A proof of concept clinical trial assessing the safety of the coordinated undermining of survival paths by 9 repurposed drugs combined with metronomic temozolomide (CUSP9v3 Treatment Protocol) for recurrent glioblastoma
- Conditions
- GlioblastomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004197-42-DE
- Lead Sponsor
- niversity Hospital of Ulm
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 10
1.Patients with a diagnosis of glioblastoma WHO grade IV (histologically confirmed by a pathologist). Patients with prior low-grade glioma are eligible if histological transformation to WHO grade IV glioblastoma was confirmed.
2.Progression (according to RANO criteria) after prior radiation and temozolomide treatment
3.No more than 3 prior episodes of tumor progression
4.= 4 weeks between surgical resection or chemotherapy
5.= 12 weeks since last radiotherapy
6.Patients > 18 years of age.
7.Karnofsky performance status (KPS) of = 70%
8.Stable steroid dose for = 1 week
9.QT interval < 410 ms on ECG
10.Haematocrit >29%
11.ANC >10³ cells/µl
12.Platelet count >105/µl
13.Maximum 5 years since last Pneumovax (or equivalent) and varicella vaccination
14.Serum creatinine, AST and bilirubin = 1.5 times the IULN
15.Female patients of childbearing potential with a negative pregnancy test within 7 days of initiation of study treatment. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
16.Male and female patients of reproductive potential who agree to employ an effective method of birth control throughout the study and for up to 6 months following discontinuation of study drug.*
17.Signed informed consent prior to initiation of any study procedure (Must understand, voluntarily sign the informed consent form and be able to adhere to the study visit schedule and other protocol requirements.)
* s. Appendix II – Pregnancy Prevention Risk Management Plan
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
1.Female patients who are pregnant or breast-feeding
2.Any uncontrolled/unstable medical condition except glioblastoma, including but not limited to uncontrolled/unstable hypertension, uncontrolled/unstable diabetes, uncontrolled endocrinopathies of any kind, uncontrolled/unstable psychiatric conditions
3.Renal failure (eGFR <60 ml/min)
4.Active infection
5.Therapeutic anticoagulation use
6.Prior stereotactic radiosurgery
7.Radiation implants
8.Radiolabeled monoclonal antibody therapy unless there was unequivocal disease progression (e.g. a new lesion or biopsy confirmed recurrence)
9.History of severe hypersensitivity reaction (=grade 3) to any component of the investigational drugs or excipients
10.Unable to undergo contrast-enhanced MRI
11.Patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drugs.
12.Current active second malignancy other than non-melanoma skin cancers and post-treatment of localized prostate cancer. Patients are not considered to have a currently active malignancy if they are in complete remission for > 3 years prior to study
13.Known HIV infection, active Hepatitis B or C infection
14.Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity (except alopecia) and delayed recovery following last temozolomide cycle
15.Additional anti-cancer treatment for glioblastoma other than study drug and supportive measures (i.e. dexamethasone)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to assess the safety and tolerability of the CUSP9v3 Treatment Protocol in patients with recurrent glioblastoma.;Secondary Objective: •Overall survival<br>•Progression-Free Survival<br>•Tumor Response<br>;Primary end point(s): The primary endpoint of this trial is the number of patients experiencing dose-limiting toxicity defined as:<br>-Either any unmanageable grade 3-4 toxicity at the end of the second treatment cycle<br>-Or inability to receive at least 7 of the 10 drugs, , all of them being given at =50% of the target doses<br>Modifications in terms of doses and/or number of drugs are accepted at any time during treatment.<br><br>;Timepoint(s) of evaluation of this end point: -Either any unmanageable grade 3-4 toxicity at the end of the second treatment cycle<br>-Or inability to receive at least 7 of the 10 drugs, will be decide at the weekly study visit within the inductioncycles
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Overall survival according to Kaplan-Meier estimates <br>•Progression-free survival according to Kaplan-Meier estimates <br>•Best tumor response according to the RANO criteria<br>;Timepoint(s) of evaluation of this end point: -Overall survival according to Kaplan-Meier estimates at every study visit (weekly; after three month every two weeks)<br>•Progression-free survival according to Kaplan-Meier estimates every month<br>Best tumor response according to the RANO criteria: after one year (end of Treatment) or at time of death