|Protocol||Trial Name and Objective|
Selecting for Cetuximab Responders in Advanced Head and Neck SCC
The purpose of this protocol is to assess the feasibility/safety of a neoadjuvant cetuximab protocol in advanced head and neck SCC. The overall treatment strategy expressed in the protocol is to treat stage III/IV head and neck SCC patients (oropharynx, larynx, hypopharynx) with 3 weeks of neoadjuvant cetuximab, select those patients who respond (develop cetuximab related folliculitis or at least a partial response by CT recist criteria) and then treat them with concurrent external beam radiation therapy (EBRT) and cetuximab. Those patients who do not respond will receive concurrent cisplatinum and EBRT.
The primary objective of this protocol is to assess the safety of adding the three weeks of neoadjuvant cetuximab i.e., what percentage of patients' cancers will progress during those three weeks of neoadjuvant cetuximab by recist CT criteria. The hope is that the data derived from this study will lead to a large phase II or phase III trial.
In addition, this will be a unique platform to assess molecular markers, as we will obtain biopsies of tumor before and after 3 weeks of neoadjuvant cetuximab, as well as a skin biopsy before therapy. We plan to do DNA and RNA sequencing for these samples, in this manner checking for possible escape mechnisms from the EGFR pathway in response to anti-EGFR therapy, and for other molecular correlates to 2 year locoregional response.
Salvage Therapeutic Radiation with Enzalutamide and ADT in Men with Recurrent Prostate Cancer (STREAM)
Primary Objective: to describe the 2 year progression-free survival in men with recurrent PSA-only disease after prostatectomy receiving combined enzalutamide and standard androgen-deprivation therapy with salvage radiation therapy and who have had testosterone recovery to greater than 100 at 24 months.
Secondary Objectives: (1) to determine the proportion of men at 1, 2 and 3 years with a PSA of less than 0.1 ng/mL and testosterone receovery to greater than 100. (2) to describe the 3 year progression-free suvival in men receiving combined enzalutamide and standard androgen-deprivation therapy with salvage radiation therapy and who have had testosterone recovery to greater than 100. (3) to describe the biochemical (PSA) progression free survival over time. (4) to describe the PSA nadir. (5) to describe the time to testosterone recovery. (6) to describe the safety profile of combination enzalutamide, ADT, and XRT.
Radiation from Interventional Cardiovascular Procedures and Risk of Breast Cancer
Hypothesis: The primary hypotheses underlying this project are as follows: (1) Exposure to IR delivered during ICPs will lead to an increased risk of developing breast cancer in our cohort of patients and (2) As ICPs have become longer and more complex, the procedural changes over time may increase the relative risk of developing breast cancer.
Aim 1: To quantitate the exposure to IR delivered to patients in New Jersey who underwent interventional cardiovascular procedures.
Aim 1A: To calculate population based rates of low, moderate, high, and very high effective doses of IR from interventional cardiovascular procedures.
Aim 1B: To describe the specific types of interventional cardiovascular procedures among persons for whom the long-term risks of IR exposure are most relevant.
Aim 2: To quantitate the risk of developing breast cancer in patients admitted for cardiovascular disease in New Jersey who had received IR from interventional cardiovascular procedures by linking MIDAS with the NJSCR. We will compare the risk of developing breast cancer in patients exposed to IR (ICP group) and unexposed patients (non-ICP group).
Aim 2A: To link the MIDAS groups from Aim 1 to the NJSCR, and classify cohort members by breast cancer diagnosis.
Aim 2B: To longitudinally compare the IR exposed group with the matched unexposed group of patients who did not receive IR from interventional cardiovascular procedures.
Aim 2C: To estimate the risk of developing breast cancer based on rates of low, moderate, high, and very high effective doses of radiation from interventional cardiovascular procedures.
Aim 3: To determine systemic interrelationships between changes in interventional cardiovascular procedures over time on the incidence of breast cancer and associated rates of morbidity and mortality.
Retrospective Comparative Analysis of Hematologic Toxicities in Patients Receiving Chemo-Radiotherapy in Rectal Cancers Versus Chemotherapy in Colon Cancers.
To quantify bone marrow toxicity after radiation therapy in rectal cancer patients compared to bone marrow toxicity without radiation therapy in colon cancer patients.
COG-ACNS0332: Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients
1. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/PNET patients.
2. To determine whether Isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients.
3. To compare residual disease response to radiation alone versus radiation plus carboplatin.
4. To identify molecular prognostic indicators suitable for patient stratification in future trials.
5. To evaluate the HRQOL during phases of active treatment specific to treatment modalities.
6. To describe the neuropsychological functioning of the study population and to evaluate the relationship
between neuropsychological status and health related quality of life.
