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GlioblastomaPhase 1/2GEINOGLASNCT03466450

Glasdegib (PF-04449913) With Temozolomide Newly Diagnosed Glioblastoma

A Phase 1/2 study testing PF-04449913 and Temozolomide Oral Capsule in people with Glioblastoma, run by Grupo Español de Investigación en Neurooncología at 8 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Glioblastomas (GBMs) are the most common malignant primary brain tumors. Despite multimodality aggressive therapies (surgery followed by chemoradiotherapy based on TMZ and adjuvant TMZ), median overall survival is only 12 to 15 months. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Glioblastoma
What is being tested?
PF-04449913 and Temozolomide Oral Capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
8 sitesSpain
Study dates
15 Mar 2018to 29 Nov 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and the willingness to sign a written informed consent document.
  • Male or Female ≥18 years old.
  • Newly diagnosed GBM confirmed by biopsy or resection no more than 4 to 6 weeks before registration.
  • Patients candidates for Stupp treatment
  • Patients must have at least 15 unstained slides or 1 tissue block (frozen or paraffin embedded) available from a prior biopsy or surgery (archival tumor material).
  • Patients must have sufficient time for recovery from prior surgery (at least 4 weeks).
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  • ECOG ≤ 1.
  • Adequate hematologic function: Hematocrit ≥ 29%, Leukocytes > 3,000/mcL, ANC ≥ 1,500 cells/ul, platelets ≥ 100,000 cells/ul.
  • Adequate liver function: Bilirubin ≤ 2 x ULN; AST (SGOT) ≤ 2.5 X ULN
  • Creatinine within normal institutional limits or creatinine clearance > 60 mL/min for subjects with creatinine levels above institutional normal.
  • The effects of SHH pathway inhibitors on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence; surgical sterilization) prior to study entry and for the duration of study participation and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
  • Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 2 weeks prior to starting treatment.
  • Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.

Who cannot join

  • Presence of extracranial metastatic disease.
  • Participants may not be receiving any other investigational agents.
  • Patients must not have received prior Gliadel wafers.
  • Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
  • Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol.
  • Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication in tablet form.
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  • Congenital or known history of long QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular tachyarrhythmia, right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF New York Association class III or IV).
  • Current (or within 6 months) significant cardiovascular disease, including, but not limited to myocardial infarction, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism, bradycardia defined as <50 bpms.
  • Active cardiac dysrhythmias of NCI CTCAE Grade ≥2 (eg, atrial fibrillation) or QTcF interval (QTc using Fridericia's formula) >470 msec.
  • Active and clinically significant infections.
  • Current use or anticipated requirement for drugs known to be moderate or strong cytochrome p450 inhibitors.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
  • Patients will not be eligible if they have evidence of other malignancy requiring therapy other than surgery within the last 3 years.
  • Patients who have had prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy (as gliosis/scarring from these modalities may limit delivery).
  • Patients will not be eligible if they present with leptomeningeal dissemination.
  • Pregnant women are excluded from this study because the potential for teratogenic or abortifacient effects is unknown (glasdegib has been shown to be teratogenic in nonclinical embryo-fetal development studies in rats and mice at subtherapeutic exposures). Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated.
  • HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to glasdegib.
  • Other severe acute or chronic medical condition, uncontrolled intercurrent illness or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of the study treatment.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Spain8 sites

  • Institut Catalá de Oncología Badalona/Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital del Mar

    Barcelona, 08003

  • Hospital Clínic i Provincial de Barcelona

    Barcelona, 08036

  • Institut Catalá de Oncología Girona/Hospital Universitari Dr. Josep Trueta

    Girona, 17007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Ramón y Cajal

    Madrid

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Universitario y Politécnico La Fe

    Valencia, 46009

Other trials in Spain

About this study

Official title: Phase Ib/II Multicentric Study Combining Glasdegib (PF-04449913) With Temozolomide in Patients With Newly Diagnosed Glioblastoma, Safety and Preliminary Efficacy for the Combination

Glioblastomas (GBMs) are the most common malignant primary brain tumors. Despite multimodality aggressive therapies (surgery followed by chemoradiotherapy based on TMZ and adjuvant TMZ), median overall survival is only 12 to 15 months. This dramatic behavior is mainly due to the high invasiveness and proliferation rate of GBM.

