|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).
The BAMM Trial: BRAF, Autophagy and MEK inhibition in Metastatic Melanoma:
A Phase I/2 Trial of Dabrafenib, Trametinib and Hydroxychloroquine in Patients with Advanced BRAF Mutant Melanoma
1.1 Primary Objective
Phase 1: To determine the maximum tolerated dose (MTD) and preliminary safety of hydroxychloroquine (HCQ) when administered in conjunction with oral dabrafenib and trametinib (D+T) in patients with advanced BRAF mutant melanoma.
Phase 2: To assess the clinical efficacy of HCQ+D+T by 1 year PFS rate .
1.2 Secondary Objectives
1.2.1 To estimate the toxicity rates of oral HCQ when administered in conjunction with oral D+T.
1.2.2 To measure the response rate by RECIST criteria, and 1-year survival.
1.2.3 To determine the rate of squamous cell carcinoma of the skin, arthralgias, and pyrexia in patients treated with D+T and HCQ
1.2.4 To determine the type and frequency of ocular toxicities with this regimen
1.3 Correlative Objectives
1.3.1 To establish a population pharmacokinetic (PK) model for HCQ and its metabolites in combination with D+T
1.3.2 To use the population PK model to estimate the exposure of HCQ in individual patients
1.3.3 To compare PK parameters for HCQ and D+T in combination to data from published dabrafenib and trametinib single agent and combination studies
1.3.4 To measure the change in median number of autophagic vesicles/cell (mAV/cell) in serially collected tumor tissue with D+T alone and with D+T + HCQ and correlate these changes with HCQ exposure
1.3.5 To determine if markers of T cell immunity are increased or decreased in D+T and D+T + HCQ treated tumor compared to baseline
1.3.6 To characterize changes in gene expression within the tumor microenvironment with D+T+ HCQ treatment in patients.
1.3.7 To evaluate whether or not treatment results in modulation of systemic immunity by assessing peripheral cytokine levels
1.3.8 To determine if blood based candidate biomarkers of autophagy modulation reflect autophagy dynamics in tumors of patients
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.
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.
Sun Protection and Skin Self-Examination Among Families Coping With Early Onset Melanoma: A Pilot Study
Aim 1: To examine the level of concordance between patients with melanoma diagnosed before the age of 40 years with their family members with regard to their sun protection and skin self-examination (SSE) practices
Aim 2: To examine demographic, personal attitudes, and family values regarding skin cancer risk reduction which are associated with sun protection and SSE practices among patient and family members as well as correlates of greater concordance between patient and family members.
Aim 3: To develop a brief, easy to use web-based intervention for patients and their family members that targets sun protection and SSE practices and obtain pilot data regarding its value, use, and efficacy.
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
220.127.116.11 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
18.104.22.168 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.
22.214.171.124 To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax.
1.2 Phase II Objectives
1.2.1 Primary Objectives
126.96.36.199 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.
188.8.131.52 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
184.108.40.206 To compare the PFS, OS, and ORR in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax.
220.127.116.11 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.
18.104.22.168 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 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.
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)
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.
Phase I Study of Intratumoral CAVATAK (Coxsackievirus A21) and Pembrolizumab in Patients with Advanced Melanoma
2.1. Primary Objective
To assess the safety and tolerability of intravenous pembrolizumab with in combination with Intratumoral CAVATAK by incidence of dose-limiting toxicities (DLT).
2.2. Secondary Objectives
1. To assess the clinical efficacy of Pembrolizumab with in combination with Intratumoral CAVATAK in terms of of immune-related progression-free survival (irPFS) at 12 months, PFS hazard ratio, objective response rate (ORR), 1-year survival, overall survival (OS) and quality of life.
2. Assess the response of injected and non-injected melanoma deposits after CAVATAK and pembrolizumab.
3. Assess the time to initial response
4. Assess durable response rate at 6 months.
5. Assess peripheral blood for changes in T-cell phenotypes after CAVATAK and pembrolizumab.
6. Assess for T-cell immune response to known melanoma antigens during treatment.
A Phase 2, Multicenter, Single-arm Study to Assess the Safety, Feasibility, and Efficacy of Cell Transfer Therapy Using Autologous Tumor Infiltrating Lymphocytes (LN-144) Followed by IL-2 for Treatment of Metastatic Melanoma
To assess the safety and toxicities associated with the treatment regimen.
To assess the feasibility of TIL production, defined as the percentage of
patients with tumor resected from which TIL are successfully produced
(manufacture of more than 1.5 billion viable cells).
A Phase Ib/II Open-label, Multi-center Study of the Safety and Efficacy
of IMCgp100 in Combination with Durvalumab (MEDI4736) or Tremelimumab or the Combination of Durvalumab and Tremelimumab Compared to IMCgp100 Alone in Patients with Advanced Melanoma
Phase Ib: To characterize the safety and tolerability, and subsequently identify the MTD or RP2D, of the combination of durvalumab or tremelimumab with IMCgp100 (Arms 1 and 2) and tremelimumab + durvalumab with IMCgp100 (Arm 3).
Phase II: To evaluate the ORR of IMCgp100 using RECIST v.1.1 criteria as a single agent (Arm 4) and in combination with checkpoint inhibition with durvalumab (Arm 1), tremelimumab (Arm 2), or the combination of durvalumab and tremelimumab (Arm 3).
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.
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.