Real-world Trial of Individualized Precision Oncology

NCT07346209 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 813379
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if drugs that are matched to tumor DNA mutations work to treat metastatic solid cancers in adults. The main questions it aims to answer are: Is tumor worsening delayed for a longer period of time if patients take drugs that match DNA mutations, compared to if they take standard of care drugs? Researchers will compare drugs matched to tumor DNA mutations to standard of care drugs to see if the matched drugs work better, and to see if tumor worsening can be delayed for longer the more DNA mutations the drugs target. Participants will: Take drugs matched to tumor DNA mutations or standard of care drugs based on the regular dosing schedule of the drugs. Visit the clinic every approximately 2 months for checkups and tumor imaging.

Conditions

Unresectable Carcinoma; Metastatic Cancer

Keywords

Precision medicine; Molecularly matched therapy; Tumor molecular alterations; Molecular Tumor Board

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Duration of time from randomization until objective tumor progression, clinical progression, treatment discontinuation due to inability to tolerate study therapy, or death from any cause.

  1 year

Study Arms (2)

Molecularly matched therapy

EXPERIMENTAL

Molecularly matched therapy based on tumor's molecular profile.

Drug: Molecularly matched therapy

Standard of care

ACTIVE COMPARATOR

Standard of care treatment.

Drug: Standard of care

Interventions

Molecularly matched therapy DRUG

Molecularly matched therapy, as identified by a molecular tumor board, to match molecular alterations/biomarkers found in the tumor or circulating tumor DNA.

Molecularly matched therapy

Standard of care DRUG

Standard of care therapy for the tumor type.

Standard of care

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Aged at least 18 years.
• Metastatic or unresectable solid cancers (all) with a 2-year cancer-associated mortality of ≥ 50%, or immediate prior progression free survival \< 4 months, or life expectancy between 6 and 16 months as determined at prescreening and/or enrollment due to cancer diagnosis.
• Previous treatment with up to 2 lines of cancer therapy before enrollment.
• Available results of tumor imaging performed within 4 weeks prior to randomization or eligible to obtain imaging as part of routine care. Note that patients are not eligible if their tumor imaging was performed more than 4 weeks before randomization, or if the imaging to be performed at screening is within 6 weeks of their previous imaging.
• Measurable disease by RECIST v 1.1 based on computed tomography, magnetic resonance imaging or positron emission tomography/computed tomography scan performed within 4 weeks prior to randomization.
• Case discussed by Molecular Tumor Board with consensus treatment recommendation(s).
• Presence of at least 1 tumor-derived molecular alteration/biomarker with a molecularly matched therapy option per Molecular Tumor Board recommendation.
• Molecular profile needs to be performed in tumor tissue or circulating tumor DNA collected in the 6 months before enrollment and analyzed by next generation sequencing, immunohistochemistry, and/or alternative technology in a Clinical Laboratory Improvement Amendments-accredited and College of American Pathologists-certified clinical laboratory.
• All prior pathology and molecular studies may be reviewed and considered by the Molecular Tumor Board.
• Molecularly matched therapy options are restricted to Food and Drug Administration-approved drugs.
• Eligible for at least 1 additional unmatched standard of care therapy.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• At the time of the screening/baseline visit, patients must be off prior antibody therapy for at least 3 half-lives, and other anti-tumor agents for at least 5 half-lives, or total 3 weeks from the last day of treatment, whichever is shortest.

You may not qualify if:

• Presence of very high tumor mutational burden as ≥ 20 mutations/megabase.
• Presence of a microsatellite instability-high as defined by the testing laboratory.
• Deficiency of mismatch repair genes: MLH1, MSH2, MSH6, or PMS2.
• Molecular Tumor Board treatment recommendation is a monotherapy with an immune checkpoint inhibitor.
• Molecular Tumor Board treatment recommendation is considered a standard of care regimen per NCCN guidelines (including treatments considered useful in certain circumstances).
• Example 1: Presence of BRAF V600E in lung cancer as the sole molecularly matched target is ineligible, given Food and Drug Administration approval of combination BRAFi/MEKi.
• Example 2: Presence of BRAF V600E and CDKN2A mutation in lung cancer is eligible, if the Molecular Tumor Board recommendation is the non-standard of care combination of BRAFi/MEKi + CDK4/6i
• Example 3: Presence of KRAS G12C in breast cancer is eligible as the use of KRAS inhibitors for this specific tumor type is not standard of care.
• Example 4: Presence of KRAS G12A mutation in colon cancer is eligible if the Molecular Tumor Board recommendation is for non-standard of care MEKi.
• Newly diagnosed symptomatic brain metastases requiring immediate treatment. Note that patients with asymptomatic or treated stable brain metastases not requiring steroids can be enrolled.
• Increase of Eastern Cooperative Oncology Group performance status of ≥ 1 point in the 30 days prior to enrollment.
• Pregnancy or lactation.
• Known allergic reactions to components of the therapy.
• Other conditions that preclude study participation at the discretion of the treating physician (e.g., organ or bone marrow dysfunction).
• Patient is in hospice care.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

La Jolla, California, 92093, United States

Location

Related Publications (3)

• Sicklick JK, Kato S, Okamura R, Patel H, Nikanjam M, Fanta PT, Hahn ME, De P, Williams C, Guido J, Solomon BM, McKay RR, Krie A, Boles SG, Ross JS, Lee JJ, Leyland-Jones B, Lippman SM, Kurzrock R. Molecular profiling of advanced malignancies guides first-line N-of-1 treatments in the I-PREDICT treatment-naive study. Genome Med. 2021 Oct 4;13(1):155. doi: 10.1186/s13073-021-00969-w.

  PMID: 34607609 BACKGROUND

• Sicklick JK, Kato S, Okamura R, Schwaederle M, Hahn ME, Williams CB, De P, Krie A, Piccioni DE, Miller VA, Ross JS, Benson A, Webster J, Stephens PJ, Lee JJ, Fanta PT, Lippman SM, Leyland-Jones B, Kurzrock R. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med. 2019 May;25(5):744-750. doi: 10.1038/s41591-019-0407-5. Epub 2019 Apr 22.

  PMID: 31011206 BACKGROUND

• Kato S, Kim KH, Lim HJ, Boichard A, Nikanjam M, Weihe E, Kuo DJ, Eskander RN, Goodman A, Galanina N, Fanta PT, Schwab RB, Shatsky R, Plaxe SC, Sharabi A, Stites E, Adashek JJ, Okamura R, Lee S, Lippman SM, Sicklick JK, Kurzrock R. Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy. Nat Commun. 2020 Oct 2;11(1):4965. doi: 10.1038/s41467-020-18613-3.

  PMID: 33009371 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Jason K. Sicklick, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason K. Sicklick, MD

CONTACT

(858) 822-5354; cancerCTO@health.ucsd.edu

Kim Rubin

CONTACT

(858) 822-5354; cancerCTO@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery and Pharmacology

Study Record Dates

• First Submitted: January 14, 2026
• First Posted: January 16, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)