NCT04796012

Brief Summary

This trial is a multi-center, non-randomized, open-label Phase I/II study evaluating the feasibility and efficacy of vincristine, irinotecan, temozolomide, and atezolizumab in children with relapsed/refractory solid tumors.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at P25-P50 for phase_1

Timeline
7mo left

Started Apr 2023

Typical duration for phase_1

Geographic Reach
1 country

7 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress85%
Apr 2023Jan 2027

First Submitted

Initial submission to the registry

February 22, 2021

Completed
18 days until next milestone

First Posted

Study publicly available on registry

March 12, 2021

Completed
2.1 years until next milestone

Study Start

First participant enrolled

April 18, 2023

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2027

Last Updated

June 2, 2026

Status Verified

May 1, 2026

Enrollment Period

3.7 years

First QC Date

February 22, 2021

Last Update Submit

May 29, 2026

Conditions

Keywords

Relapsed solid tumorRefractory solid tumorRhabdomyosarcoma

Outcome Measures

Primary Outcomes (6)

  • Number of participants with Dose-limiting Toxicities (DLTs)

    DLT is defined as any event that is possibly, probably, or definitely attributable to the treatment regimen and exceeds the protocol defined threshold for severity

    Beginning of cycle 3, or 30 days after the second cycle has started, whichever is earlier (each cycle is 21 days)

  • Number of participants with Acute Adverse Events (AEs)

    AE is defined as any untoward or unfavorable medical occurrence in a human research study participant, including any abnormal sign, symptom, clinical event, or disease, temporally associated with the subject's participation in the research, whether or not it is considered related to the subject's participation in the research. AEs will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Adverse events not specifically defined in the NCI CTCAE will be scored on the Adverse Event log according to the general guidelines provided by the NCI CTCAE. Acute AEs are events occurring in the time period from the signing of the informed consent, through 42 days post treatment.

    42 days post treatment.

  • Number of participants with Serious Adverse Events (SAEs)

    SAEs are those events, occurring at any dose, which meets any of the following criteria: 1) results in death, 2) is life-threatening, 3) results in inpatient hospitalization or prolongation of existing hospitalization, 4) results in a persistent or significant disability/incapacity, 5) results in a congenital anomly/birth defect in a neonate/infant born to a mother exposed to the IMP; or 6) based upon appropriate medical judgement, may jeopardize the subject's health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. SAE determination does not require the event to be related to the research. SAEs will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Serious adverse events not specifically defined in the NCI CTCAE will be scored on the Adverse Event log according to the general guidelines provided by the NCI CTCAE.

    48 months

  • Objective response rate (ORR)

    ORR is the percentage of participants whose confirmed best overall response was either a partial response (PR) or a complete response (CR) based upon independent review and per RECIST v1.1, modified INRC, or RANO criteria as appropriate.

    Up to 18 weeks post treatment

  • Objective response rate (ORR)

    ORR is the percentage of participants whose confirmed best overall response was either a partial response (PR) or a complete response (CR) based upon independent review and per RECIST v1.1, modified INRC, or RANO criteria as appropriate.

    Week 18 up to 24 months post treatment

  • Objective response rate (ORR)

    ORR is the percentage of participants whose confirmed best overall response was either a partial response (PR) or a complete response (CR) based upon independent review and per RECIST v1.1, modified INRC, or RANO criteria as appropriate.

    Month 24 up to end of study (approximately 48 months)

Secondary Outcomes (9)

  • Duration of response

    Up to 18 weeks post treatment

  • Duration of response

    Week 18 up to 24 months post treatment

  • Duration of response

    Month 24 up to end of study (approximately 48 months)

  • Progression-free survival (PFS)

    Up to 18 weeks post treatment

  • Progression-free survival (PFS)

    Week 18 up to 24 months post treatment

  • +4 more secondary outcomes

Study Arms (2)

Feasibility Cohort: Patients with relapsed or refractory solid tumors

EXPERIMENTAL

Six (6) participants with relapsed or refractory solid tumor will be enrolled. Atezolizumab will be administered in combination with vincristine, irinotecan, and temozolomide for up to 2 years or until the participant experiences disease progression or an unacceptable toxicity.

