Study to evaluate the addition of an experimental drug, CC-90010, to the usual treatment of brain cancer after surgery

Trial details

Who runs it

Celgene Corp.

Trial code

EU 2024-511171-15-00

Record updated

2024. július 4.

Original description

• To determine the safety and tolerability of CC-90010 in combination with TMZ as adjuvant therapy. • To determine the safety and tolerability of CC-90010 in combination with TMZ+RT as concomitant therapy. • To determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of CC-90010 in combination with TMZ as adjuvant therapy. • To determine the MTD and/or the RP2D of CC-90010 in combination with TMZ+RT as concomitant therapy.Read full original descriptionShow less

A Phase 1b, open-label, dose-finding study of CC-90010 in combination with temozolomide with or without radiation therapy in subjects with newly diagnosed glioblastoma

• To determine the safety and tolerability of CC-90010 in combination with TMZ as adjuvant therapy. • To determine the safety and tolerability of CC-90010 in combination with TMZ+RT as concomitant therapy. • To determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of CC-90010 in combination with TMZ as adjuvant therapy. • To determine the MTD and/or the RP2D of CC-90010 in combination with TMZ+RT as concomitant therapy.

Inclusion: Males and females of ≥ 18 years of age; Subjects must have life expectancy of at least 6 months; Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1; Subject must have the laboratory values at screening as per protocol; Females of childbearing potential (FCBP) must: • Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, one highly effective contraceptive method plus one barrier method. These measures should be used from signing the ICF, throughout the study (including dose interruptions), and for at least 46 days following the last dose of CC 90010 and at least 180 days after the last dose of TMZ. The longest contraception period that is required must be followed. • Have two negative pregnancy tests as verified by the Investigator prior to starting CC-90010. •Avoid conceiving for at least 46 days after the last dose of CC-90010 and for at least 180 days after the last dose of TMZ. The longest contraception period that is required must be followed. • Agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact; Males must practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or a FCBP and will avoid conceiving from signing the ICF, while participating in the study, during dose interruptions, and for at least 106 days following CC- 90010 discontinuation and at least 180 days after the last dose of TMZ, even if he has undergone a successful vasectomy. The longest contraception period that is required must be followed; Males must agree to refrain from donating semen while on study drug and for 106 days after discontinuation of CC-90010 or 180 days after the last dose of TMZ, whichever is longer; Females must agree to refrain from donating ova while on study treatment and for 46 days after the last dose of CC-90010 or 180 days after the last dose of TMZ, whichever is longer; Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted; Subject is willing and able to adhere to the study visit schedule and other protocol requirements; Subject has newly diagnosed, histologically confirmed WHO Grade IV Glioblastoma and must have undergone complete or partial tumor resection; Subject must have recovered from the effects of surgery, including post-operative infections or complications; For Concomitant Therapy: Prior tumor resection up to 8 weeks prior to the first dose of CC 90010; For Adjuvant Therapy: Subject must have recently completed standard or a hypofractionated course of radiotherapy with TMZ chemotherapy, and then have an MRI documenting stable disease prior to the first dose of CC 90010; For Adjuvant Therapy: a. All AEs resulting from prior RT+TMZ chemotherapy must have resolved to NCI CTCAE (v5.0) Grade 1 (except for laboratory parameters outlined below). b. Subject must have not experienced significant toxicity to prior RT+TMZ (i.e., Grade 4 hematological toxicity). c. Subject must have received at least 80% of the planned standard doses of RT and/or TMZ administered throughout the 42 day concomitant period (up to 49 days); Subject with archival tumor tissue suitable for molecular genetic testing must give permission to access and test the tissue.

Exclusion: Prior chemotherapy or other anti-tumor treatment for GBM (either approved or investigational) except for surgery and for the Adjuvant Therapy cohort, mandatory concomitant TMZ+RT; Subject with a requirement for ongoing treatment with therapeutic dosing of anti-coagulants, or for ongoing prophylactic anticoagulation. Low dose low molecular weight heparin for catheter maintenance is allowed; History of concurrent second cancers requiring active and ongoing systemic treatment, except non-melanoma skin cancer, completely resected cervical carcinoma in situ, low risk prostate cancer, either totally resected or irradiated with curative intent (with PSA of less than or equal to 0.1 ng/mL) or under active surveillance. Other cancers for which the subject has completed potentially curative treatment more than 3 years prior to study entry are allowed; Evidence of history of bleeding diathesis. Any hemorrhage/bleeding event > CTCAE Grade 2 or haemoptysis > 1 teaspoon within 4 weeks prior to the first dose of CC-90010; Subject with known prior episodes of non-arteritic anterior ischemic optic neuropathy (NAION) should be excluded from the study. CC-90010 should be used with caution in subjects with retinitis pigmentosa; Subject who requires increasing doses of corticosteroids to treat symptomatic cerebral edema within 14 days prior to the first dose of CC- 90010; Known chronic active hepatitis B or C virus (HBV, HCV) infection. • Subjects who are seropositive due to HBV vaccination are eligible. • Subjects who have no active viral infection and are under adequate prophylactics against HBV re-activation are eligible; Subject has any condition that confounds the ability to interpret data from the study; Subject with poor bone marrow reserve as assessed by Investigator such as in conditions requiring regular hematopoietic support; Subject has persistent diarrhea due to a malabsorptive syndrome NCI CTCAE Grade ≥ 2, despite medical management, or any other significant GI disorder that could affect the absorption of CC-90010; Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages; Evidence of recent, symptomatic CNS hemorrhage on baseline MRI or CT scan; Impaired cardiac function or clinically significant cardiac diseases, as those listed in the protocol; Known HIV infection; Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating (or compromise compliance) in the study or would place the subject at unacceptable risk if he/she were to participate in the study; Known symptomatic acute or chronic pancreatitis; Pregnant or nursing females.

EU CTIS 2024-511171-15-00