A Phase 2, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of MIT-001 in Prevention of Oral Mucositis in Patients Receiving CCRT for Locally Advanced HNSCC
Oral mucositis associated with cancer therapy carries a significant morbidity. OM is a common
complication in patients receiving CCRT used for treating HNSCC. Mucositis lesions can be
painful, affect nutrition and quality of life (QoL), and have a significant economic impact.
However, a definitive intervention regime has not been established. Therefore, it is
essential to develop appropriate treatment.
MitoImmune Therapeutics Inc. (hereafter referred to as Sponsor) has developed MIT-001 which
can scavenge abnormal levels of reactive oxygen species (ROS), enabling the cells to retain
mitochondrial membrane permeability and mitochondrial function. This eventually inhibits
additional ROS production, indicating that MIT-001 can prevent excessive inflammation caused
by ROS. In addition, MIT-001 may possibly 1) block inflammatory cytokine production via
inhibiting nuclear factor kappa B (NF kB) or inflammasome dependent pathways, 2) inhibit
necrosis/necroptosis via blocking high mobility group box 1 (HMGB1) mediated cytokine
production, and 3) balance regulation between T helper type 1/17 (Th1/17) and regulatory T
cells.
Based on the pathophysiological progression of CCRT-associated OM, initiated by direct injury
to basal epithelial cells which experience deoxyribonucleic acid (DNA) damage and increased
ROS levels, Sponsor expects the prevention of OM in patients receiving CCRT of locally
advanced HNSCC with MIT 001 by effectively scavenging increased ROS induced by CCRT.
A Phase III Trial of Perioperative Versus Adjuvant Chemotherapy for Resectable Pancreatic Cancer
PRIMARY OBJECTIVES:
I. To evaluate and compare overall survival (OS) in patients with resectable pancreatic
adenocarcinoma treated with perioperative fluorouracil, irinotecan hydrochloride, leucovorin
calcium and oxaliplatin (modified [m]FOLFIRINOX) and surgery versus up-front surgery followed
by adjuvant mFOLFIRINOX.
SECONDARY OBJECTIVES:
I. To evaluate and compare disease-free survival (DFS) in patients with resectable pancreatic
adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery
followed by adjuvant mFOLFIRINOX.
II. To evaluate and compare time to locoregional recurrence (TLR) in patients with resectable
pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front
surgery followed by adjuvant mFOLFIRINOX.
III. To evaluate and compare time to distant metastases (TDM) in patients with resectable
pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front
surgery followed by adjuvant mFOLFIRINOX.
IV. To evaluate and compare the R0 resection rate in patients with resectable pancreatic
adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery
followed by adjuvant mFOLFIRINOX.
V. To evaluate and compare rate of unresectability in patients with resectable pancreatic
adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery
followed by adjuvant mFOLFIRINOX.
VI. To evaluate rate of pathologic complete response in patients randomized to the
perioperative therapy arm.
VII. To evaluate and compare mFOLFIRINOX dose intensity delivered and number of cycles
received in patients with resectable pancreatic adenocarcinoma treated with perioperative
mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
VIII. To evaluate and compare adverse event profile in patients with resectable pancreatic
adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery
followed by adjuvant mFOLFIRINOX.
IX. To compare physical functioning, nausea/vomiting, and diarrhea, as measured with the
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life
Questionnaire-Core 30 (QLQ-C30) between patients with resectable pancreatic adenocarcinoma
treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by
adjuvant mFOLFIRINOX.
X. To prospectively assess the influence of diet, body mass index, weight loss, physical
activity, and other lifestyle habits on the disease-free survival and overall survival among
patients with localized pancreatic cancers.
XI. To assess the influence of diet, obesity, physical activity, and other lifestyle habits
on the risk of toxicity associated with chemotherapy.
XII. To evaluate the ability of computed tomography (CT)-based radiomics in distinguishing
post-neoadjuvant chemotherapy (NAC) fibrosis from viable tumor in patients randomized to the
perioperative therapy arm.
XIII. To determine whether CT-based radiomics retrieved from baseline examination may act as
non-invasive predictors of survival outcome in patients randomized to the adjuvant therapy
arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride
IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over
46-48 hours on days 1-3. Treatment repeats every 14 days for 8 cycles in the absence of
disease progression or unacceptable toxicity. Within 2-8 weeks of completing neoadjuvant
chemotherapy, patients undergo surgical resection. Patients then receive oxaliplatin IV over
2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on
day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for
4 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo surgical resection. Beginning 3-12 weeks after surgery, patients
then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and
leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3.
Treatment repeats every 14 days for 12 cycles in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up for 6 years.
