Phase I Open Label, Multi-center, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered CUDC-907, a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma or Multiple Myeloma
This is a Phase I, open-label, multi-center dose-escalation trial evaluating the safety and
tolerability of CUDC-907 as a single agent administered orally, once daily, to patients with
relapsed or refractory lymphoma or multiple myeloma. The following dosing schedules may be
examined, all consisting of 21-day cycles and including:
(i) continuous once daily (QD), (ii) twice weekly on Days 1, 4, 8, 11, 15, 18 (BIW) (iii)
thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, 19 (TIW) (iv) four days on/three days off
on Days 1-4, 8-11, and 15-18 (4/3), and (v) five days on/two days off on Days 1-5, 8-12, and
Sequential dose escalation cohorts of oral CUDC-907 are planned. Subject enrollment and dose
escalation will proceed according to a standard 3+3 design. In the absence of DLT, each
subject will be treated for a minimum of 21 days, and may continue to receive additional
treatment until disease progression has been documented or other treatment discontinuation
criteria have been met.
MTD or BED expansion cohorts of up to 36 evaluable (e.g., up to 12 subjects in each of 2 or
3 specific tumor types or subtype) to better define the safety, tolerability and preliminary
antitumor and pharmacodynamic activity of the study treatment, as well as suitability as an
RP2D and schedule.
Safety and tolerability will be assessed by the incidence and severity of adverse events as
determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE v4.03). A Safety Review Committee (SRC) comprised of the Medical Monitor, Principal
Investigators, and Sponsor representatives, will be convened to review safety information
and to decide upon dose escalation and further subject enrollment.
The antitumor activity of study treatment will be assessed according to standard response
criteria as appropriate for each individual subject's tumor type (e.g., Revised Response
Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple
Exploratory biological markers of activity will be assessed in peripheral blood mononuclear
cells (PBMC), plasma and tissue specimens (skin, tumor and bone marrow samples, where
16M-14-1: Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma
Multiple myeloma is a type of blood cancer caused by the transformation and uncontrolled multiplication of plasma cells (a type pf blood cell). It is the second most common hematological malignancy and is invariably fatal. Myeloma cells expand in the bone marrow causing skeletal destruction, high calcium levels, kidney failure and anemia.
The study population will consist of multiple myeloma patients requiring therapy who have relapsed and/or are refractory to their last therapy and have been treated with at least 1, but not more than 5 lines of multiple myeloma therapy.
The study drug, oprozomib works by preventing the breakdown of certain proteins in cells, causing the cells to die. Studies with oprozomib have been able to demonstrate the treatment potential for blocking proteasomes (protein complexes) in multiple myeloma. These proteasomes main function is to degrade unneeded or damaged proteins.
The primary objective of Phase 2 is to estimate the overall response rate.
This study is an open-label, Phase 1b/2, multicenter study in which participants will receive oprozomib administered orally, once daily, in combination with dexamethasone as follows:
Days 1, 2, 8, and 9 of a 14-day cycle;
Treatment will be administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason.
USC will only participate in Phase 2. The Phase 2 portion of this study will be initiated at the sponsors discretion using the recommended dose determined from 1 or both dosing schedules. The total study duration is expected to be approximately 26 months.
A Phase II Randomized Study Comparing Two Doses of Carfilzomib (NSC-756640) With Dexamethasone for Multiple Myeloma Patients With Relapsed or Refractory Disease
I. To evaluate and compare progression free survival (PFS) of two different doses of
carfilzomib with dexamethasone in multiple myeloma (MM) patients with relapsed and/or
I. To evaluate and compare response rates (RR) for each arm. II. To evaluate response rates
(RR) for patients that relapse on low dose carfilzomib and subsequently cross-over to high
III. To evaluate the safety of this combination for this patient population. IV. To evaluate
overall survival (OS).
I. To explore the molecular variability in MM cells obtained from extramedullary bone marrow
II. To explore the role of positron emission tomography (PET) scanning in assessing disease
burden and as a tool to assess treatment response.
III. To explore changes in left ventricular ejection fraction (LVEF) in patients with
relapsed or refractory multiple myeloma treated with low dose carfilzomib or high dose
carfilzomib plus dexamethasone.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive dexamethasone intravenously (IV) and low-dose carfilzomib IV over
2-10 minutes on days 1, 2, 8, 9, 15, and 16. Patients with progression cross-over to Arm II.
ARM II: Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on
days 1, 2, 8, 9, 15, and 16.
Note that for the first course of treatment on both arms carfilzomib is given at a reduced
rate to assess toxicity.
In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years
from initial registration.
S0702, "A Prospective Observational Multicenter Cohort Study to Assess The Incidence of Osteonecrosis of the Jaw (ONJ) in Cancer Patients with Bone Metastases Starting Zoledronic Acid Treatment.
This study is about Zoledronic acid that falls under a category of drugs called bisphosphonates. Bisphosphonates are sometimes given to patients who have cancer that has spread to their bones because it can lower the chances of getting fractures and reduces bone pain. Usually, zoledronic acid is well tolerated by patients, but there has been an increase in the number of reported cases of osteonecrosis of the jaw (ONJ). Symptoms associated with ONJ are swelling of the soft tissue around the jaw, infection, loosening of teeth, drainage, and exposed jaw bone. There is concern about the association of ONJ with bisphosphonate therapy.The primary objective of this study is to prospectively assess, how often ONJ occurs in patients who are being treated with zoledronic acid during a 3 year time period after starting treatment.This is not a treatment study. This study involves collecting information about the treatment with zoledronic acid and collecting information about participants general health and medical history, oral health and dental history and pain assessment through questionnaires.Participants go through some exams, tests or procedures that are part of regular cancer care, like Blood work, Dental exam, Oral x-rays, Medical and dental history, Physical exam.Every six months for up to three years, participants will be asked to provideInformation regarding current treatment for metastatic bone diseaseInformation about any health problems they are havingInformation about their medical history, treatments and physical examInformation regarding their oral health, dental history and exams and pain assessmentIf at any time participants are diagnosed with osteonecrosis of the jaw (ONJ)Every three months for up to three years, they will be asked to provideInformation regarding current treatment for ONJInformation about any health problems they are having with the zoledronic acidInformation regarding oral complications and recent dental proceduresUpdated information on their medical history, physical exam, and treatmentSubmission of dental x-rays and scansThe primary endpoint is the diagnosis of confirmed ONJ. For statistical consideration the goal of this study is to estimate the cumulative incidence rate of confirmed ONJ associated with zoledronic acid at 3 years in patients with bone metastases.About 3,500 people will take part in this study nationally; 200 research participants from USC will take part in this study.