Recruiting

Phase 1

NovobiocinStudying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05687110

Conditions

Metastatic Malignant Solid Neoplasm

Unresectable Malignant Solid Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Diagnostic Imaging Testing

Novobiocin Sodium

Study Details

Brief summary:

This phase I trial tests the safety, side effects, and best dose of novobiocin in treating cancer patients with alterations in deoxyribonucleic acid (DNA) repair genes. Novobiocin is an antibiotic that blocks the activity of a protein called DNA polymerase theta, which helps repair DNA that has become damaged as cells grow and divide. Cancer cells that cannot repair their damaged DNA die. This medication may help shrink or stabilize cancer with a mutation in DNA repair genes.

Conditions

Metastatic Malignant Solid Neoplasm

Unresectable Malignant Solid Neoplasm

Study ID

NCT05687110

Start date

Jul 6, 2023

Status verified date

Jul, 2026

Completion date

Jul 1, 2028

Anticipated

Primary completion date

Jul 1, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patients must have histologically confirmed solid tumor with a known pathogenic mutation in BRCA1/2, PALB2, RAD51C, RAD51D, ATM, BARD1, BLM, BRIP1, CDK12, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN (NBS1), RAD50 and RAD51B as confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified method. Patients with alterations defined only by germline testing are eligible. Other qualifying HRD alterations may be considered if approved by the principal investigator and the Cancer Therapy Evaluation Program (CTEP) monitor
Any number of prior therapy regimens is allowed
Patients with cancers for which PARP inhibitors have been approved as standard-of-care must have received a PARP inhibitor prior to enrollment on this study. Other patients may be either PARP inhibitor-naïve (i.e., never have received a PARP inhibitor) or have disease that is PARP inhibitor-resistant (i.e., disease that has progressed radiologically based on Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 while receiving any PARP inhibitor)
Age >= 18 years. Because no dosing or adverse event data are currently available on the use of novobiocin in patients < 18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group Performance (ECOG) performance status =< 2 (Karnofsky >= 60%)
Absolute neutrophil count >= 1,500/mcL
Leukocytes >= 3,000/mcL
Platelets >= 100,000/mcL
Total bilirubin =< 1.5 × institutional upper limit of normal (ULN)
Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine transferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =< 1.5 × institutional ULN
Glomerular filtration rate (GFR) >= 60 mL/min (via the chronic kidney disease epidemiology \[CKD-EPI\] glomerular filtration rate estimation)
Fridericia's formula-corrected QT interval (QTcF) =< 480 ms
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, stable and off steroids for 1 month
Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the patient is asymptomatic and the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
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 should be New York Heart Association Functional Classification of class 2B or better
Patients must have tumors amenable to biopsies, and be willing to undergo biopsies at two time points (pre- and on-treatment)
The effects of novobiocin on the developing human fetus are unknown. For this reason and because polymerase theta (POLtheta) inhibitor agents have the potential to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of novobiocin administration. Effective contraception is defined as a method that achieves a failure rate of less than 1% per year when used consistently and correctly. (Note: Because of a concern for decreased effectiveness of estrogen-containing oral agents when given with novobiocin, barrier methods and abstinence are the preferred methods for contraception). 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
Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
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
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to novobiocin
Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4/5 are ineligible. Patients receiving any medications or substances that are known to be substrates of breast cancer resistance protein (BCRP/ABCG2) and/or organic anion transporting polypeptides (OATP1B1, OATP1B3 and OATP2B1) and/or organic anion transporters (OAT1 and OAT3) within 14 days prior to the first dose of study drug are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Patients using herbal/dietary supplements with known hepatotoxicity risk are ineligible
Patients receiving concurrent medications associated with a risk of corrected QT interval (QTc) prolongation and/or Torsades de Pointes are not allowed within 14 days of initiation of study treatment. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference such as CredibleMeds or Lexicomp. Drugs listed in the "drugs to avoid in CLQTS (congenital long QT syndrome)" and "known risk of TdP (torsade de pointes)" should be excluded. Granisetron is an acceptable antiemetic on this study. If a patient must take ondansetron, they may NOT take any other concomitant agents which might impact their QTc
Patients must have UGT1A1 testing at screening. Patients homozygous for A(TA)7TAA in the promoter region (also known as UGT1A1 \*28), homozygous for the G71R allele (also known as UGT1A1\*6), or with compound alterations of \*28 and \*6, are excluded as they are at risk for further reduction of UGT1A1 activity that may disrupt bilirubin clearance