A Phase 1b/2, Open-Label Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer
Colorectal cancer (CRC) is a major global health concern and the third most common cancer
worldwide. Amivantamab (also known as RYBREVANT or JNJ-61186372) is a fully human
immunoglobulin (Ig) G1-based bispecific antibody (Ab) directed against the epidermal growth
factor (EGF) and mesenchymal epithelial transition (MET) receptors, with evidence of
preclinical activity against non-small cell lung cancer (NSCLC) tumors with activating EGF
receptor (EGFR) mutations, the T790M and C797S second-site resistance EGFR mutations,
overexpressed wild-type EGFR, as well as with activation of the MET pathway. Amivantamab has
demonstrated activity in both EGFR- and MET-driven NSCLC, with preclinical evidence
demonstrating its ability to recruit immune effector cells. While two anti-EGFR antibodies
are incorporated as part of the SoC for CRC patients, MET is highly expressed or amplified in
subsets of CRC and additionally plays a role in mediating resistance to anti-EGFR treatments.
The study consists of up to 28 days screening period, treatment period will begin on Cycle 1
Day 1 (C1D1) (for Cohorts A, B, and C) or C1D -2 (for Ph1b-D, Ph1b-E, Cohorts D and E) with
the administration of the study treatment and continue as 28-day cycles until the end of
treatment visit, up to 30 days after discontinuation of study treatment. The safety of
amivantamab as a monotherapy or in addition to SoC chemotherapy will be assessed by physical
examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status (PS),
laboratory tests, vital signs, monitoring of adverse events, and concomitant medication
usage. The total duration of this study will be up to 4 years 3 months.
Phase 1 Trial of Intralesional Immunotherapy With IFx-Hu2.0 Vaccine in Patients With Advanced Non-melanoma Skin Cancers
Approximately twenty adult patients (≥ 18 years of age), of any sex, ethnicity, and race with
histologically confirmed advanced non-melanoma skin cancers with accessible lesions, will be
eligible for study enrollment and treatment with IFx-Hu2.0 (i.e. 20 total patients across
both indications). These types of advanced non-melanoma skin cancers are very rare in the
pediatric population (< 18 years of age) with only scattered case reports. The potential for
development of this product for pediatric subjects with non-melanoma skin cancers will be
evaluated after the results of this study are available.
Patients must have at least one injectable lesion, defined as an easily palpable superficial
lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized,
stabilized by palpation, and is superficial enough to enable intralesional injection.
To be eligible for this study, patients must have progressed despite standard therapy(ies),
or are intolerant to or refused standard therapy(ies).
Enrollees will receive IFx-Hu2.0 as a monotherapy at up to three-time points. Depending on
the number of accessible lesions, a patient could receive up to three doses across three
lesions (one dose per lesion). The maximum number of lesions to be injected at any time point
under this protocol is three lesions. Blood will be collected from these patients prior to
treatment administration at every drug administration visit. These samples will be used to
perform CBC and clinical chemistry tests. A urine sample will be obtained for urinalysis for
protein and blood at the same frequency. Blood samples will also be drawn at the same
intervals for immune response evaluation as well.
This is primarily a safety study that is designed to evaluate IFx-Hu2.0 monotherapy and
provide foundational evidence to potentially support further studies investigating IFx-Hu2.0
+ anti-PD-1 combination therapy for patients with non-melanoma skin cancers.
RT CHARM: Phase III Randomized Trial of Hypofractionated Post Mastectomy Radiation With Breast Reconstruction
PRIMARY OBJECTIVES:
I. To evaluate whether the reconstruction complication rate at 24 months post radiation is
non-inferior with hypofractionation.
SECONDARY OBJECTIVES:
I. To evaluate the incidence of acute and late radiation complications, based on Common
Terminology Criteria for Adverse Events (CTCAE) 4.0 toxicity.
II. To evaluate the local and local regional recurrence rate. III. To compare reconstruction
complication rates based on reconstruction method (autologous +/- implant versus [vs] implant
only) and timing of reconstruction received (immediate vs. intent for delayed).
TERTIARY OBJECTIVES:
I. To evaluate reconstructed breast photographic cosmetic scores with hypofractionated
radiation compared to standard fractionation 24 months after radiation.
II. To evaluate reconstructed breast photographic cosmetic scores 24 months after radiation
based on the method and timing of reconstruction received.
III. To estimate the incidence of arm lymphedema by treatment arm. IV. To compare physical
well-being, psychosocial well-being, sexual well-being, satisfaction with
breast/nipples/abdomen, and satisfaction with overall outcome between the treatment arms at
24 months after radiation.
