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A Phase 1/2 Study of CBX-12 in Children, Adolescents, or Young Adults With Solid Tumors That Have Come Back After Treatment or Are Difficult to Treat

ConditionsRecurrent Childhood Ewing SarcomaRecurrent Childhood Malignant Solid NeoplasmRecurrent Childhood RhabdomyosarcomaRecurrent Ewing SarcomaRecurrent Extracranial Malignant Solid NeoplasmRecurrent RhabdomyosarcomaRefractory Childhood Ewing SarcomaRefractory Childhood Malignant Solid NeoplasmRefractory Childhood RhabdomyosarcomaRefractory Ewing SarcomaRefractory Extracranial Malignant Solid NeoplasmRefractory Rhabdomyosarcoma
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12-30
SponsorChildren's Oncology Group

About this trial

This phase I/II trial tests the safety, best dose, and effectiveness of CBX-12 in the treatment of pediatric patients (ages 12 months to 30 years) with rhabdomyosarcoma, Ewing sarcoma, or other extracranial solid tumors that have come back after a period of improvement (relapsed) or that do not respond to treatment (refractory). CBX-12 is a conjugate drug made of a peptide linked to a drug called exatecan. Upon administration, the peptide portion of CBX-12 gets inserted into the membrane of tumor cells and then exatecan is released into the tumor cells. Exatecan inhibits deoxyribonucleic acid replication in tumors cells, leading to tumor cell death. CBX-12 may be a safe and effective treatment option for pediatric patients with relapsed or refractory rhabdomyosarcoma, Ewing sarcoma, or other solid tumors.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

PART A: Patients between ≥ 12 months and < 21 years of age

PART B: Patients between ≥ 12 months and ≤ 30 years of age

Patients with recurrent or refractory extracranial solid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse

Part A: Patients with relapsed or refractory extracranial solid tumors, excluding central nervous system (CNS)

Disqualifiers

Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of reproductive potential should use effective contraception and should not breastfeed during treatment and for at least 6 months after the last dose of CBX-12. Male patients treated with CBX-12 should use effective contraception and avoid fathering a child during and up to 4 months after treatment

Patients who are currently receiving another investigational drug are not eligible

Patients who are currently receiving other anti-cancer agents are not eligible

Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial

Trial design

Design model

Single group

Treatments tested in this trial

  • Archive Sample Retrieval

    Procedure/Surgery

    Ancillary studies

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of bone marrow and blood samples

  • pH Low Insertion Peptide-exatecan Conjugate CBX-12

    Drug

    Given IV

  • Radiologic Imaging Procedure

    Procedure/Surgery

    Undergo radiologic imaging

Treatment groups

79 Participants
are divided into 1 treatment group
Group A: Treatment (CBX-12)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Maximum tolerated dose (MTD) (part A phase 1 dose escalation)

The MTD will be defined as the maximum dose level at which fewer than one-third of dose limiting toxicity (DLT)-evaluable patients experience a cycle 1 DLT.

Time frame
During cycle 1 of part A (dose escalation phase; cycle length = 21 days)
2

Recommended phase 2 dose (part A phase 1 dose escalation)

Time frame
During cycle 1 of part A (dose escalation phase; cycle length = 21 days)
3

Incidence of adverse events (part A phase 1 dose escalation)

A descriptive summary of all toxicities will be reported. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.

Time frame
During cycle 1 of part A (dose escalation phase; cycle length = 21 days)
4

Pharmacokinetics (part A phase 1 dose escalation)

A descriptive analysis of pharmacokinetic parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The pharmacokinetic parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

Time frame
During cycle 1 of part A (dose escalation phase; cycle length = 21 days)

Secondary outcomes

1

Objective response rate (part A phase 1 dose escalation)

A responder is defined as a patient who achieves a best confirmed response of partial response or complete response on the study. Response is defined relative to baseline disease. For each cohort, response rates will be estimated by the uniformly minimum variance unbiased estimate, p-value, and 93% one-sided confidence interval consistent with a two-stage design.

Time frame
During part A phase 1 dose escalation

Other outcomes

1

Effect of tumor expression of SLFN11 and/or CAIX on pH low insertion peptide-exatecan conjugate CBX-12 (CBX-12) activity

Will evaluate whether the activity of CBX-12 is influenced tumor expression of SLFN11 and/or CAIX. A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature.

Time frame
Up to 60 months
2

Effect of homologous recombinant deficient (HRD) or deoxyribonucleic acid (DNA) repair deficient profile on CBX-12 activity

Will evaluate whether the activity of CBX-12 is associated with and HRD or DNA repair deficient profile, measured by whole exome sequencing. A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature.

Time frame
Up to 60 months
3

Effect of metabolic profile on CBX-12 activity

Will evaluate whether the activity of CBX-12 is influenced by the tumor metabolic profile. A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature.

Time frame
Up to 60 months
4

pH2AX

Will evaluate the biologic activity of CBX-12 by immunohistochemical assessments of pH2AX. A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature.

Time frame
Before and after treatment

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Children's Oncology Group

Lead sponsor

Source ClinicalTrials.gov

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