DCV in the Treatment of Recurrence and Refractory Childhood Solid Tumors

December 25, 2019 updated by: Yizhuo Zhang, Sun Yat-sen University

Phase I Study of Pegylated Liposomal Doxorubicin Combined With Cyclophosphamide and Vincristine in Treatment Progress, Relapse, and Refractory Solid Tumors in Children

Doxorubicin is an anthracycline antibiotic that is part of the standard treatment for many pediatric malignancies, but its long-term cardiotoxicity cannot be ignored. Without affecting overall survival, in order to improve the quality of life of childhood tumor survivors and reduce cardiotoxicity, drugs with less cardiotoxicity should be selected; compared with ordinary doxorubicin, PEGylated doxorubicin (PLD ) The biggest advantage is the low cardiotoxicity.

PEGylated doxorubicin (Caelyx®) has undergone a Phase I dose climbing clinical trial in children with solid tumors. The drug is safe by testing PK. The results of Phase II clinical studies of Caelyx® in children with progressive soft tissue sarcoma show that the drug is safe. Domestically produced PEGylated doxorubicin has no data on childhood tumors in China. Therefore, we plan to conduct a phase I study in pediatric solid tumors of pegylated doxorubicin combined with cyclophosphamide, vincristine, relapsed, and refractory childhood solid tumors. Maximum tolerated dose and effectiveness of stellate in children with solid tumors, thus laying the foundation for future phase II / III clinical studies

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Purpose of Phase I:

the main purpose: To evaluate the safety of PLD in combination with cyclophosphamide, vincristine, regenerative, and refractory solid tumors in children, including dose absorption toxicity (DLT)

Secondary purpose:

  • determine the appropriate maximum tolerated dose (MTD) and /or PLD for further clinical studies in this patient population;
  • Describe the antitumor activity of PLD combined with cyclophosphamide and vincristine in children with advanced solid tumors or primary CNS tumors;

Exploratory purpose:

Effectiveness of PLD combined with cyclophosphamide and vincristine in treatment progress, relapse, and refractory solid tumors in children.

Study Type

Interventional

Enrollment (Anticipated)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 1) Age: 1-18 years;
  • 2) ECOG PS score: 0-1 points;
  • 3) Patients with solid tumors confirmed by histopathology in children;
  • 4) Patients who have progressed, relapsed, or are refractory after first-line treatment (there is no complete or partial response after recent treatment);
  • 5) Must have at least one measurable lesion as defined by the RECIST standard;
  • 6) Expected survival time ≥ 6 months;

  • 7) Heart function:

    1. Cardiac ultrasound detection LVEF ≥ 50%;
    2. EKG indicates no myocardial ischemia;
    3. no history of arrhythmia requiring drug intervention before enrollment;

  • 8) Patients must fully recover from the acute toxic effects of all previous anti-cancer chemotherapy:

    1. Myelosuppressive chemotherapy: at least 21 days after the last myelosuppressive chemotherapy (42 days if nitrosourea was used earlier);
    2. Experimental drugs or anti-cancer therapies other than chemotherapy: Do not use within the first 28 days of the planned start of doxycycline. Full recovery from the clinically significant toxicity of the therapy must be clearly identified;
    3. Hematopoietic growth factor: at least 14 days after the last dose of long-acting growth factor or 3 days after the last dose of short-acting growth factor;
    4. immunotherapy: at least 42 days after completing any type of immunotherapy (except steroids), such as immune checkpoint inhibitors and tumor vaccines;
    5. X-ray therapy (XRT): at least 14 days after local palliative XRT ( small range of mouth); if other solid bone marrow (BM) irradiation, including prior radioactive iodized meta-iodobenzidine (131I-MIBG) treatment, You must end at least 42 days;
    6. Stem cell infusion without total body irradiation (TBI): There is no evidence of active graft-versus-host disease, and transplantation or stem cell infusion must end at least 56 days;

  • 9) For patients who are not known to have BM:

    1. Absolute neutrophil count (ANC) ≥ 1.0 × 109 / L;
    2. Platelet count ≥100.0 × 109 / L;
    3. hemoglobin ≥90 g / L;

  • 10) Liver and kidney function should meet the following standards:

    1. Bilirubin (combined + unbound total) ≤ 2.5 × upper limit of normal value (ULN) (corresponding to age), patients with Gilbert's syndrome can be enrolled according to the researchers' judgment
    2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
    3. Estimated glomerular filtration rate ≥ 30 mL / min / 1.73 m2 or serum creatinine (Cr) ≤ 1.5ULN;
  • 11) During the participation in the study, be able to comply with outpatient treatment, laboratory monitoring and necessary clinical visits;
  • 12) The parent/ guardian of the child or adolescent subject has the ability to understand, agree, and sign the research informed consent (ICF) and applicable child consent form before initiating any protocol-related procedures; subject to parent/ guardian consent Candidates have the ability to express consent (if applicable).

Exclusion Criteria:

  • 1) Previous or concurrent active clinical cardiovascular disease including congenital heart disease or pericardial disease, history of heart failure, myocardial infarction, coronary heart disease, heart valve disease, cardiomyopathy, arrhythmia (including persistent atrial fibrillation, Complete left bundle branch block, frequent ventricular early); or the QT interval (QTc) after the current corrected heart rate is extended> 480 milliseconds;
  • 2) previous severe skin diseases;
  • 3) previous allergic asthma or severe allergic disease;
  • 4) Poorly controlled hypertension and diabetes;
  • 5) Have a history of other tumors, except for cured cervical cancer or skin basal cell carcinoma;
  • 6) Patients with hepatitis B surface antigen-positive;
  • 7) Patients infected with HIV or syphilis;
  • 8) Patients who have received organ transplants in the past;
  • 9) Uncontrolled active systemic bacterial, viral or fungal infections;
  • 10) Contraindications to high-dose hormone use, such as uncontrollable high blood sugar, gastric ulcer or mental illness;
  • 11) Patients who have used a total cumulative dose of doxorubicin ≥ 450 mg / m2, or a total cumulative dose of epirubicin ≥ 550 mg / m2, or previously used anthracyclines to cause heart disease;
  • 12) Have a serious neurological or psychiatric history, including epilepsy or autism.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PLD+CTX+VCR
CTX 1g/m2/d，D1-2 VCR 1.5mg/m2，D1
Drug: pegylated liposomal doxorubicin, cyclophosphamide, vincristine,
PLD 40mg/m2 ; PLD 50mg/m2 ; PLD 60mg/m2 ; Maximum tolerated dose； Dose-limiting toxicity
Other Names:
  • Doxorubicin Hydrochloride Liposome Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose
Time Frame: At the end of Cycle 1 (each cycle is 21 days)
Maximum tolerated dose
At the end of Cycle 1 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse event
Time Frame: through study completion, an average of 1 year
Hematological and non-hematological toxicity (NCI CTCAE v5.0)
through study completion, an average of 1 year
Objective Response Rate
Time Frame: At the end of Cycle 2 (each cycle is 21 days)
Complete remission + partial remission
At the end of Cycle 2 (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

December 30, 2019

Primary Completion (ANTICIPATED)

August 30, 2020

Study Completion (ANTICIPATED)

November 30, 2020

Study Registration Dates

First Submitted

December 24, 2019

First Submitted That Met QC Criteria

December 25, 2019

First Posted (ACTUAL)

December 30, 2019

Study Record Updates

Last Update Posted (ACTUAL)

December 30, 2019

Last Update Submitted That Met QC Criteria

December 25, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CV-1-19

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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