An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma
The purpose of this research study is to find out whether adding an experimental vaccine
called rindopepimut (also known as CDX-110) to the commonly used chemotherapy drug
temozolomide can help improve the life expectancy of patients with newly diagnosed, resected
EGFRvIII positive glioblastoma.
The duration of participation in this study may be up to 5 years. After you are screened and
enrolled in the study, you will be administered temozolomide and either rindopepimut/GM-CSF
or KLH until either disease progression or intolerance to the medications. If your tumor
progresses while on this study, your doctor may treat you with other therapies that are not
part of the study.
A Phase 2 Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Angiogenesis plays a central role in the progression of epithelial ovarian cancer. In mouse
models, VEGF-inhibitors diminish ovarian tumor growth, metastasis and malignant ascites
formation. Independent Phase 2 trials have demonstrated single-agent activity for bevacizumab
in recurrent ovarian cancer, and randomized controlled Phase 3 trials are ongoing in the
first-line setting (GOG 0218 and ICON-7) and for recurrent disease (GOG 0213, OCEANS).
TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on vascular
endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical
models. In a Phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction
in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. We
hypothesize that TRC105 will have single-agent activity in recurrent ovarian cancer. By
targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibitors which
could represent a major advance in ovarian cancer therapy.
Phase 1/2, First-in-Human, Dose-Escalation Study of X-396 (Ensartinib) in Patients With Advanced Solid Tumors and Expansion Phase in Patients With ALK-positive Non-Small Cell Lung Cancer
This is the first study of X-396 (ensartinib) in humans and the investigational drug will be
given as a once or twice daily oral dose in 28 day cycles until there is disease progression
or unacceptable safety issues. X-396 will be given to small groups of patients (1 - 6) at
each dose level and the patients will be observed to see if there are any adverse safety
effects. As long as there are no unacceptable safety issues after 28 days, the dose of X-396
will be increased for the next group of patients. This process will continue until the
maximum tolerated dose (MTD) of X-396 is reached. Once the MTD is reached, up to 170
additional patients will also be given X-396 to further determine the activity of X-396 in
patients with ALK-positive non-small cell lung cancer. These additional patients will be
enrolled in the following expansion cohorts: ALK TKI-naïve patients, patients that progressed
on crizotinib, patients that progressed on one or more 2nd generation ALK TKIs (patients may
or may not have also received prior crizotinib), including patients with asymptomatic CNS
metastases.
A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer
Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3,
VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models.
The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can
provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or
FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in
patients not known to have FGF abnormalities.
Based on these results, is study is designed to explore the safety and anti-tumor activity
of daily lucitanib in breast cancer patients with and without alterations of the FGF
pathway.
A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer
accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with
NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted
therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have
mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the
gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs
eventually progress, and in approximately 50% of cases, progression is due to development of
an additional mutation called T790M. There are currently no approved therapies for patients
who progress on TKIs. Rociletinib may provide an effective therapy for a patient population
with few alternative treatment options. Nonclinical data demonstrate that rociletinib
inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells
with the T790M mutation, thus providing possible therapeutic benefit in patients who have
developed T790M-mediated resistance to first generation TKIs.
This is a two-part, open-label study of oral rociletinib administered daily in previously
treated NSCLC patients who have documented evidence of an activating mutation in the EGFR
gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or
afatinib.
This study will include 2 parts:
Phase 1 (completed enrolment): Dose-escalation Period with 21-day cycles; optional Treatment
Extension Period starting on Day 22
Phase 2 (currently enrolling): Evaluation of activity and safety in patients with the T790M
EGFR mutation who have:
Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of
previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR
directed therapy received and also had no more than one previous line of chemotherapy
A Phase 1, Open-Label, Dose-Escalation, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MT-0169 in Patients With Relapsed or Refractory Multiple Myeloma
The drug being tested in this study is called MT-0169. The study will evaluate the safety,
tolerability, preliminary efficacy, PK, pharmacodynamics, and immunogenicity of MT-0169
monotherapy in participants with RRMM.
The study will enroll up to 54 total participants.
The purpose of this study is to evaluate the safety and tolerability of MT-0169 in subjects
with relapsed or refractory multiple myeloma (RRMM) and to estimate the maximum tolerated
dose (MTD) or the recommended Phase 2 dose (RP2D).
