Trial Title:
Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness
NCT ID:
NCT05691491
Condition:
Advanced Malignant Solid Neoplasm
Advanced Microsatellite Stable Colorectal Carcinoma
Hematopoietic and Lymphatic System Neoplasm
Metastatic Malignant Solid Neoplasm
Metastatic Microsatellite Stable Colorectal Carcinoma
Stage III Colorectal Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Conditions: Official terms:
Carcinoma
Neoplasms
Colorectal Neoplasms
Temozolomide
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (tuvusertib, temozolomide)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Treatment (tuvusertib, temozolomide)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (tuvusertib, temozolomide)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (tuvusertib, temozolomide)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Given orally (PO)
Arm group label:
Treatment (tuvusertib, temozolomide)
Other name:
CCRG-81045
Other name:
Gliotem
Other name:
Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
Other name:
M & B 39831
Other name:
M and B 39831
Other name:
Methazolastone
Other name:
RP-46161
Other name:
SCH 52365
Other name:
Temcad
Other name:
Temizole
Other name:
Temodal
Other name:
Temodar
Other name:
Temomedac
Other name:
TMZ
Intervention type:
Drug
Intervention name:
Tuvusertib
Description:
Given PO
Arm group label:
Treatment (tuvusertib, temozolomide)
Other name:
ATR Kinase Inhibitor M1774
Other name:
M 1774
Other name:
M-1774
Other name:
M1774
Summary:
This phase I/II trial studies the side effects and best dose of temozolomide and M1774
and how well they works in treating patients with cancer that has spread from where it
first started (primary site) to other places in the body (metastatic) and may have spread
to nearby tissue, lymph nodes, or distant parts of the body (advanced). Temozolomide is
in a class of medications called alkylating agents. It works by damaging the cell's
deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth.
M1774 may stop the growth of cancer cells by blocking some of the enzymes needed for cell
growth. Adding M1774 to temozolomide may shrink or stabilize cancer for longer than
temozolomide alone.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose of the combination of temozolomide (TMZ) and
tuvusertib (M1774).
SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity. II. To determine the overall response rate.
III. To estimate progression free survival. IV. To estimate overall survival. V. To
determine the recommended phase 2 dose of the combination of TMZ and M1774.
EXPLORATORY OBJECTIVES:
I. Correlate MGMT promoter hypermethylation, MGMT expression and tumor-infiltrating
lymphocytes (TILs) with efficacy endpoints of response rate, progression free survival,
and overall survival.
II. Assess pre and post treatment tumor biopsies for changes in tumor mutational burden,
tumor associated neo-antigens and microsatellite status by whole exome sequencing.
III. Measure changes in peripheral blood mononuclear cell populations with treatment.
IV. Assess liquid biopsies by circulating tumor (ct)DNA for changes in tumor mutational
burden and microsatellite status by whole exome sequencing.
OUTLINE: This is a phase I, dose-escalation study of temozolomide and tuvusertib followed
by a phase II study.
Patients receive tuvusertib orally (PO) once daily (QD) on days 1-7 and temozolomide PO
QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease
progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and
magnetic resonance imaging (MRI) as well as collection of blood samples throughout the
trial. Patients also undergo a biopsy at baseline and may undergo one on study and/or
time of progression.
After completion of study treatment, patients are followed up at 4 weeks, and then every
3 months for up to 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed diagnosis of metastatic
advanced cancer.
- In dose escalation, any solid tumor patients with either O6-methylguanine DNA
methyltransferase (MGMT) promoter hypermethylation positivity on testing /
pre-screening of archival tissue OR an extracranial solid tumor where TMZ is
considered a standard of care per National Comprehensive Cancer Network (NCCN)
guidelines (neuroendocrine tumor, small cell lung cancer, melanoma or soft tissue
sarcoma). The tumor lesion must be safely accessible to a mandatory biopsy. Patients
with MGMT promoter hypermethylated colorectal cancer must be mismatch repair
proficient / microsatellite stable.
- In phase 2, only patients with mismatch repair proficient / microsatellite stable
colorectal cancer that have MGMT promoter hypermethylation positivity on
pre-screening of archival tissue will be eligible.
- In dose escalation, patients must have progressed after treatment with all available
therapies including immunotherapies for metastatic disease that are known to confer
clinical benefit, or are intolerant to treatment, or refuse standard treatment.
Patients may not have previously received temozolomide or an ataxia telangiectasia
and rad3-related (ATR) inhibitor.
- For patients with mismatch repair proficient / microsatellite stable colorectal
cancer in the phase 2 portion, patients must have received prior therapy with 1 or
more systemic therapies in the metastatic setting that includes 5-fluorouracil,
irinotecan, and oxaliplatin. Patients with microsatellite stable colorectal cancer
(mCRC) need to have had exposure, unless contraindicated, to all 3 of oxaliplatin,
irinotecan, and fluoropyrimidine (FP).