COG ACNS0831: Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients with Newly Diagnosed Ependymoma Ages 1 to 21 years
1. To determine the event free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with post-operative conformal radiation therapy (cRT) and then randomized to receive or not receive four cycles of post radiation maintenance chemotherapy with vincristine, cisplatin, etoposide and cyclophosphamide (VCEC).
2. To estimate the EFS and OS of children with incompletely resected ependymoma who are unable to achieve a complete response (CR) by a) post-operative induction chemotherapy or by b) second surgery who will then be non-randomly assigned to cRT followed by four cycles of maintenance chemotherapy (VCEC)
3. To further evaluate the EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second resection or children who achieve a CR to short course induction chemotherapy following first surgery.
RTOG 1205: Randomized Phase II Trial of Concurrent Bevacizumab and Re-Irradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma
To establish an improvement in overall survival in recurrent GBM patients receiving bevacizumab and re-irradiation compared with patients receiving bevacizumab alone.
Secondary objectives include:
To estimate and compare the rate of objective response in patients with measurable disease.
To estimate and compare the 6-month progression-free survival rate.
To estimate and compare progression-free survival.
To estimate and compare the rate of treatment adverse events.
To estimate and compare the rate of ?grade 3 acute or delayed CNS toxicity.
COG ACNS1123: Phase 2 Trial of Response-Based Radiation Therapy for Patients with Localized Central Nervous System Germ Cell Tumors (CNS GCT)
1. To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole ventricular field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young adults (ages 3 to Ü 21 years) with localized non-
germinomatous germ cell tumor (NGGCT) who have a magnetic resonance imaging (MRI) and tumor marker criteria (CSF and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with negative tumor markers who undergo a second-look surgery and are found to have only mature teratoma, residual scar or fibrosis and fit the definition of CR/PR after second-look surgery.
2. To determine, as measured by the 3-year PFS rate and patterns of failure, whether simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating children and young adults (ages 3 to Ü 21 years) with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCG Â) Ü50 mIU/ml
3. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (Germinoma) using the ALTE07C1 protocol. This objective will be assessed independently for the two strata.
4. To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated with 30.6Gy WVI and involved field focal (IFR) boost to 54Gy.
5.To estimate the PFS and OS distributions of
localized germinoma patients who present with
a) serum and/or CSF hCGÂ Ü50mIU/ml and b) serum and/or CSF hCG
Â> 50mIU/ml and Ü100mIU/ml.
Childrens Oncology Group ARST1321:Pazopanib Neoadjuvant Trial In Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib (NSC# 737754, IND# 118613)
1.1.1 To identify the dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric and adult patients newly diagnosed with unresected intermediate- and high-risk NRSTS.
1.1.2 To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative chemoradiation versus preoperative
chemoradiation alone for potentially resectable > 5 cm, Grade 3 intermediate to high risk chemotherapy-sensitive NRSTS in the Phase II portion of the study for this cohort. 1.1.3 To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for potentially resectable intermediate to high risk adult and pediatric NRSTS in the Phase II portion of the study for this cohort (using a Phase II decision rule to go onto the Phase III portion of the study).
1.1.4 To compare the rates of event-free survival (EFS) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for localized intermediate to high risk adult and pediatric NRSTS in the Phase III portion of the study for this cohort if the Phase II decision rule is passed.
1.2 Secondary Objectives
1.2.1 To estimate the rates of local failure, regional failure, distant metastasis free survival, disease-free survival, and overall survival with the addition of pazopanib to preoperative chemoradiation or preoperative radiation in intermediate to high
risk adult and pediatric NRSTS.
1.2.2 To compare the pattern of recurrence (local, regional and distant) between preoperative chemoradiation or radiation with the addition of pazopanib for adult and pediatric NRSTS. 1.2.3 To define the toxicities of ifosfamide and doxorubicin chemotherapy and radiation
when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.
1.2.4 To define the toxicities of preoperative radiotherapy when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.
AALL1231: A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239; IND# 58443) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy)
1 To compare EFS in patients with newly diagnosed T-ALL and T-LLy who are randomized to a modified ABFM backbone versus bortezomib plus the modified ABFM backbone.
2.To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy based on the results of UKALL 2003, which includes a dexamethasone-based Induction, additional doses of pegaspargase (PEG-ASP) during Induction and Delayed Intensification (DI), and dexamethasone pulses during Maintenance therapy
3. To determine if prophylactic cranial radiation therapy (CRT) can be safely and effectively eliminated in the 85-90% of T-ALL patients classified asstandard or intermediate risk.
4.To determine the proportion of EOC MRD ? 0.1% T-ALL patients who become MRD negative (undetectable by flow cytometry) after intensification of chemotherapy, using three high risk (HR) BFM blocks, and to compare EFS between the patients who become MRD negative after the three HR BFM blocks and continue on chemotherapy with those who continue to have detectable MRD and are eligible for other treatment strategies, including hematopoietic stem cell transplant
Similarly, to compare the EFS between very high risk (Induction failure) T-LLy
patients treated with HR BFM intensification blocks who have partial or complete response (PR or CR) with those who do not respond (NR).