UGT1A1 testing must address both \*28 and \*6 alterations
Patients with uncontrolled intercurrent illness. Additionally, patients with acute liver disease, poorly controlled liver disease, or cirrhosis are excluded
Patients with (known) active or poorly controlled alcohol use disorder are excluded
Pregnant women are excluded from this study because novobiocin is a POLtheta inhibitor 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 novobiocin, breastfeeding should be discontinued if the mother is treated with novobiocin

Study Design

Enrollment

43 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (novobiocin sodium)

Patients receive novobiocin sodium PO QD for 5 days in a row followed by 2 days off each week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, medical imaging scans, and collection of blood samples throughout the trial.

Interventions

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood sample collection

Diagnostic Imaging Testing

Undergo medical imaging scans

Novobiocin Sodium

Given PO

Primary outcome measure

Maximum tolerated dose (MTD) and recommended phase 2 dose of continuous novobiocin administration [ Time Frame: Up to 2 years ]

Central Contacts and Locations

Locations

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Site Public Contact

800-826-4673 becomingapatient@coh.org

Principal Investigator:

Sharonlin Bhardwaj

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093

Contacts

Site Public Contact

858-822-5354 cancercto@ucsd.edu

Principal Investigator:

Shumei Kato

Los Angeles General Medical Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451 uscnorrisinfo@med.usc.edu

Principal Investigator:

Varsha Tulpule

USC / Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451

Principal Investigator:

Varsha Tulpule

UC San Diego Medical Center - Hillcrest

Recruiting

San Diego, California, United States, 92103

Contacts

Site Public Contact

rhabbaba@health.ucsd.edu

Principal Investigator:

Shumei Kato

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Gini F. Fleming

National Cancer Institute Developmental Therapeutics Clinic

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

Site Public Contact

800-411-1222

Principal Investigator:

A P. Chen

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Site Public Contact

617-667-9925

Principal Investigator:

Gerburg M. Wulf

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Site Public Contact

877-442-3324

Principal Investigator:

Geoffrey I. Shapiro

NYU Langone Hospital - Long Island

Recruiting

Mineola, New York, United States, 11501

Contacts

Site Public Contact

212-263-4432 cancertrials@nyulangone.org

Principal Investigator:

Nancy Chan

Laura and Isaac Perlmutter Cancer Center at NYU Langone

Recruiting

New York, New York, United States, 10016

Contacts

Site Public Contact

CancerTrials@nyulangone.org

Principal Investigator:

Nancy Chan

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066 Jamesline@osumc.edu

Principal Investigator:

John L. Hays

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777 ou-clinical-trials@ouhsc.edu

Principal Investigator:

Debra L. Richardson

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100 cancerinfo@hci.utah.edu

Principal Investigator:

Vaia Florou

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Site Public Contact

800-804-8824

Principal Investigator:

Michael Schweizer

University of Washington Medical Center - Montlake

Recruiting

Seattle, Washington, United States, 98195

Contacts

Site Public Contact

800-804-8824

Principal Investigator:

Michael Schweizer

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Recruiting

Madison, Wisconsin, United States, 53718

Contacts

Site Public Contact

800-622-8922 clinicaltrials@cancer.wisc.edu

Principal Investigator:

Jeremy Kratz

University of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

Contacts

Site Public Contact

800-622-8922 clinicaltrials@cancer.wisc.edu

Principal Investigator:

Jeremy Kratz

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 3, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-03.