DCV in the Treatment of Recurrence and Refractory Childhood Solid Tumors

NCT04213612 | Unknown Phase 1

• 1 other identifier: CV-1-19
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Unrecognized Condition

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  Maximum tolerated dose

  At the end of Cycle 1 (each cycle is 21 days)

Secondary Outcomes (2)

• Adverse event

  through study completion, an average of 1 year

• Objective Response Rate

  At the end of Cycle 2 (each cycle is 21 days)

Study Arms (1)

PLD+CTX+VCR

EXPERIMENTAL

CTX 1g/m2/d，D1-2 VCR 1.5mg/m2，D1

Drug: pegylated liposomal doxorubicin, cyclophosphamide, vincristine,

Interventions

pegylated liposomal doxorubicin, cyclophosphamide, vincristine, DRUG

PLD 40mg/m2 ; PLD 50mg/m2 ; PLD 60mg/m2 ; Maximum tolerated dose； Dose-limiting toxicity

Also known as: Doxorubicin Hydrochloride Liposome Injection

PLD+CTX+VCR

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \) Age: 1-18 years;
• \) ECOG PS score: 0-1 points;
• \) Patients with solid tumors confirmed by histopathology in children;
• \) Patients who have progressed, relapsed, or are refractory after first-line treatment (there is no complete or partial response after recent treatment);
• \) Must have at least one measurable lesion as defined by the RECIST standard;
• \) Expected survival time ≥ 6 months;
• \) Heart function:
• Cardiac ultrasound detection LVEF ≥ 50%;
• EKG indicates no myocardial ischemia;
• no history of arrhythmia requiring drug intervention before enrollment;
• \) Patients must fully recover from the acute toxic effects of all previous anti-cancer chemotherapy:
• Myelosuppressive chemotherapy: at least 21 days after the last myelosuppressive chemotherapy (42 days if nitrosourea was used earlier);
• 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;
• 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;
• immunotherapy: at least 42 days after completing any type of immunotherapy (except steroids), such as immune checkpoint inhibitors and tumor vaccines;

You may not qualify if:

• \) 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;
• \) previous severe skin diseases;
• \) previous allergic asthma or severe allergic disease;
• \) Poorly controlled hypertension and diabetes;
• \) Have a history of other tumors, except for cured cervical cancer or skin basal cell carcinoma;
• \) Patients with hepatitis B surface antigen-positive;
• \) Patients infected with HIV or syphilis;
• \) Patients who have received organ transplants in the past;
• \) Uncontrolled active systemic bacterial, viral or fungal infections;
• \) Contraindications to high-dose hormone use, such as uncontrollable high blood sugar, gastric ulcer or mental illness;
• \) 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;
• \) Have a serious neurological or psychiatric history, including epilepsy or autism.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Related Publications (12)

• Singal PK, Deally CM, Weinberg LE. Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol. 1987 Aug;19(8):817-28. doi: 10.1016/s0022-2828(87)80392-9. No abstract available.

  PMID: 3320376 BACKGROUND

• Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979 Nov;91(5):710-7. doi: 10.7326/0003-4819-91-5-710.

  PMID: 496103 BACKGROUND

• Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003 Jun 1;97(11):2869-79. doi: 10.1002/cncr.11407.

  PMID: 12767102 BACKGROUND

• Abu Lila AS, Ishida T, Kiwada H. Recent advances in tumor vasculature targeting using liposomal drug delivery systems. Expert Opin Drug Deliv. 2009 Dec;6(12):1297-309. doi: 10.1517/17425240903289928.

  PMID: 19780711 BACKGROUND

• Gabizon AA. Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. Cancer Res. 1992 Feb 15;52(4):891-6.

  PMID: 1737351 BACKGROUND

• Northfelt DW, Martin FJ, Working P, Volberding PA, Russell J, Newman M, Amantea MA, Kaplan LD. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma. J Clin Pharmacol. 1996 Jan;36(1):55-63. doi: 10.1002/j.1552-4604.1996.tb04152.x.

