Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)
About this trial
This phase I trial studies how well CBX-12 works in treating patients with solid tumors that have spread from where they first started (primary site) to started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or other places in the body (metastatic). CBX-12 works by binding to a protein called TOP1 that is present inside the cells. This allows CBX-12 to kill the cancer cells by damaging their DNA, resulting in cancer cell death. This trial is being done to find out if this approach is better or worse than the usual approach for advanced cancers.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have histologically confirmed solid tumors with metastatic disease that have progressed after >= 1 line of prior therapy
Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam)
Patients must have a tumor site amenable to biopsy
Age >= 18 years of age
Disqualifiers
Patients must have recovered from clinically-significant adverse-events of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia)
Eligibility of subjects receiving any medications or substances with the potential to affect the activity of CBX-12 or exatecan will be determined following review of their cases by the Principal Investigator
Patients who are receiving any other investigational agents
Patients taking medication known to prolong the QT interval, or receiving any medications or substances that are strong CYP3A4 or CYP1A2 inhibitors or inducers, and sensitive substrates of CYP3A or CYP2B6 with a narrow therapeutic index are ineligible, if they cannot be transferred to alternative medication. Patients on substrates of OATP1B1 and OATP1B3 should be excluded unless they can be transferred on alternative medication. 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
Trial design
Design model
Single group
Treatments tested in this trial
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT scan
pH Low Insertion Peptide-exatecan Conjugate CBX-12
DrugGiven IV
Treatment groups
35 Participants
are divided into 1 treatment groupGroup A: Treatment (CBX-12)Experimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Early Rad51/deoxyribonucleic acid (DNA) damage response (DDR)
Time frame
At cycle 1 day 2 (1 cycle = 28 days)2
Late Rad51/DDR response
Time frame
At cycle 3 day 1Secondary outcomes
1
Tumor TOP1 molecular response
Time frame
Up to 24-30 hours post-first dose2
DDR modulation and plasma exatecan concentrations
Association between tumor TOP1 and DDR modulation and plasma exatecan concentrations will be determined.
Time frame
Up to 2 years3
CD8 T cell infiltration and activation in tumor
The effects of CBX-12 on CD8 T cell infiltration and activation in tumor will be evaluated.
Time frame
Up to 2 yearsOther outcomes
1
Molecular markers of apoptosis
Non-parametric analyses will be used for these evaluations. In view of the exploratory nature of these analyses, any p-values reported will not be adjusted for multiple comparisons, and any such analyses will be stated carefully as being hypothesis-generating.
Time frame
Up to 2 years2
Genomic or gene expression characteristics in tumor that may be associated with sensitivity or resistance to CBX-12
Non-parametric analyses will be used for these evaluations. In view of the exploratory nature of these analyses, any p-values reported will not be adjusted for multiple comparisons, and any such analyses will be stated carefully as being hypothesis-generating.
Time frame
Up to 2 years3
Genomic alterations in circulating tumor DNA that may be associated with sensitivity or resistance to CBX-12
Non-parametric analyses will be used for these evaluations. In view of the exploratory nature of these analyses, any p-values reported will not be adjusted for multiple comparisons, and any such analyses will be stated carefully as being hypothesis-generating.
Time frame
Up to 2 years4
Changes in levels of any anti-drug antibodies
Non-parametric analyses will be used for these evaluations. In view of the exploratory nature of these analyses, any p-values reported will not be adjusted for multiple comparisons, and any such analyses will be stated carefully as being hypothesis-generating.
Time frame
Baseline up to 2 yearsSponsors and contacts
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Source ClinicalTrials.gov