0010718C in blood/serum.
- To evaluate the association between tumor programmed death ligand 1 (PD-L1) expression and BOR.
20120324: A Phase 2, Multicenter, Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec in Subjects With Unresected, Stage IIIb to IVM1a Melanoma
The primary objective is to estimate the proportion of subjects with detectable
talimogene laherparepvec DNA in the blood and urine anytime after administration of talimogene laherparepvec within the first 3 cycles.
The secondary objectives are as follows:
to estimate the incidence of clearance of talimogene laherparepvec DNA from blood and urine overall and by baseline herpes simplex virus type 1 (HSV-1) serostatus(seronegative versus seropositive) during each of the first 3 cycles
to estimate the rate of detection of talimogene laherparepvec DNA and virus from
exterior of occlusive dressing and injected lesion
to estimate the rate of detection of talimogene laherparepvec DNA and virus from
to estimate the incidence of detection of talimogene laherparepvec DNA in lesions suspected to be herpetic in origin
to describe the efficacy of talimogene laherparepvec as assessed by objective
response rate (ORR) at 3, 6, 12, and 18 months, as well as by best overall response rate (BORR) achieved in subjects with unresected, stage IIIb-IVM1a melanoma
to describe the safety profile of talimogene laherparepvec in subjects with
unresected, stage IIIb-IVM1a melanoma.
The exploratory objectives are as follows:
-to assess blood and tumor for potential biomarkers (eg, proteins and [RNA
transcripts) which predict clinical outcomes to talimogene laherparepvec
-to assess fresh tumor biopsy samples for infiltrating immune cells induced by
talimogene laherparepvec and clinical response or resistance to talimogene
A Phase I Study of the Clinical and Immunologic Effects of ALT-803, a Novel Recombinant IL-15 Complex, in Patients with Advanced Melanoma
Primary Objectives: (1) to study the safety of escalating doses of ALT-803 in patients with advanced melanoma and screen the selected dose in an expansion cohort for evidence of antitumor activity. (2) to evaluate the effect of escalating doses of ALT-803 on the peripheral blood white blood cell (WBC) and absolute lymphocyte (ALC) counts.
Secondary Objectives: To evaluate the effect of escalating doses of ALT-803 on: (1) the number and phenotype of peripheral blood mononuclear cells (PBMCs), including T and natrual killer (NK) cells by multiparameter flow cytometry. (2) the level of immune response to autochthonous viral and tumor antigens by interferon-gamma ELISPOT. (3) immunogenicity and pharmacokinetics of ALT-803. (4) overall objective response rate (ORR) and response duration.
Internet Intervention for Sun Protection and Skin Self-Check Behaviors
The overall purpose of this project is to develop and test a web-based intervention to promote skin self-examination (SSE) and sun protection behaviors among individuals diagnosed with melanoma.
Individuals diagnosed with melanoma are at increased risk for second primary melanoma and disease recurrence, and it is recommended that they periodically receive a total cutaneous examination (TCE) from a physician, perform a regular SSE, and routinely engage in sun protection behaviors.1 Although patients typically have a periodic TCE, our previous research suggests that more than two-thirds of them do not perform a thorough, full-body SSE on a sufficiently regular basis.2 We have also found that many patients fail to engage in one or more sun protection behaviors.3 There is a critical need to develop effective interventions to promote SSE and sun protection behaviors among melanoma patients. In the proposed research, we will develop and test an innovative web-based intervention to promote skin surveillance and sun protection behaviors among melanoma patients.
The project will be conducted in two phases. Phase 1 focuses on intervention development, usability testing, and refinement. In Phase 2, we will conduct a randomized controlled trial (RCT) comparing the efficacy of an interactive tailored website (ITW) versus Usual Care in promoting SSE and sun protection behaviors among melanoma patients who completed surgical treatment from 3'24 months previously.
Adjuvant Treatment Patterns and Clinical Outcomes of Melanoma: A National Cancer Database Study
2.1. Primary Objectives
To examine the proportion of subjects diagnosed with AJCC stage IIB, IIC and III melanoma between 2002 and 2011 who received adjuvant immunotherapy following complete resection.
To examine patient, clinical, and disease characteristics that predict the receipt of adjuvant immunotherapy among subjects with AJCC stage IIB, IIC and III melanoma.
To examine patterns of staging procedures and initial treatment for patients diagnosed with AJCC stage II and III melanoma.
2.2. Secondary Objectives
* To examine overall survival by tumor stage (AJCC stage IIB, IIC, IIIA, IIIB and IIIC).
* To compare overall survival among patients with stage II melanoma who have documented negative nodes (through SLNB or complete lymph node dissection) with patients without confirmation of negative nodes.
Project SOL - Sun Safety for Outdoor Laborers
The goal of this project is to develop and test a culturally relevant sun safety education program for the Hispanic outdoor day laborer population who work or reside in the Greater New Brunswick (New Jersey) area. Although little is known about the incidence of skin cancer among Hispanic outdoor day laborers, ultraviolet radiation (UVR) exposure is a key risk factor for both
melanoma and non-melanoma skin cancers, and outdoor day laborers spend a large amount of their work exposed to UVR. The incidence of melanoma has steadily increased among U.S. Hispanics in recent years.