V. To estimate patient satisfaction with trial participation by treatment arm as measured by
the Was It Worth It Questionnaire at 24 months after radiation.
VI. To compare the direct and indirect patient costs for radiation therapy by treatment arm.
VII. To compare patient reported total health care service utilization 12 months after the
completion of radiation.
VIII. To compare the economic impact of treatment. IX. To analyze polymorphisms in MDM2 and
in genes including TP53, ATM, TGFB1, IL4, IL6, and IL10 and determine correlations with a
higher likelihood of adverse radiation reactions (radiation sensitivity) and with toxicities.
X. To analyze polymorphisms in MDM2 and in genes including TP53, ATM, TGFB1, IL4, IL6, and
IL10 to determine correlations with secondary endpoints such as local-regional control.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients undergo radiation therapy daily on Monday-Friday for 5-6 weeks.
GROUP II: Patients undergo hypofractionated radiation therapy daily on Monday-Friday for 3-4
weeks.
After completion of study, patients are followed up for 5 years.
A Phase 1, Open-Label, Non-randomized, Dose-Escalating Safety, Tolerability, and Pharmacokinetic Study of TAS-114 in Combination With Capecitabine in Patients With Advanced Solid Tumors
In animal models, co-administration of TAS 114 and capecitabine has shown antitumor effects
exceeding the maximum efficacy obtained by capecitabine alone. Developing a novel
chemotherapy based on the combined use of TAS-114 and capecitabine may fulfill the need for
more efficacious treatment for patients with advanced solid tumors.
The study, evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor
activity of the TAS-114/ capecitabine regimen in patients with advanced solid tumors, will be
conducted in two parts: a Dose-Escalation Phase (Part 1) to determine the MTD; and an
Expansion Phase (Part 2) to further evaluate the safety and preliminary efficacy with the
MTD.
0C-10-4: A Phase Ia/Ib Clinical Trial of PRI-724 in Patients with Advanced Solid Tumors
Despite recent progresses in directed chemotherapy, the modern anti-cancer armamentarium only eradicates the majority of drug-sensitive and differentiated tumor cells. Unfortunately, to date no effective therapeutic solution has been developed to treat cancer stem cells. Based on pre-clinical research utilizing CREB-binding proteins/ beta-catenin antagonists, it is hypothesized that such antagonists can target CSCs and thereby offer a novel anti-tumor therapeutic approach.This is a Phase Ia/Ib clinical trial of PRI-724 in patients with advanced solid tumors. It has 2 arms:Phase Ia Accelerated Phase/Dose Escalation and Phase Ib Dose Expansion: PRI-724 MTDThe primary objective of the study is to determine the maximally tolerated dose (MTD) of PRI-724 when administered as a continuous 7-day intravenous infusion to patients with solid tumors. This has been completed in Phase 1a of the study. The Phase 1b will determine the MTD of PRI-274 when combined with mFOLFOX6 in patients with colorectal carcinoma.The secondary objectives are to describe the side effects experienced in both parts of the study, determine the pharmacokinetic profile of PRI-724 and C-82, assess anti-tumor activity, assess the genetic expression of survivin and the effect PRI-724 has on survivin, and assess the affect of C-82 on hair follicle neogenesis and collagen expression. The study also has an exploratory objective to obtain matrix metalloproteinase-7 (MMP7) levels in serum via enzyme-linked immunosorbent assay (ELISA) testing.The starting dose and dose escalation scheme was selected to provide an adequate safety margin based on Good Laboratory Practices (GLP) 28-day continuous iv infusion nonclinical studies. The study consists of accelerated Phase Ia and dose escalation at standard 3+3 phase. Each cycle is defined as 7-day continuous intravenous (iv) infusion followed by a 7-day rest period. At the Maximally Tolerated Dose (MTD), Phase Ib will commence where 18 patients with advanced colorectal cancer who have progressed or whose tumors are no longer responsive to standard therapies will be enrolled.The exact number of patients enrolled will depend on the toxicity observed in each dose escalation cohort and the number of cohorts required to reach MTD.The mRNA level of surviving will be measured in both Phase Ia and Ib. If mRNA level of surviving at day 8 of PRI-724 treatment is decreased 30% or more compared to the level prior to PRI-724 treatment, it suggests that PRI-724 inhibits surviving. In addition to this, assessment will be made of clinical endpoints including tumor response by RECIST and progression-free survival by tumor specimen and circulating tumor cells in every cohort.A typical electronic data capture (EDC) system will be used for data collection.Statistical analysis will be carried out by USC Norris Comprehensive Cancer Center Biostatistics core using SAS Version 9.0 or later.
Powered by
SC CTSI