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

Dose escalation:
To determine the recommended maximal tolerated dose (MTD) or recommended phase II dose of single agent ONC201 orally once every three weeks

Dose expansion:
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).
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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.
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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.
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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.
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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.
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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.
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Response and Safety of Cetuximab Administration as First Line Therapy in Patients with Unresectable Squamous Cell Skin Carcinoma: A Retrospective Chart Review

To document the cetuximab experience in this patient population which represents an unmet need and use this information as a reference point to begin to design future studies.
-to describe that cetuximab with or without chemotherapy is well tolerated among patients with advanced and unresectable squamous cell carcinoma and will show preliminary efficacy that should be explored in future, randomized studies.
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NCI/CTEP #8983: A Phase I Trial of MK-2206 and Hydroxychloroquine in Solid Tumors, Melanoma, Renal and Prostate Cancer to Examine the Role of Autophagy in Tumorigenesis

Primary - to define the maximum tolerated dose (MTD) of MK-2206 and hydroxychloroquine (HCQ) when used in combination.
Secondary - (1) to determine the side effects and activity of MK-2206 and hydroxychloroquine when used in combination. (2) to determine if hydroychloroquine alters the pharmcokinetics of MK-2206 due to a drug-drug interaction. (3) to validate biomarkers for autophagy detection
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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
of POL-103A.
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
Secondary Objectives
2.2 2.2.1
2.2.2
␣ To verify the safety and tolerability of POL-103A at the dose selected for Part B.
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ECOG E2810: Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients with Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy

1 .To evaluate disease-free survival with pazopanib as compared to placebo, defined as the time from randomization to the development of recurrent disease, second primary cancer (other than localized breast, localized prostate, or non-melanoma skin cancer) or death from any cause for patients with metastatic RCC with no evidence of disease following metastatectomy.
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ECOG E3611, A Randomized Phase II Study of Ipilimumab at 3mg/kg or 10mg/kg Alone or in Combination with High Dose Interferon-alpha in Advanced Melanoma

The purpose of this study is to compare the effects, good and/or bad, of ipilimumab (given at 2 different doses, 10 mg/kg or 3 mg/kg) either alone or in combination with interferon alfa-2b on you and your melanoma to find out which treatment is safer and better. Therefore, you will get ipilimumab (either at 10 mg/kg or 3 mg/kg) alone or in combination with interferon alfa-2b.
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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.
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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 Previously Untreated, Unresectable, 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.
Secondary Objective(s):
Phase 1b:
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
Phase 2:
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
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A safety study for MSB0010445 in combination with Stereotactic Body Radiation in advanced melanoma subjects following prior treatment with ipilimumab

The primary objective of the trial is as follows:
- To determine the maximum tolerated dose (MTD) of MSB0010445 in combination with Stereotactic Body Radiation Therapy (SBRT) in subjects with advanced melanoma
The exploratory objectives of the trial are as follows:
- To establish that MSB0010445 in combination with SBRT is clinically active through the observation of best overall response assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
- To further characterize the safety of MSB0010445 in combination with SBRT
- To characterize the immunogenicity of MSB0010445
- To characterize the pharmacokinetics (PK) of MSB0010445
- To propose that MSB0010445 in combination with SBRT is biologically active by observing modifications of the tumor microenvironment (by infiltration of CD8+ T cells and of regulatory T cell [Treg] in the tumor)
- To evaluate potential biomarkers of immune response correlated with clinical activity by analysis of tumor and peripheral blood samples
- To establish that MSB0010445 is clinically active through the observation of best overall response assessed by modified immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
- To evaluate the pharmacodynamic activity of MSB0010445 in combination with radiotherapy in peripheral blood
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EMR 100070-003: A Phase 2, open-label, multicenter trial to investigate the clinical activity and safety of MSB0010718C in subjects with Merkel cell carcinoma

The primary objective of the trial is to assess the clinical activity of MSB0010718C in subjects with metastatic Merkel cell carcinoma (MCC) as determined by the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by an Independent Endpoint Review Committee (IERC).

Secondary objectives are as follows:
To assess the duration of response according to RECIST 1.1
To assess the progression-free survival time (PFS) according to RECIST 1.1
To assess the safety profile of MSB0010718C in subjects with MCC
To assess the overall survival (OS) time

Exploratory objectives are as follows:
To characterize the pharmacokinetic (PK) profile of MSB0010718C
To evaluate the immunogenicity of MSB0010718C and to correlate it to exposure and biological activity
To assess the immune-related best overall response (irBOR) and immune-related PFS (irPFS) using the modified immune-related response criteria (irRC), derived from RECIST 1.1
To evaluate changes in biomarkers in relation to disease responses to MSB0010718C
To evaluate the association between tumor programmed death ligand 1 (PD-L1) expression and best overall response (BOR)
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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

Primary
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.

Secondary
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
oral mucosa

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.

Exploratory
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
laherparepvec.
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Web Intervention for Skin Examination and Sun-safety: Project WISESun

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.
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Proleukin® Observational Registry to Evaluate the Treatment Patterns and Clinical Response in Malignancy

Primary Objective
To establish an observational data to report and query on
Patient care patterns
* Clinical outcomes and trends from HD IL-2 therapy
in treating patients with mM, mRCC or other malignancies
Secondary Objectives
To evaluate patient/site specific prognostics and treatment emergent
outcomes associated with HD IL-2
To publish real-world practices of IL-2 immunotherapy on annual basis
To maintain an expandable database platform for future research interest
and projects relevant to IL-2 in mM and mRCC or other malignancies
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