Nanoparticle Albumin-Bound Rapamycin, Temozolomide, and Irinotecan Hydrochloride in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

NCT02975882 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: ADVL1514NCI-2016-01412UM1CA097452
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 21

Brief Summary

This phase I trial studies the side effects and best dose of nanoparticle albumin-bound rapamycin when given together with temozolomide and irinotecan hydrochloride in treating pediatric patients with solid tumors that have come back after treatment and a period of time during which the tumor could not be detected or has not responded to treatment. Nanoparticle albumin-bound rapamycin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nanoparticle albumin-bound rapamycin, temozolomide, and irinotecan hydrochloride may cause the cancer to stop growing or shrink for a period of time and may lessen the symptoms that are caused by the cancer.

Conditions

Childhood Solid Neoplasm; Recurrent Malignant Solid Neoplasm; Recurrent Primary Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Primary Central Nervous System Neoplasm

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Cycle 1 and 2 Dose Limiting Toxicities Attributable to Nanoparticle Albumin-bound Rapamycin

  Number of patients with cycle 1 and 2 dose limiting toxicities possibly, probably, or definitely attributable with nanoparticle albumin-bound rapamycin stratified by dose level.

  Up to 42 days

• Number of Patients With Adverse Events

  The number of patients with adverse events that are at least possibly attributable to nanoparticle albumin-bound rapamycin stratified by dose level.

  Up to 24 months

• Area Under the Serum of Nanoparticle Albumin-bound Rapamycin Concentration Curve

  Median with minimum and maximum values of the area under the drug concentration over time curve stratified by dose level.

  Days 1, 2, 3, 4, and 8

Secondary Outcomes (1)

• Number of Patients With Antitumor Activity of Nanoparticle Albumin-bound Rapamycin

  Up to 24 months

Study Arms (1)

Treatment (nab-rapamycin, temozolomide, irinotecan)

EXPERIMENTAL

Patients receive nanoparticle albumin-bound rapamycin IV over 30 minutes on days 1 and 8 beginning on cycle 1. Patients also receive temozolomide PO and irinotecan hydrochloride PO on days 1-5 beginning on cycle 2. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sirolimus Albumin-bound Nanoparticles; Drug: Temozolomide

Interventions

Irinotecan Hydrochloride DRUG

Given PO

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, CPT11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U 101440E, U-101440E, U101440E

Treatment (nab-rapamycin, temozolomide, irinotecan)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nab-rapamycin, temozolomide, irinotecan)

Pharmacological Study OTHER

Correlative studies

Treatment (nab-rapamycin, temozolomide, irinotecan)

Sirolimus Albumin-bound Nanoparticles DRUG

Given IV

Also known as: ABI 009, ABI-009, ABI009, Albumin-bound Sirolimus, Fyarro, Nab-Rapamycin, Nab-sirolimus, Nanoparticle Albumin-Bound Rapamycin, Nanoparticle Albumin-bound Sirolimus, Sirolimus Albumin-bound Particles, Sirolimus Protein-bound Particles

Treatment (nab-rapamycin, temozolomide, irinotecan)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ

Treatment (nab-rapamycin, temozolomide, irinotecan)

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have a body surface area (BSA) of \>= 0.2 m\^2 at the time of study enrollment
• Patients with recurrent or refractory solid tumors, including CNS tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
• Patients must have either measurable or evaluable disease
• Patient's current disease state must be one for which there is no known curative therapy
• Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation \[TBI\]):

You may not qualify if:

• 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; 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 an effective contraceptive method both during and for 6 months after participation in this study; abstinence is an acceptable method of contraception
• Patients receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
• 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
• Patients must not have received enzyme-inducing anticonvulsants for at least 7 days prior to enrollment
• Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, and others) are not eligible
• Patients must not be receiving any strong CYP3A4 or P-glycoprotein (P-gp) inducers or inhibitors within 7 days prior to enrollment; moderate inducers or inhibitors of CYP3A4 and P-gp should also be avoided during ABI-009 treatment, if possible
• Patients with interstitial lung disease and/or pneumonitis are not eligible
• Patients with a history of allergic reactions attributed to compounds of similar composition, including macrolide and ketolide antibiotics, temsirolimus/other mTOR inhibitors, temozolomide or irinotecan are not eligible
• Patients with hypersensitivity to albumin are not eligible
• Patients who have had or are planning to have the following invasive procedures are not eligible:
• Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment
• Subcutaneous port placement or central line placement is not considered major surgery; external central lines must be placed at least 3 days prior to enrollment and subcutaneous ports must be placed at least 7 days prior to enrollment
• Core biopsy within 7 days prior to enrollment

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (21)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Cramer SL, Reddy AT, Minard CG, Voss S, Fox E, Liu X, Denic K, Reid JM, Weigel BJ. A Phase 1 Study of ABI-009 (Nab-sirolimus) in Combination With Temozolomide and Irinotecan in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors-A Children's Oncology Group Pediatric Early Phase Clinical Trial Network Study ADVL1514. Cancer Med. 2024 Nov;13(21):e70376. doi: 10.1002/cam4.70376.

  PMID: 39487711 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

Irinotecan; Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

16264470064

Study Officials

• Stuart L Cramer

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 29, 2016
• Study Start: August 15, 2017
• Primary Completion: March 31, 2022
• Study Completion: December 31, 2024
• Last Updated: January 14, 2025
• Results First Posted: March 30, 2023

Record last verified: 2025-01

Locations

US (21)