5. To investigate the prognostic significance of Day 29 BM MRD in T-LLy patients.
6. To determine if protein expression patterns can predict bortezomib response and drug resistance in T-ALL
7. To analyze and target relevant signaling pathways in T-ALL blasts, focusing on Early T cell Precursor ALL
NRG-BN001: Randomized, Phase II Trial of Hypofractionated Dose-escalated Photon IMRT or Proton Beam Therapy versus Conventional Photon Irradiation with Concomitant and Adjuvant Temozolomide in Patients with Newly Diagnosed Glioblastoma.
To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves overall survival, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.
2.2.1 To indirectly compare dose-escalated and -intensified photon IMRT to dose-escalated and -intensified proton beam therapy in terms of overall survival.
2.2.2 To indirectly compare and record toxicities of dose-escalated and -intensified photon IMRT versus dose-escalated and -intensified proton beam therapy and directly compare the toxicities of these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide
2.2.3 To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves perceived cognitive symptom severity, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.
2.2.4 To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves neurocognitive function, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.
2.2.5 To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves perceived cognitive symptom severity, as compared to dose-escalated and -intensified photon IMRT, and to directly compare symptom burden with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide
2.2.6 To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves neurocognitive function, as compared to dose-escalated and -intensified photon IMRT, and to directly compare neurocognitive function with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide
2.3.1 Tissue banking for future translational science projects that will be determined based on the state of the science at the time the primary endpoint is reported and will be submitted to NCI for review and approval.
2.3.2 To prospectively compare CD4 lymphopenia between dose-escalated and intensified proton beam therapy, dose-escalated and -intensified photon IMRT, and standard-dose photon irradiation and determine whether CD4 lymphopenia impacts overall survival.
2.3.3 To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout radiation therapy processes, including imaging, simulation, patient immobilization, target and critical structure definition, treatment planning, image guidance and delivery.
X To establish feasibility anand clinical relevancy of quality assurance guidelines
X To evaluate efficacy of quality assurance tools
2.3.4 To explore the most appropriate and clinically relevant advanced and standard MRI imaging parameters
X To evaluate the feasibility of differentiating pseudo-progression and true progression in a multi institutional setting using MR diffusion and perfusion imaging.
X To evaluate for early, imaging biomarkers of response and overall survival.
A RANDOMIZED PHASE III TRIAL COMPARING AXILLARY LYMPH NODE DISSECTION TO AXILLARY RADIATION IN BREAST CANCER PATIENTS (cT1-3 N1) WHO HAVE POSITIVE SENTINEL LYMPH NODE DISEASE AFTER NEOADJUVANT CHEMOTHERAPY
To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive SLN(s) after completion of neoadjuvant chemotherapy.
2.2 Secondary objectives
2.2.1 To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy.
2.2.2 For each treatment arm
* To obtain an estimate of the distribution of residual disease burden scores.
* To estimate the distribution of overall survival.
2.3 Correlative objectives
* To estimate the incidence of arm lymphedema.
* To estimate the incidence of breast lymphedema for patients who underwent breast conserving surgery based on the specific treatment rendered to the axilla.
A phase II trial of concurrent chemoradiation with consolidation Pembrolizumab (MK-3475) for the treatment of inoperable or unresectable stage III non-small cell lung cancer (NSCLC): LUN14-179
To determine if consolidation therapy with Pembrolizumab (MK-3475), following concurrent chemoradiation improves time to death or distant metastatic disease, depending on which occurs first, in patients with inoperable or unresectable stage IIIA or IIIB NSCLC. Distant metastasis is defined as anything that is outside of the radiation field.
h To determine if consolidation therapy with Pembrolizumab (MK-3475), following concurrent chemoradiation improves progression free survival (PFS) and overall survival (OS) in patients with inoperable or unresectable stage IIIA or IIIB NSCLC.
h To assess toxicity and tolerability of consolidation therapy with Pembrolizumab (MK-3475), following concurrent chemoradiation in patients with inoperable or unresectable stage IIIA or IIIB NSCLC.
