An Open-label, Navigational Investigation of Profile-related Evidence Determining Individualized Cancer Therapy for Patients With Aggressive Malignancies and Poor Prognoses
Overview
- Phase
- Phase 1
- Intervention
- Targeted agent
- Conditions
- Cancer
- Sponsor
- Medical College of Wisconsin
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- Matched treatment
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief 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.
Investigators
Hui-Zi Chen, MD, PhD
Assistant Professor
Medical College of Wisconsin
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years.
- •Patient with aggressive solid malignancy must meet at least one of the following:
- •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
- •Refused standard therapies, OR
- •Cancer of unknown primary or a rare tumor (i.e., fewer than 4 cases per 100,000 per year) with no approved therapies.
- •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.
- •Patient must have at least one of the following for a diagnosis/disease status:
- •Unresectable disease, as determined by a disease-appropriate multidisciplinary tumor board.
- •Medically unfit for surgical resection but with an expected survival of \> three months.
- •Localized disease and are eligible for neoadjuvant treatment.
Exclusion Criteria
- •A potential study subject who meets any of the following exclusion criteria is ineligible to participate in the study.
- •Two oncologists disagree on prognosis or resectability.
- •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).
- •Is pregnant or breastfeeding or any patient with childbearing potential not using adequate pregnancy prevention.
- •Whole brain radiation or stereotactic radiotherapy to CNS metastases within 14 days prior to start of study treatment.
Arms & Interventions
Group 1: Targeted agent
Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 1 subjects will comprise treatment naïve subjects with localized disease and (i) are eligible for neoadjuvant treatment, (ii) have unresectable disease, or (iii) are medically unfit for surgical resection.
Intervention: Targeted agent
Group 1: Standard of care agent
Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 1 subjects will comprise treatment naïve subjects with localized disease and (i) are eligible for neoadjuvant treatment, (ii) have unresectable disease, or (iii) are medically unfit for surgical resection.
Intervention: Standard of care agent
Group 2: Targeted agent
Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 2 will comprise treatment naïve subjects with metastatic disease.
Intervention: Targeted agent
Group 2: Standard of care agent
Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 2 will comprise treatment naïve subjects with metastatic disease.
Intervention: Standard of care agent
Group 3: Targeted agent
Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 3 will comprise subjects with metastatic or unresectable disease who have received at least one prior systemic therapy, whether matched or unmatched.
Intervention: Targeted agent
Group 3: Standard of care agent
Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 3 will comprise subjects with metastatic or unresectable disease who have received at least one prior systemic therapy, whether matched or unmatched.
Intervention: Standard of care agent
Outcomes
Primary Outcomes
Matched treatment
Time Frame: 8 months
The number of subjects who receive matched treatment based on multiomic profiling analysis and MTB recommendations.
Secondary Outcomes
- Actionable alterations(8 months)
- MTB recommended treatment(8 months)