RecruitingMetastatic Malignant Solid NeoplasmUnresectable Malignant Solid Neoplasm

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

Eligible age

18+ yrs

Accepts

All genders

Locations

10 states

Healthy volunteers

See if you qualify for this study

Answer a few quick questions about your location and health. Takes about a minute.

Check my eligibility →

About this study

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.

Sponsor: National Cancer Institute (NCI)

You may qualify if…

✓ 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

You may not qualify if…

✕ 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