Old antibiotic, new hope: novobiocin targets Cancer's weak DNA repair
NCT ID NCT05687110
First seen Jun 26, 2026 · Last updated Aug 04, 2026 · Updated 5 times
Summary
This early-phase trial tests an antibiotic called novobiocin in people with advanced solid tumors that have specific DNA repair mutations (like BRCA). The drug blocks a protein cancer cells use to fix their damaged DNA, which may cause them to die. The study aims to find the safest dose and see if it can shrink or stabilize tumors.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- Novobiocin (an antibiotic that blocks a DNA repair protein)
- What this could lead to
- If it works, this could point toward a new treatment option for people with certain DNA repair-deficient cancers that have stopped responding to standard therapies.
- What could go wrong
- This is a very early, small Phase 1 trial focused on safety and dosing, not yet on effectiveness. The drug may not shrink tumors or may cause side effects.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1
The first testing in people. Mainly checks safety and dose, usually in a small group.
- Participants
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About 43 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Jul 2023
- Expected to finish
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Jul 2028
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
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
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The study's own enquiry address
This study publishes an address for enquiries. See it below .
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The places running it
18 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Show contact details
Enter your email to view the contact information for this study.
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Locations
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Beth Israel Deaconess Medical Center
RECRUITINGBoston, Massachusetts, 02215, United States
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City of Hope Comprehensive Cancer Center
RECRUITINGDuarte, California, 91010, United States
Contact Email: •••••@•••••
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Dana-Farber Cancer Institute
RECRUITINGBoston, Massachusetts, 02215, United States
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Fred Hutchinson Cancer Center
RECRUITINGSeattle, Washington, 98109, United States
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Huntsman Cancer Institute/University of Utah
RECRUITINGSalt Lake City, Utah, 84112, United States
Contact Email: •••••@•••••
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Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITINGNew York, New York, 10016, United States
Contact Email: •••••@•••••
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Los Angeles General Medical Center
RECRUITINGLos Angeles, California, 90033, United States
Contact Email: •••••@•••••
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NYU Langone Hospital - Long Island
RECRUITINGMineola, New York, 11501, United States
Contact Email: •••••@•••••
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National Cancer Institute Developmental Therapeutics Clinic
RECRUITINGBethesda, Maryland, 20892, United States
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National Institutes of Health Clinical Center
ACTIVE_NOT_RECRUITINGBethesda, Maryland, 20892, United States
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Ohio State University Comprehensive Cancer Center
RECRUITINGColumbus, Ohio, 43210, United States
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UC Irvine Health/Chao Family Comprehensive Cancer Center
ACTIVE_NOT_RECRUITINGOrange, California, 92868, United States
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UC San Diego Medical Center - Hillcrest
RECRUITINGSan Diego, California, 92103, United States
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UC San Diego Moores Cancer Center
RECRUITINGLa Jolla, California, 92093, United States
Contact Email: •••••@•••••
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UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
ACTIVE_NOT_RECRUITINGIrvine, California, 92612, United States
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USC / Norris Comprehensive Cancer Center
RECRUITINGLos Angeles, California, 90033, United States
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University Health Network-Princess Margaret Hospital
ACTIVE_NOT_RECRUITINGToronto, Ontario, M5G 2M9, Canada
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University of California Davis Comprehensive Cancer Center
ACTIVE_NOT_RECRUITINGSacramento, California, 95817, United States
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University of Chicago Comprehensive Cancer Center
RECRUITINGChicago, Illinois, 60637, United States
Contact Email: •••••@•••••
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University of Oklahoma Health Sciences Center
RECRUITINGOklahoma City, Oklahoma, 73104, United States
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University of Washington Medical Center - Montlake
RECRUITINGSeattle, Washington, 98195, United States
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University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
RECRUITINGMadison, Wisconsin, 53718, United States
Contact Email: •••••@•••••
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University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITINGMadison, Wisconsin, 53792, United States
Contact Email: •••••@•••••
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