MT-0169 will be given as an intravenous (IV) infusion over 60 minutes on the same day every
week (i.e., days 1, 8, 15 and 22) or every 2 weeks (i.e., days 1 and 15) of each cycle. A
cycle is defined as 28 days.
A subject may participate for the following three (3) periods:
Screening Period - up to 28 days before first dose of MT-0169 Treatment Period - active
period where a subject will receive doses of MT-0169 over a 28-day treatment period Follow-up
Period - up to 12 months after the last patient in the study to receive the last dose of
MT-0169.
Participants can receive MT-0169 until the cancer worsens, side effects prevent further study
treatment, or until the participant leaves the study for other reasons decided by the
participant, the study doctor, or the sponsor of the study. After treatment has finished,
participants will have a check-up of their disease status every 12 weeks.
This multi-center trial will be conducted in the United States. The overall duration of the
study will vary for each participant because they will receive study treatment until
unacceptable toxicity, withdrawal of consent, death, termination of the study by the sponsor,
or fulfillment of another discontinuation criterion. Participants will be followed up for 30
days after the last dose of study drug for a follow-up assessment for any side effects.
Participants will then be followed every 12 weeks to check for the status of their disease up
to 12 months after the last subject on the trial has the last dose of study drug, or the
sponsor discontinues the study, whichever occurs first.
A Randomized Phase II Study of Regorafenib Followed by Anti-EGFR Monoclonal Antibody Therapy Versus the Reverse Sequencing for Metastatic Colorectal Cancer Patients Previously Treated With Fluoropyrimidine, Oxaliplatin and Irinotecan (REVERCE II)
PRIMARY OBJECTIVE:
I. To compare the overall survival between evaluable patients who were randomized to receive
regorafenib followed by anti-EGFR monoclonal antibody therapy compared to those that receive
anti-EGFR monoclonal antibody followed by regorafenib.
SECONDARY OBJECTIVES:
I. To compare the first progression free survival (PFS1) of patients between evaluable
patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody
therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib
II. To compare the second progression free survival (PFS2) of patients between evaluable
patients who were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody
therapy compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.
III. To compare the sequential treatment progression free survival (stPFS) of patients
between evaluable patients who were randomized to receive regorafenib followed by anti-EGFR
monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody
followed by regorafenib.
IV. To assess the frequency and severity of adverse events between evaluable patients who
were randomized to receive regorafenib followed by anti-EGFR monoclonal antibody therapy
compared to those that receive anti-EGFR monoclonal antibody followed by regorafenib.
V. To compare the objective response rate (ORR), while on initial treatment, between
evaluable patients who were randomized to receive regorafenib followed by anti-EGFR
monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal antibody
followed by regorafenib VI. To compare the objective response rate (ORR), while on sequential
treatment, between evaluable patients who were randomized to receive regorafenib followed by
anti-EGFR monoclonal antibody therapy compared to those that receive anti-EGFR monoclonal
antibody prior to regorafenib.
CORRELATIVE RESEARCH OBJECTIVES:
I. To assess plasma pharmacodynamics biomarkers of response and resistance to therapy.
II. To explore any correlation between tissue and blood based biomarkers and clinical
outcomes.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive regorafenib orally (PO) once daily (QD) on days 1-21. Cycles repeat
every 28 days in the absence of disease progression or unacceptable toxicity. Per the
treating physician's discretion, patients who experience disease progression may initiate a
treatment regimen consisting of cetuximab or panitumumab intravenously (IV) over 30-90
minutes on days 1 and 15. Patients may also receive irinotecan IV on days 1 and 15 as
determined by the study doctor. Cycles repeat every 28 days until disease progression or
unacceptable toxicity.
ARM B: Patients receive cetuximab or panitumumab IV over 30-90 minutes on days 1 and 15.
Patients may also receive irinotecan IV on days 1 and 15 as determined by the study doctor.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Per the treating physician's discretion, patients who experience disease progression may
initiate a treatment regimen consisting of regorafenib PO QD on days 1-21. Cycles repeat
every 28 days until disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, and then every 3
months for up to 3 years after randomization.
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
15-19 (5/2)
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
Myeloma).
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
available).
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