  PMID: 8932544 BACKGROUND

• O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. doi: 10.1093/annonc/mdh097.

  PMID: 14998846 BACKGROUND

• Schmitt CJ, Dietrich S, Ho AD, Witzens-Harig M. Replacement of conventional doxorubicin by pegylated liposomal doxorubicin is a safe and effective alternative in the treatment of non-Hodgkin's lymphoma patients with cardiac risk factors. Ann Hematol. 2012 Mar;91(3):391-7. doi: 10.1007/s00277-011-1308-y. Epub 2011 Aug 18.

  PMID: 21850390 BACKGROUND

• Judson I, Radford JA, Harris M, Blay JY, van Hoesel Q, le Cesne A, van Oosterom AT, Clemons MJ, Kamby C, Hermans C, Whittaker J, Donato di Paola E, Verweij J, Nielsen S. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001 May;37(7):870-7. doi: 10.1016/s0959-8049(01)00050-8.

  PMID: 11313175 BACKGROUND

• Beverdam A, Meijlink F. Expression patterns of group-I aristaless-related genes during craniofacial and limb development. Mech Dev. 2001 Sep;107(1-2):163-7. doi: 10.1016/s0925-4773(01)00450-6.

  PMID: 11520673 BACKGROUND

• Wagner HE, Gilg M, Baer HU. [Characteristics of tumor diseases in patients with colorectal cancer]. Helv Chir Acta. 1993 Mar;59(4):701-3. German.

  PMID: 8473195 BACKGROUND

• Lu S, Wang J, Huang J, Sun F, Zhu J, Que Y, Li H, Guo Y, Cai R, Zhen Z, Sun X, Zhang Y. Pegylated liposomal doxorubicin combined with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory solid tumor: a single-arm, open-label, phase I study. EClinicalMedicine. 2024 Jun 20;73:102701. doi: 10.1016/j.eclinm.2024.102701. eCollection 2024 Jul.

  PMID: 39007065 DERIVED

Related Links

• Singal, P.K., C.M. Deally and L.E. Weinberg, Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol, 1987. 19(8): p. 817-28.
• Von Hoff, D.D., et al., Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med, 1979. 91(5): p. 710-7
• Swain, S.M., F.S. Whaley and M.S. Ewer, Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer, 2003. 97(11): p. 2869-79
• Abu A L, Ishida T, Kiwada H. Recent advances in tumor vasculature targeting using liposomal drug delivery systems.\[J\]. Expert Opinion on Drug Delivery, 2009, 6(12):1297.
• Gabizon AA. Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes\[J\]. Cancer Research, 1992, 52(4):891-896.
• Northfelt D W, Martin F J, Working P, et al. Doxorubicin Encapsulated in Liposomes Containing Surface-Bound Polyethylene Glycol: Pharmacokinetics, Tumor Localization, and Safety in Patients
• Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer.
• Schmitt, C.J., et al., Replacement of conventional doxorubicin by pegylated liposomal doxorubicin is a safe and effective alternative in the treatment of non-Hodgkin's lymphoma patients with cardiac risk factors. Ann Hematol, 2012. 91(3): p. 391-7
• Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group
• Marina, N.M., et al., Dose escalation and pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in children with solid tumors: a pediatric oncology group study. Clin Cancer Res, 2002. 8(2): p. 413-8.
• Munoz, A., et al., Pegylated liposomal doxorubicin hydrochloride (PLD) for advanced sarcomas in children: preliminary results. Pediatr Blood Cancer, 2004. 43(2): p. 152-5.

MeSH Terms

Interventions

liposomal doxorubicin; Cyclophosphamide; Vincristine

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Yizhuo Zhang

  Sun Yat-sen University CancerCenter

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yizhuo Zhang

CONTACT

02087342459; zhangyzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: December 24, 2019
• First Posted: December 30, 2019
• Study Start: December 30, 2019
• Primary Completion: August 30, 2020
• Study Completion: November 30, 2020
• Last Updated: December 30, 2019

Record last verified: 2019-12