Investigation of Profile-related Evidence Determining Individualized Cancer Therapy for Patients With Aggressive Malignancies and Poor Prognoses

NCT05674825 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PRO00045600
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer

Keywords

metastatic disease; unresectable disease; advanced malignancies; molecular profile

Outcome Measures

Primary Outcomes (1)

• Matched treatment

  The number of subjects who receive matched treatment based on multiomic profiling analysis and MTB recommendations.

  8 months

Secondary Outcomes (2)

• Actionable alterations

  8 months

• MTB recommended treatment

  8 months

Study Arms (6)

Group 1: Targeted agent

EXPERIMENTAL

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.

Drug: Targeted agent

Group 1: Standard of care agent

EXPERIMENTAL

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.

Drug: Standard of care agent

Group 2: Targeted agent

EXPERIMENTAL

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.

Drug: Targeted agent

Group 2: Standard of care agent

EXPERIMENTAL

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.

Drug: Standard of care agent

Group 3: Targeted agent

EXPERIMENTAL

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.

Drug: Targeted agent

Group 3: Standard of care agent

EXPERIMENTAL

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.

Drug: Standard of care agent

Interventions

Targeted agent DRUG

The Molecular Tumor Board (MTB) will suggest molecularly targeted "matched" treatment.

Group 1: Targeted agent; Group 2: Targeted agent; Group 3: Targeted agent

Standard of care agent DRUG

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).

Group 1: Standard of care agent; Group 2: Standard of care agent; Group 3: Standard of care agent

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Metastatic disease.
• 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.
• Patient is either:
• Treatment naïve for their newly diagnosed malignancy (for enrollment to Groups 1 or 2), or
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hui-Zi Chen, MD, PhD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Razelle Kurzrock, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 23, 2022
• First Posted: January 9, 2023
• Study Start: December 21, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): January 1, 2031
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)