Actively Recruiting

Phase 1
Phase 2
Age: 12Years +
All Genders
ID07243470

A Multicenter, Open-label Phase I/II Trial to Assess Safety and Clinical Activity of Tarlatamab with Metronomic Temozolomide in Adolescents and Adults with High-Grade Brain Tumors

Led by Centre Leon Berard · Updated on 2026-05-27

70

Participants Needed

12

Research Sites

52 weeks

Total Duration

On this page

Sponsors

C

Centre Leon Berard

Lead Sponsor

A

Amgen

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating the safety and clinical activity of combining tarlatamab with a fixed dose of metronomic temozolomide in adolescents and adults who have high-grade central nervous system (CNS) tumors. The study involves two phases and includes three groups based on tumor histology: IDH-mutant glioma, other gliomas, and other CNS tumors. Patients must have tumors expressing DLL3, confirmed by immunohistochemistry (IHC) on archival tumor samples, which is done before starting the therapeutic part of the trial. Participants receive tarlatamab intravenously starting with a step dose in the first cycle, followed by regular doses every two weeks. Temozolomide is introduced from the second cycle at a continuous daily dose. The trial has two dose levels with different cycle lengths and dosing schedules. The study groups are non-randomized and open-label, with patients classified by tumor type. During the trial, participants will be assessed for dose-limiting toxicities during the first two cycles and clinical activity over 12 weeks. Researchers will monitor tumor response using iRANO criteria and track progression-free survival, overall survival, and adverse events for up to 12 months. Patients must undergo tumor tissue testing and provide informed consent. The study aims to understand the treatment's safety and effectiveness in controlling disease progression.

CONDITIONS

Brief Title

Combination of Tarlatamab and Temozolomide in Patients With Central Nervous System Tumors

Who Can Participate

Age: 12Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patients aged 12 years or older at time of informed consent.
  • Confirmed diagnosis of high-grade central nervous system malignant tumors: IDH-mutant glioma, other gliomas, or other CNS tumors.
  • Tumors must express DLL3 protein confirmed by immunohistochemistry on archival tumor samples.
  • Disease must be progressive or refractory after at least one standard therapy including radiotherapy.
  • Measurable or evaluable disease according to iRANO criteria.
  • Performance status: Karnofsky  70% for patients  16 years, Lansky  70% for patients 12-15 years, ECOG 0 or 1 for adults.
  • Life expectancy of at least 3 months.
  • Adequate blood, kidney, liver, heart, and lung function based on laboratory and clinical assessments.
  • Availability of a quality tumor tissue sample for testing.
  • Completed washout periods from prior anti-cancer treatments as specified.
  • For women of childbearing potential, negative pregnancy test and use of effective contraception.
  • Sexually active males must use adequate contraception.
  • Ability to understand and sign informed consent and comply with study procedures.
  • Coverage by medical insurance.
Not Eligible

You will not qualify if you...

  • Diagnosis of non-CNS tumors or diffuse intrinsic pontine glioma.
  • Current treatment with bevacizumab.
  • Prior treatment with DLL3-targeted therapies.
  • Neurologically unstable or requiring increasing corticosteroids within 7 days before treatment.
  • Significant CNS hemorrhage detected on baseline MRI.
  • Bulky tumors with severe mass effect or herniation.
  • Gastrointestinal conditions that affect oral drug absorption.
  • Recent abdominal fistula, perforation, or abscess.
  • Uncontrolled or significant heart disease.
  • Other malignancies expected to interfere with study evaluation unless stable for 2 years.
  • History of hypophysitis or pituitary dysfunction.
  • Severe allergies to study drugs or components.
  • Unresolved toxicities from prior therapy except specified exceptions.
  • History of arterial thrombosis or pulmonary embolism requiring anticoagulation.
  • Interstitial lung disease or active pneumonitis.
  • Recent live vaccine administration within 4 weeks.
  • Active or recent serious autoimmune disease requiring systemic treatment.
  • Active hepatitis B or C infection or HIV.
  • Prior organ or bone marrow transplant.
  • Any condition or therapy that may interfere with participation or study results.
  • Pregnant or breastfeeding women.

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Up to 12 months

Participants receive Tarlatamab and Temozolomide as part of the treatment for high-grade brain tumors. Tarlatamab is given initially as a step dose during the first cycle followed by regular doses every 2 weeks. Temozolomide is started continuously from the second treatment cycle.

Visits every 2 weeks during treatment cycles

Trial Site Locations

Total: 12 locations

1

Institut de Cancérologie de l'Ouest

Angers, France, 49055

Actively Recruiting

2

Hôpital Universitaire d'Angers

Angers, France, 49933

Not Yet Recruiting

3

CHU de Bordeaux

Bordeaux, France, 33000

Not Yet Recruiting

4

Hôpital Saint-André

Bordeaux, France, 33075

Not Yet Recruiting

5

Hôpital Neurologique Pierre Wertheimer

Bron, France, 69677

Actively Recruiting

6

Centre Oscar Lambret

Lille, France, 59000

Not Yet Recruiting

7

Centre Léon Bérard

Lyon, France, 69373

Actively Recruiting

8

Hôpital de la Timone - service adulte

Marseille, France, 13005

Actively Recruiting

9

Hôpital de la Timone - service pédiatrie

Marseille, France

Actively Recruiting

10

Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix

Paris, France, 75013

Not Yet Recruiting

11

IUCT - Claudius Regaud

Toulouse, France, 31100

Actively Recruiting

12

Institut Gustave Roussy

Villejuif, France, 94085

Not Yet Recruiting

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Research Team

P

Pierre LEBLOND, MD, PhD

A

Aurélien MAUREILLE, MD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

3

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Published Research Related To This Trial

Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours.

S Baruchel, M Diezi, D Hargrave...

https://pubmed.ncbi.nlm.nih.gov/16899365

Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group.

H Stacy Nicholson, Cynthia S Kretschmar, Mark Krailo...

https://pubmed.ncbi.nlm.nih.gov/17705175

Phase II, Open-Label, Randomized, Multicenter Trial (HERBY) of Bevacizumab in Pediatric Patients With Newly Diagnosed High-Grade Glioma.

Jacques Grill, Maura Massimino, Eric Bouffet...

https://pubmed.ncbi.nlm.nih.gov/29412784

Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children.

Alberto Broniscer, Murali Chintagumpala, Maryam Fouladi...

https://pubmed.ncbi.nlm.nih.gov/16200343

Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: a report of the Children's Oncology Group ACNS0423 study.

Regina I Jakacki, Kenneth J Cohen, Allen Buxton...

https://pubmed.ncbi.nlm.nih.gov/27006176