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Protocol Details

A Phase 1 Study of the Polymerase Theta (POL-Theta) Inhibitor Novobiocin in BRCA-mutant and Other DNA Damage Repair-Deficient Solid Tumors

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


polymerase theta;
PARP inhibitor resistance

Recruitment Keyword(s)




Investigational Drug(s)

Novobiocin Sodium

Investigational Device(s)



Drug: novobiocin sodium

Supporting Site

National Cancer Institute


Some cancers have mutated genes that make it more difficult for the cells to repair themselves. These include some cancers of the ovary, breast, prostate, and pancreas. These mutated genes make these tumors difficult to treat.


To test a drug (novobiocin) in people with solid tumors that have certain gene mutations.


People aged 18 years and older with a solid tumor that has a known genetic mutation linked to cancer.


Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. Their ability to perform everyday tasks will be assessed. They will have a biopsy: A sample of tissue will be cut from their tumor. (Samples from a recent biopsy may be used instead.)

Novobiocin is a pill taken by mouth. Participants will take the pill twice a day, every day, in 28-day cycles.

Participants will have follow-up visits once a week during the first cycle. After that, the visits will be at longer intervals. They will have blood tests at every visit. They will be asked about any side effects they may be having. The biopsy and other tests will also be repeated at different times.

Participants may remain in the study as long as the drug is helping them. Follow-up visits may continue every 3 to 6 months for up to 2 years after treatment ends.

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-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.

-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-naive (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 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.

-ECOG performance status <=2 (Karnofsky >=60%).

-Patients must have adequate organ and marrow function as defined below:

--absolute neutrophil count >= 1,500/mcL

--leukocytes >= 3,000/mcL

--platelets >= 100,000/mcL

--total bilirubin <= 1.5 (SqrRoot) institutional upper limit of normal (ULN)

--AST(SGOT)/ALT(SGPT) <= 3 (SqrRoot) institutional ULN

--glomerular filtration rate (GFR) >= 60 mL/min (via the CKD-EPI glomerular filtration rate estimation)

--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 POL-Theta inhibitor agents have the potential to be teratogenic, women of childbearing 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.


-Patients who have had chemotherapy or radiotherapy within 4 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 receiving concurrent medications associated with a risk of 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 with uncontrolled intercurrent illness.

-Pregnant women are excluded from this study because novobiocin is a POLQTheta 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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Not Provided

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Principal Investigator

Referral Contact

For more information:

Alice P. Chen, M.D.
National Cancer Institute (NCI)
(240) 781-3320

Nancy Moore, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 8D53
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6045

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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