h Time To Death in evaluable set
To assess PD-L1 expression levels in the tumor samples of patients with inoperable or unresectable stage IIIA or IIIB NSCLC and correlate with time to distant metastatic disease, tumor histology, PFS, OS, and treatment toxicity
RTOG 1112: Randomized Phase III Study of Sorafenib Versus Stereotactic Body Radiation Therapy Followed by Sorafenib in Hepatocellular Carcinoma
2.1 Primary Objective
2.1.1 To determine if SBRT improves overall survival in HCC patients treated with Sorafenib
2.2 Secondary Objectives
2.2.1 To determine the difference in time to progression (TTP) and progression-free survival (PFS) in
HCC patients treated with Sorafenib compared to SBRT followed by Sorafenib
2.2.2 To measure differences in toxicity in HCC patients treated with Sorafenib versus SBRT followed
2.2.3 To measure vascular thrombosis response post Sorafenib versus SBRT followed by Sorafenib
2.2.4 To measure differences in Health Related QOL and quality-adjusted survival in HCC patients
treated with Sorafenib compared to SBRT followed by Sorafenib
2.2.5 Collection of biospecimens for future correlative studies to investigate differences in potential
biomarkers in patients treated with Sorafenib versus SBRT followed by Sorafenib
CHILDREN'S ONCOLOGY GROUP AHOD1331: A Randomized Phase III Study of Brentuximab Vedotin (SGN-35, IND #117117) for Newly Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Adolescents.
1. To assess the event free survival (EFS) of a novel regimen incorporating brentuximab vedotin (Bv; AdcetrisTM) in the chemotherapy backbone of doxorubicin (Adriamycin), vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVEPC) in newly diagnosed high-risk cHL compared to those treated with ABVE-PC.
2. To determine whether children/adolescents with high-risk cHL treated with Bv-AVEPC have a higher rate of early response (determined by FDG-PET) and a reduction in response-directed radiation therapy (RT) compared to those treated with ABVE-PC.
3. To compare the rate of neuropathy (> Grade 3) among patients treated on the Bv-AVEPC (experimental arm) to patients treated on the ABVE-PC (standard arm).
4. To validate and compare the Childhood Hodgkin International Prognostic Score (CHIPS) to conventional Ann Arbor Stage (Stages II B with bulk, III B, IV A or B) in predicting outcome in high-risk childhood cHL.
5. To determine the incidence of preferentially expressed antigen in melanoma (PRAME) and testis-specific antigens in EBV- cHL tumors and the incidence of EBV antigens (EBNA1, LMP1, LMP2) in EBV+ cHL tumors, with the goal of developing strategies to integrate cellular therapy into treatment for newly diagnosed high-risk cHL.
6. To incorporate qualitative visual FDG-PET into response-directed treatment algorithms and explore quantitative FDG-PET and CT definitions of tumor burden and response for incorporation into next generation pediatric cHL risk-stratification schemes.
7. To evaluate the reduction in normal tissue irradiation associated with the current treatment approach compared to the volume of historic IFRT fields.
8. To evaluate EFS and patterns of relapse following protocol-specified RT utilization and treatment volumes.
Patient Reported Outcomes (PRO) of Peripheral Neuropathy and Health-Related Quality of Life
9. To characterize the extent of chemotherapy induced peripheral neuropathy (CIPN), as reported by patients and parent proxies, through serial administration of the FACT-GOG-NTX.
10.To describe the Health-Related Quality of Life (HRQL) consequences of peripheral neuropathy over time by correlating total neuropathy scale scores with the individual items with the CHRIs-Global scale (e.g., physical health, pain, emotional functioning).
11.To perform a cross validation of the FACT-GOG-NTX with the TNS-PV to determine the performance of both measures with the use of brentuximab vedotin in a limited institutional approach in children and adolescents with cHL
12.To assess the resource use and cost implications of Bv in combination with chemotherapy and radiotherapy (RT) for newly diagnosed high-risk cHL in children and adolescents
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.
Use of the BioZorb implant to delineate the tumor excision site following lumpectomy
To document findings and outcomes for patients who have the BioZorb surgical tissue marker implanted following partial mastectomy or "lumpectomy" in a broad spectrum of clinical practice settings.
1. Surgical: identify the surgical sub-groups that physicians choose for implantation of the BioZorb; understand various cavity closure techniques that are used following tumor excision and how these techniques are utilized, and monitor surgical outcomes such as wound healing, cosmetic outcomes and surgeon satisfaction.
2. Radiation Oncology: identify the various types of radiation therapy delivered following lumpectomy, record the planned treatment volumes of tissue treated and document the utility of BioZorb for treatment planning and delivery.
3. Patient Satisfaction: patients rate their overall satisfaction with the breast appearance, patient acceptance, and treatment outcomes
NSABP B-51: A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients with Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy
NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT
To evaluate whether the addition of regional nodal radiation to chestwall and/or breast radiation will significantly reduce the rate of events for invasive breast cancer recurrence-free interval (IBC-RFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.
PRIMARY AIMS: Ipsilateral recurrence-free interval, defined as time from randomization until invasive local, regional, or distant recurrence, or death from breast cancer.
SECONDARY AIMS: Overall and disease-free survival, characterization of locoregional recurrence patterns, second invasive and/or in situ cancers, QOL, molecular marker predictors, effectiveness of adjuvant radiation techniques.