In addition, GBM exhibits a high resistance to standard chemotherapy and radiotherapy. Current strategies for the treatment of GBM are only palliative, and include surgical resection (which is frequently incomplete due to the proximity of the tumour to vital brain structures) and focal radiotherapy. A large number of chemotherapeutic agents (e.g. alkylating agents such as TMZ and nitrosoureas such as carmustine) have also been tested, but they display limited efficacy.

Read more

The current gold standard first line treatment for glioma for patients less than 70 years old includes radiation and concurrent TMZ followed by adjuvant TMZ (i.e., the "Stupp regimen"). However, results are disappointing and there is an unmet medical need of new drugs in this setting.

Glasdegib (SHH pathway inhibitor) is a rational therapeutic agent for patients with newly diagnosed Glioblastoma since inhibits SHH pathway interfering with cancer stem cells and endothelial migration.

Conditions
Glioblastoma
Being tested
PF-04449913, Temozolomide Oral Capsule
Keywords
glioblastoma, glasdegib, temozolomide, combined therapy
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-04449913Drug

    Also called Glasdegib

    Glasdegib (3 dose levels will be evaluated: 100mg QD, 150mg QD and 200mg QD, or 75-50mg) will be administered:

    During concurrent phase concomitantly with radiation and Extended to the resting period (glasdegib will not be stopped in the 4 weeks of radiotherapy resting period).

    During adjuvant therapy with Temozolomide Oral Capsule. Additional treatment with glasdegib beyond 6 sequential TMZ cycles will continue until progression, unacceptable toxicity, non-compliance, consent withdrawal and/or 2 years of glasdegib administration.

  • Temozolomide Oral CapsuleDrug

    During RT, patients will receive Temozolamide (TMZ). All patients will be given TMZ at 75 mg/m2

    /d concurrently with RT for a maximum of 42 days. At 4 weeks after RT completion, patients will start taking TMZ at 150 mg/m2/d for the first 5 days of a 28-day cycle. If first cycle is well tolerated, patients will receive TMZ at 200 mg/m2/d for the first 5 days of every subsequent 28-day cycle for another 5 cycles.

Study groups in NCT03466450
Study groupRoleWhat they receive
Glasdegib and Temozolomide Oral CapsuleExperimentalDuring Phase Ib, Four to six weeks after surgical diagnosis, concurrent with radiotherapy (STUPP) + temozolomide (75mg/m2/day for 42 days) + PF-04449913 (Glasdegib) (3 dose levels will be evaluated: 100mg QD, 150mg QD and 200mg QD, or 75-50mg) will be administered. During Phase II, Radiation therapy, temozolomide and glasdegib will be administered. This last, as the dose that have been selected previously, based on the Phase Ib results. Glasdegib ( PF-04449913) recommended dose until progresion of disease, unacceptable toxicity, non-compliance, consent withdrawal up to 2 years.
Receives: Drug: PF-04449913; Drug: Temozolomide Oral Capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Glasdegib Dose

    For Phase Ib, The recommended dose for phase 2 (RDP2) of Glasdegib administered with temozolomide during and after RT.

    Measured: 12 weeks

  2. Overall survival

    For Phase II, time between the start of treatment to death

    Measured: 15 months

Secondary outcomes (3)

  1. Progression Free Survival

    Time between the start of treatment and progression of disease

    Measured: 24 months

  2. Adverse events (safety)

    Based on the number and type of adverse events reported since the start of treatment and throughout the study period.

    Measured: 24 months

  3. Response to treatment

    Based on RANO criteria

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2018
  2. Study start15 Mar 2018
  3. Primary completion29 Nov 2023
  4. Study completion29 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Phase Ib/II, multicentric, non-randomized, open label
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03466450
Sponsor's protocol ID
GEINO-1602
Other IDs
2017-002410-31, 2017
Acronym
GEINOGLAS
Status last verified
Mar 2024
First submitted
27 Feb 2018
Last updated
28 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Vaz-Salgado MA, Del Barco S, Sepulveda JM, Alonso M, Pineda E, Balana C, Martinez-Garcia M, Girones R. Glasdegib in combination with temozolomide and radiotherapy in adult patients with newly diagnosed glioblastoma: the phase Ib/II GEINO 1602 trial. Nat Commun. 2025 Dec 4;17(1):86. doi: 10.1038/s41467-025-66747-z.

    PubMed 41345097

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PF-04449913 and Temozolomide Oral Capsule in people with Glioblastoma, run by Grupo Español de Investigación en Neurooncología at 8 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Glasdegib Dose (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03466450, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2024.

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