A phase I/II study of oral PHA-848125AC given daily for 14 consecutive days every 3 weeks in recurrent malignant glioma

Phase 1

• Conditions: Phase I Part: Recurrent Malignant GliomaPhase II Part: Recurrent Glioblastoma Multiforme; MedDRA version: 9.1Level: LLTClassification code 10065443Term: Malignant glioma; MedDRA version: 9.1Level: LLTClassification code 10018337Term: Glioblastoma multiforme

• Registration Number: EUCTR2006-003193-10-FR
• Lead Sponsor: erviano Medical Sciences S.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-05-22
• Study Completion: 2012-08-31
• Last Update Posted: 13 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Phase I part:
1.Signed and dated IRB/IEC-approved Informed Consent
2.Histologically proven supratentorial brain tumor (e.g. anaplastic astrocytoma [WHO grade III], recurrent or progressive low-grade glioma, oligodendroglioma, ependymoma), at recurrence after prior standard therapy. Inclusion of other histologies possible after approval by the Investigator and the Sponsor
3.Recurrence or progression after prior standard treatment with surgery, if feasible, radiotherapy and chemotherapy. Patient may have received more than 1 line of prior chemotherapy
4.Age = 18 years
5.KPS = 70
6.Estimated life expectancy of at least 3 months
7.Negative pregnancy test (if female in reproductive years)
8.Agreement upon the use of effective contraceptive methods (hormonal or barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation, if men and women of child producing potential
9.Adequate liver function:
- Bilirubin = 1.5 upper limit of normal (ULN)
- Albumin = 3.0 g/dL
- AST (SGOT), ALT (SGPT) =2.5 ULN
- Alkaline phosphatase = 2.5 ULN
10.Adequate renal function:
- Serum creatinine =1.5 mg/dL (or =133 µmol/L)
11.Adequate hematologic status:
- ANC =1,500 cells/mm3
- Platelet count = 100,000 cells/mm3
- Hemoglobin =10.0 g/dL
12.At the time of start of treatment, at least 4 weeks must have elapsed since completion of surgery, radiotherapy and chemotherapy (at least 6 weeks since completion of prior nitrosurea therapy)
13.With the exception of alopecia, resolution of all acute toxic effects of any prior surgery, radiotherapy, radiosurgery or chemotherapy to NCI CTC (Version 3.0) grade = 1 and to the baseline laboratory values as defined in Inclusion Criteria Number 9, 10, 11
14.Concurrent corticosteroids allowed, with dose stable for at least 7 days before treatment
15.Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol
16.Capability to swallow capsules intact (without chewing, crushing, or opening)
17.If on treatment with antiepileptic drugs (AEDs), AEDs should be non enzyme-inducing (non-EIAEDs). (Not Applicable to patients enrolled in the EIAEDs subset at the RP2D)
18.Patients on treatment with enzyme-inducing antiepileptic drugs (EIAEDs). (Applicable only to patients enrolled in the EIAEDs subset at the RP2D)
19.Patients should continue on the same anticonvulsant(s) for 2 weeks prior to treatment; patients with tumor-related tremors and/or seizures can be enrolled if well controlled by specific therapy.

Phase II part:

1.Signed and dated IRB/IEC-approved Informed Consent
2.Histologically proven (at diagnosis) glioblastoma (GBM)
3.Patients in first relapse, following 1st line chemotherapy (maximum 1 line of prior chemotherapy, either administered at initial diagnosis or at a recurrence)
4.Presence of at least one =1.5 cm2 bi-dimensionally measurable lesion by gadolinium (Gd)-enhanced MRI scan, indicating progressive or recurrent disease, obtained at least 12 weeks after standard external-beam radiotherapy and within 14 days prior to treatment
5.Age = 18 years
6.KPS = 70
7.Estimated life expectancy of at least 3 months
8.Negative pregnancy test (if female in reproductive years)
9.Agreement upon the use of effective contraceptive methods (hormonal or barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation, if men and women of child-producing potential
10.Adeq

Exclusion Criteria

Phase I and Phase II parts:
The presence of any of the following will exclude a subject from study enrollment:

1.Grade >1 retinopathy
2.Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis
3.Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment
4.Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
5.Pregnant or breast feeding women
6.Known infection with HIV, active hepatitis B or hepatitis C
7.Prior high-dose chemotherapy with bone marrow or stem cell support
8.Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
9.Patients with extra-brain metastases
10.Current enrollment in or participation in another therapeutic clinical trial within 4 weeks preceeding treatment start
11.Diabetes mellitus uncontrolled, or with clinical evidence of diabetic retinopathy, severe peripheral vascular disease or diabetic ulcers
12.Patients who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation or to the contrast medium
13.Gastrointestinal disease (e.g. Crohn’s disease, ulcerative colitis, or short gut syndrome) that would impact on drug absorption
14.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
15.Patients under treatment with anticoagulants or with coagulation disorders or with signs of hemorrhage at the baseline MRI
16.Patients treated with drugs which might inhibit CYP3A4
17.Patients treated with drugs which might induce CYP3A4 (except for patients taking EIAEDs and enrolled in the EIAEDs subset at the RP2D).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified