Trial Title:
Investigation of Profile-related Evidence Determining Individualized Cancer Therapy for Patients With Aggressive Malignancies and Poor Prognoses
NCT ID:
NCT05674825
Condition:
Cancer
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
metastatic disease
unresectable disease
advanced malignancies
molecular profile
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Targeted agent
Description:
The Molecular Tumor Board (MTB) will suggest molecularly targeted "matched" treatment.
Arm group label:
Group 1: Targeted agent
Arm group label:
Group 2: Targeted agent
Arm group label:
Group 3: Targeted agent
Intervention type:
Drug
Intervention name:
Standard of care agent
Description:
Subjects will receive treating physician's choice of traditional systemic therapy
treatment for their malignancy, defined by National Comprehensive Cancer Network (NCCN)
guidelines and/or tumor board recommendation(s).
Arm group label:
Group 1: Standard of care agent
Arm group label:
Group 2: Standard of care agent
Arm group label:
Group 3: Standard of care agent
Summary:
This is a prospective, open-label navigational investigation designed to evaluate the
feasibility of using molecular profile-based evidence to determine individualized cancer
therapy for patients with aggressive malignancies. This is a non-randomized,
histology-agnostic trial. Although there will be a case mix of histologies, the
investigators now know that individual histologies are composed of a heterogeneous mix of
molecular alterations. It is not clear whether one case mix is better or worse than
another. Thus, the investigators are testing a strategy of molecular matching that may
apply across different cancers.
Detailed description:
Eligible and consented patients, if not already performed, will have their tumor
tissues/blood molecularly profiled. Patients will be stratified into Group 1 (treatment
naïve, localized/unresectable/medically unfit for surgery), Group 2 (treatment naïve,
metastatic), and Group 3 (prior treated). Based on multiomic profiling, matched therapy,
if available, will be recommended by the Molecular Tumor Board. Patients who receive the
recommended matched therapy are designated to Arm A. Otherwise, those that receive the
unmatched therapy (i.e., treating physician's choice of therapy) or have no molecular
alterations are designated to Arm B. The study feasibility will be measured by the
ability to enroll patients, the acceptable turnaround time and the actionable information
obtained from multiomic profiling, and the viability of identifying and delivering the
matched therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years.
2. Patient with aggressive solid malignancy must meet at least one of the following:
1. Malignancy with ≥30% two-year cancer-associated mortality as estimated by the
treating oncologist and one of the study investigators and/or, where
appropriate, according to accepted data sets in the field (e.g., NCDB).
Diseases include but are not limited to: ampullary carcinoma, appendiceal
cancer, colorectal cancer (CRC), extrahepatic cholangiocarcinoma (EHCC),
esophageal adenocarcinoma, gallbladder cancer (GBCA) gastric adenocarcinoma,
head and neck cancer, hepatocellular carcinoma (HCC), intrahepatic
cholangiocarcinoma (IHCC), melanoma, non-KIT gastrointestinal stromal tumor
(GIST), non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic ductal
adenocarcinoma (PDAC), sarcoma (high-grade), small bowel adenocarcinoma
(including duodenal), triple-negative breast cancer (TNBC), urothelial cancer
2. Refused standard therapies, OR
3. Cancer of unknown primary or a rare tumor (i.e., fewer than 4 cases per 100,000
per year) with no approved therapies.
3. Patient with aggressive solid malignancy irrespective of two-year mortality who, in
the opinion of the investigator, has no treatment option expected to yield
significant clinical benefit.
4. Patient must have at least one of the following for a diagnosis/disease status:
1. Unresectable disease, as determined by a disease-appropriate multidisciplinary
tumor board.
2. Medically unfit for surgical resection but with an expected survival of > three
months.
3. Localized disease and are eligible for neoadjuvant treatment.
4. Metastatic disease.
5. Disease where no conventional therapy leads to a survival benefit > six months
in the respective cohort and line of therapy for which the patient is otherwise
eligible.
5. Patient is either:
1. Treatment naïve for their newly diagnosed malignancy (for enrollment to Groups
1 or 2), or
2. Status post one or more systemic therapy regimens, whether matched or unmatched
(for enrollment to Group 3). Note: There are no limitations on the number of
prior local therapies.
6. Patient must have measurable disease for malignancy: defined as at least one lesion
that can be accurately measured in at least one dimension (longest diameter to be
recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with
conventional techniques or as ≥10 mm with spiral CT scan, positron emission
tomography (PET) -CT, MRI, or calipers by clinical exam.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
8. New York Heart Association (NYHA) Functional Classification I-II
9. Adequate organ and marrow function as defined below:
1. Absolute neutrophil count ≥ 1.0 x 109/L
2. Platelet count ≥ 75 x 109/L
3. Total bilirubin ≤ 2.0 x institution's upper limit of normal (ULN)
4. Patients without underlying liver disease
• alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 x
institutional ULN
5. Serum creatinine ≤ 2.0 x institution's ULN or 24-hour creatinine clearance ≥ 30
ml/min
10. At the time of treatment, patient should be off other anti-tumor agents for at least
five half-lives of the agent or two weeks from the last day of treatment, whichever
is shorter to enroll in Group 3. Patient must not have been treated with anti-tumor
agents to enroll in Group 1 or Group 2. Patient must be off prior antibody therapy
for at least three half-lives before starting treatment.
11. Able to swallow and retain oral medication, if needed.
12. If actionable or appropriate molecular profiling has not already been performed,
patient must have or provide evaluable tissue and/or blood for molecular profiling.
This could be obtained during the standard of care tumor diagnosis or tumor staging
evaluation. Tissue and/or blood is to be procured based on clinical discretion and
discussion with the patient.
13. Pregnancy It is not known what effects matched therapy has on human pregnancy or
development of the embryo or fetus. Therefore, female subjects participating in this
study should avoid becoming pregnant, and male subjects should avoid impregnating a
female partner. Non-sterilized female subjects of reproductive age and male subjects
should use effective methods of contraception through defined periods during and
after study treatment as specified below.
Female participants: A female participant is eligible to participate if she is not
pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a female of childbearing potential (FCBP), defined as all female patients
that were not in post-menopause for at least one year or are surgically
sterile, OR
- An FCBP must have a negative serum pregnancy test and agree to use at least one
form of pregnancy prevention during the study for at least one month after
treatment discontinuation unless otherwise noted by the agent(s) USPI or IB,
which the FCBP must follow.
Male participants: A male participant, even if surgically sterilized (i.e., status
post-vasectomy), must use a form of barrier pregnancy prevention approved by the
investigator or treating physician during the study and for at least one month after
treatment discontinuation and refrain from donating sperm during this period unless
otherwise noted by the agent(s) U.S. Prescribing Information (USPI) or
investigator's brochure (IB), which the male participant must follow.
14. Ability to understand a written informed consent document, and the willingness to
sign it.
15. Patients presented at Molecular Tumor Board (MTB) up to two weeks prior to signing
consent are eligible to be treated on study based on the MTB recommendations and do
not need to be represented at MTB prior to starting therapy on trial (unless six
months elapsed between consent and start of study treatment).
Exclusion Criteria:
A potential study subject who meets any of the following exclusion criteria is ineligible
to participate in the study.
1. Two oncologists disagree on prognosis or resectability.
2. Severe or uncontrolled medical disorder that would, in the investigator's opinion,
confound study analyses of treatment response (i.e., uncontrolled diabetes, chronic
renal disease, chronic pulmonary disease or active, uncontrolled infection,
psychiatric illness/social situations that would limit compliance with study
requirements).
3. Is pregnant or breastfeeding or any patient with childbearing potential not using
adequate pregnancy prevention.
4. Whole brain radiation or stereotactic radiotherapy to CNS metastases within 14 days
prior to start of study treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Froedtert Hospital & the Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ben George, MD
Phone:
414-805-4600
Email:
bgeorge@mcw.edu
Start date:
December 21, 2022
Completion date:
January 2031
Lead sponsor:
Agency:
Medical College of Wisconsin
Agency class:
Other
Source:
Medical College of Wisconsin
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05674825