The use of 5-fluorouracil and oxaliplatin in the adjuvant setting is acceptable, provided
the development of metastatic disease was less than 6 months after the completion of
adjuvant therapy.
Patients with a prior hypersensitivity reaction to oxaliplatin in the adjuvant setting do
not require retreatment in the metastatic setting.
- Age >=18 years. Because no dosing or adverse event data are currently available on
the use of M1774 in combination with temozolomide in patients < 18 years of age,
children are excluded from this study.
- Measurable disease on CT and/or MRI per Response Evaluation Criteria in Solid Tumors
(RECIST) version (v)1.1 criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (or Karnofsky >=
60%).
- Hemoglobin >=10 g/dL (No blood transfusions are allowed within 14 days of cycle 1
day 1 [C1D1]).
- White blood cells (WBC) > 3 x 10^9/L.
- Absolute neutrophil count >= 1,500/mcL.
- Platelets >= 100,000/mcL.
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN).
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine-aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT])
=< 3 x institutional ULN except for when liver metastases are present, in which case
they must be =< 5 x institutional ULN.
- Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2.
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression for 4
weeks.
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better.
- The effects of M1774 on the developing human fetus are unknown. For this reason and
because ATR inhibitors agents as well as other therapeutic agents used in this trial
are known to be teratogenic, women of child-bearing potential must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
prior to study entry, for the duration of study participation, and 6 months after
completion of M1774 administration. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately. Men treated or enrolled on this protocol must
also agree to use adequate contraception prior to the study, for the duration of
study participation, and 3 months after completion of M1774 administration.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia and
neuropathy, which may be =< grade 2.
- History of allergic reactions or hypersensitivity attributed to compounds of similar
chemical or biologic composition to M1774 or temozolomide, including dacarbazine.
- Patients with uncontrolled intercurrent illness.
- Pregnant women are excluded from this study because M1774 is an ATR inhibiting agent
with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with M1774 breastfeeding should be discontinued if the
mother is treated with M1774. These potential risks also apply to temozolomide.
- Patients with a prior history of ataxia telangiectasia.
- Patients who are not able to swallow orally administered medication or have
gastrointestinal disorders likely to interfere with absorption of the study
medication.
- Patients who cannot discontinue proton-pump inhibitors (PPIs) while taking M1774.
H-2 receptor antagonists are allowed but should not be taken within 12 hours before
or 2 hours after M1774. Antacids are also allowed, but should not be taken 2 hours
before 2 hours after M1774.
- Extensive RT involving greater than 30% of the bone marrow is not permitted during
the study.
- A Fridericia's correction formula (QTcF) > 480 ms is exclusionary given the
potential for QT.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UC San Diego Moores Cancer Center
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
858-822-5354
Email:
cancercto@ucsd.edu
Investigator:
Last name:
Shumei Kato
Email:
Principal Investigator
Facility:
Name:
Yale University
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
203-785-5702
Email:
canceranswers@yale.edu
Investigator:
Last name:
Michael Cecchini
Email:
Principal Investigator
Facility:
Name:
Smilow Cancer Hospital Care Center-Trumbull
Address:
City:
Trumbull
Zip:
06611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
203-785-5702
Email:
canceranswers@yale.edu
Investigator:
Last name:
Michael Cecchini
Email:
Principal Investigator
Facility:
Name:
Memorial Hospital East
Address:
City:
Shiloh
Zip:
62269
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
314-747-9912
Email:
dschwab@wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
University of Kansas Clinical Research Center
Address:
City:
Fairway
Zip:
66205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
University of Kansas Cancer Center
Address:
City:
Kansas City
Zip:
66160
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
University of Kansas Cancer Center-Overland Park
Address:
City:
Overland Park
Zip:
66210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
University of Kansas Hospital-Indian Creek Campus
Address:
City:
Overland Park
Zip:
66211
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
University of Kansas Hospital-Westwood Cancer Center
Address:
City:
Westwood
Zip:
66205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at West County Hospital
Address:
City:
Creve Coeur
Zip:
63141
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
University of Kansas Cancer Center - North
Address:
City:
Kansas City
Zip:
64154
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
University of Kansas Cancer Center - Lee's Summit
Address:
City:
Lee's Summit
Zip:
64064
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
University of Kansas Cancer Center at North Kansas City Hospital
Address:
City:
North Kansas City
Zip:
64116
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Raed Al-Rajabi
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center-South County
Address:
City:
Saint Louis
Zip:
63129
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Christian Hospital
Address:
City:
Saint Louis
Zip:
63136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Saint Peters Hospital
Address:
City:
Saint Peters
Zip:
63376
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
Abdul Rafeh Naqash
Email:
Principal Investigator
Facility:
Name:
University of Pittsburgh Cancer Institute (UPCI)
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
412-647-8073
Investigator:
Last name:
Janie Y. Zhang
Email:
Principal Investigator
Start date:
September 28, 2023
Completion date:
January 31, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05691491