Drug: AtezolizumabDrug: VincristineDrug: IrinotecanDrug: Temozolomide

Rhabdomyosarcoma (RMS) Cohort: Patients with rhabdomyosarcoma

EXPERIMENTAL

Seventeen (17) participants with RMS, including the six participants from the Feasibility Cohort, will be enrolled. At least 8 of the RMS participants must have a tumor that expresses the protein PD-L1. Atezolizumab will be administered in combination with vincristine, irinotecan, and temozolomide for up to 2 years or until the participant experiences disease progression or an unacceptable toxicity.

Drug: AtezolizumabDrug: VincristineDrug: IrinotecanDrug: Temozolomide

Interventions

Feasibility and RMS Cohorts: Administered at 100 mg/m\^2 (max 200 mg) IV or PO 1 hour before irinotecan injection on Days 1-5 if each 21-day cycle

Also known as: Temozolomide Capsules, Temodar
Feasibility Cohort: Patients with relapsed or refractory solid tumorsRhabdomyosarcoma (RMS) Cohort: Patients with rhabdomyosarcoma

Feasibility and RMS Cohorts: Administered at 15 mg/kg (max 1,200 mg) IV on Day 1 of each 21-day cycle

Also known as: Tecentriq
Feasibility Cohort: Patients with relapsed or refractory solid tumorsRhabdomyosarcoma (RMS) Cohort: Patients with rhabdomyosarcoma

Feasibility and RMS Cohorts: Administered at 1.5 mg/m\^2 (max 2 mg) IV on Day 1 of each 21-day cycle

Also known as: Vincristine Sulfate Injection, Oncovin, Vincasar PES, Vincrex
Feasibility Cohort: Patients with relapsed or refractory solid tumorsRhabdomyosarcoma (RMS) Cohort: Patients with rhabdomyosarcoma

Feasibility and RMS Cohorts: Administered at 50 mg/m2 IV on Days 1-5 of each 21-day cycle

Also known as: Irinotecan Hydrochloride Injection, Campto
Feasibility Cohort: Patients with relapsed or refractory solid tumorsRhabdomyosarcoma (RMS) Cohort: Patients with rhabdomyosarcoma

Eligibility Criteria

Age6 Months - 30 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Signed informed consent
  • Relapsed or refractory solid tumor after at least one prior course of therapy.
  • Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
  • Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met.
  • No metastatic or primary disease affecting the brainstem, midbrain, pons, or cerebellum, or within 10 mm of optic nerve
  • No history of leptomeningeal disease
  • No history of intracranial or spinal cord hemorrhage
  • No evidence of progression of neurologic deficit, in the investigator's judgment, within 7 days prior to initiation of study medications.
  • Must have histologically confirmed rhabdomyosarcoma (RMS) for RMS efficacy cohort.
  • Age ≥ 6 months and ≤ 30 years
  • Lansky Performance Status (patients \< 16 years old) or Karnofsky Performance Status (patients ≥ 16 years old) ≥ 50
  • Ability to comply with the study protocol, in the investigator's judgment
  • For RMS efficacy cohort, disease must be measurable as defined by RECIST v1.1.
  • For the feasibility cohort, disease must be evaluable, but patients enrolled in the feasibility cohort will be prospectively assessed for measurable disease, RMS patients will also be included in the RMS efficacy cohort.
  • Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
  • +35 more criteria

You may not qualify if:

  • Pregnancy or breast-feeding:
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
  • Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
  • Medical conditions that are excluded:
  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Guillain-Barré syndrome, multiple sclerosis, or Kawasaki syndrome with the following exceptions:
  • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met at study initiation: (1) Rash must cover less 10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium \&amp;gt; 1.5 mmol/L, calcium \&amp;gt; 12 mg/dL or corrected serum calcium \&amp;gt; ULN)
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Patients with indwelling catheters (e.g., PleurX®) are allowed.
  • Uncontrolled tumor-related pain
  • Patients requiring pain medication must be on a stable regimen at study entry for at least 2 weeks. Intermittent use of as-needed medication is allowed during this period.
  • Clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (at the discretion of the treating physician)
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • +39 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

The University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Rhabdomyosarcoma

Interventions

atezolizumabVincristineIrinotecanTemozolomide

Condition Hierarchy (Ancestors)

MyosarcomaNeoplasms, Muscle TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsSarcoma

Intervention Hierarchy (Ancestors)

Vinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesCamptothecinDacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-Ring

Study Officials

  • Arhanti Sadanand, MD

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Pediatrics

Study Record Dates

First Submitted

February 22, 2021

First Posted

March 12, 2021

Study Start

April 18, 2023

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2027

Last Updated

June 2, 2026

Record last verified: 2026-05

Locations