Novobiocin for Tumors with DNA Repair Gene Alterations
This study is testing a medication called novobiocin in people with advanced solid tumors that have specific changes (mutations) in their DNA repair genes. Novobiocin is an antibiotic that works by blocking a protein involved in DNA repair, which can cause cancer cells with damaged DNA to die. The main goal is to find the safest and most effective dose of novobiocin. Researchers will also look at how well novobiocin shrinks or stabilizes tumors. You might be able to join if you have a metastatic (spread) or unresectable (cannot be removed by surgery) solid tumor with certain DNA repair gene mutations, such as in BRCA1/2 or ATM, and standard treatments are no longer working.
- Study design
- This is an interventional study with a planned enrollment of 43 participants. It aims to determine the maximum tolerated dose and recommended phase 2 dose of novobiocin.
- What's involved
- You would undergo tumor biopsies, blood sample collections, and medical imaging scans. Novobiocin will be given by mouth (PO) on a schedule of 5 days on and 2 days off.
- Compensation
- Not stated in the trial record.
- Follow-up
- The maximum tolerated dose and recommended phase 2 dose will be measured for up to 2 years.
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NCT05687110
Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes
Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~43 participants
Updated 2026-08-03 on ClinicalTrials.gov
What's tested:Biopsy ProcedureBiospecimen CollectionDiagnostic Imaging TestingNovobiocin Sodium
At a glance
Recruiting sites
18 of 23 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum tolerated dose (MTD) and recommended phase 2 dose of continuous novobiocin administration
Measured over Up to 2 years
Conditions
Where it's being run
23 sites across 11 statesCalifornia8
Maryland2
Massachusetts2
New York2
Washington2
Wisconsin2
Illinois1
Ohio1
Study leadership
- Geoffrey I Shapiro · PRINCIPAL_INVESTIGATOR · Dana-Farber - Harvard Cancer Center LAO
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
What this trial measures
- Maximum tolerated dose (MTD) and recommended phase 2 dose of continuous novobiocin administrationUp to 2 years
The MTD will be identified as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. Standard hematological and non-hematologic parameters, scored using Common Terminology Criteria for Adverse Events version 5.0, will be used to define dose limiting toxicity.