Niraparib vs Temozolomide for Brain Cancer
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Ivy Brain Tumor Center
Must not be taking: PARP inhibitors
Disqualifiers: Metastatic disease, Pneumonitis, Cirrhosis, others
Stay on Your Current Meds
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma multiforme (GBM). The main questions it aims to answer are:
Does niraparib improve progression-free survival (PFS) compared to TMZ?
Does niraparib improve overall survival (OS) compared to TMZ?
Participants will be randomly assigned to one of two treatment arms: niraparib or TMZ.
* study drug (Niraparib) or
* comparator drug (Temozolomide - which is the standard approved treatment for MGMT unmethylated glioblastoma).
The study medication will be taken daily while receiving standard of care radiation therapy (RT) for 6-7 weeks.
Participants may continue to take the niraparib or TMZ adjuvantly as long as the cancer does not get worse or completion of 6 cycles of treatment (TMZ). A total of 450 participants will be enrolled in the study.
Participants' tasks will include:
* Complete study visits as scheduled
* Complete a diary to record study medication
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should have stable or decreased doses of dexamethasone, not exceeding 5 mg daily, within 7 days before randomization.
What data supports the effectiveness of the drug Niraparib for brain cancer?
Niraparib has been shown to be effective in treating brain metastases in patients with ovarian and endometrial cancer, as it can enter the brain and suppress tumor growth. In one case, a patient with brain metastases from endometrial cancer remained free of disease progression for 6 months after treatment with Niraparib.
12345Is there safety data available for Temozolomide in humans?
Temozolomide has been studied in humans, particularly for brain cancer, and is generally considered safe when used in combination with other treatments like radiotherapy. It has been shown to reduce the odds of death in patients with glioblastoma, a type of brain cancer, indicating its safety and effectiveness in this context.
678910How does the drug Niraparib differ from Temozolomide for brain cancer?
Niraparib is a PARP inhibitor, which works by preventing cancer cells from repairing their DNA, while Temozolomide is a chemotherapy drug that can cross the blood-brain barrier to treat brain tumors. Niraparib's unique mechanism of action may offer a novel approach compared to the traditional chemotherapy method of Temozolomide.
811121314Eligibility Criteria
This trial is for adults over 18 with a new diagnosis of glioblastoma multiforme (GBM) that hasn't been treated yet, except for surgery. Participants need to be in good physical condition and not planning pregnancy or breastfeeding. They must agree to use effective contraception.Inclusion Criteria
My diagnosis is a new brain tumor identified as GBM.
I am 18 years old or older.
I am considered suitable for a specific radiation therapy plan.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive daily study medication (Niraparib or Temozolomide) while undergoing standard of care radiation therapy for 6-7 weeks
6-7 weeks
Weekly visits during radiation therapy
Adjuvant Treatment
Participants may continue to take Niraparib or Temozolomide as long as the cancer does not progress or until completion of 6 cycles of treatment
Up to 6 cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Every 16 weeks on days of MRI
Participant Groups
The study compares the effectiveness of niraparib against temozolomide (TMZ), which is standard treatment for GBM without MGMT methylation. It will assess if niraparib can extend the time before cancer worsens or improve overall survival compared to TMZ.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A: NiraparibExperimental Treatment1 Intervention
Group II: Arm B: TemozolomideActive Control1 Intervention
Niraparib is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Zejula for:
- Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
- Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy
🇺🇸 Approved in United States as Zejula for:
- Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
- Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status
🇨🇦 Approved in Canada as Zejula for:
- Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ivy Brain Tumor CenterPhoenix, AZ
Moores UCSD Cancer CenterLa Jolla, CA
The NeuroMedical CenterBaton Rouge, LA
Thomas Jefferson UniversityPhiladelphia, PA
More Trial Locations
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Who Is Running the Clinical Trial?
Ivy Brain Tumor CenterLead Sponsor
GlaxoSmithKlineIndustry Sponsor
References
Successful treatment of a patient with brain metastases from endometrial cancer using Niraparib: a case report. [2021]Endometrial cancer (EC) is the second most common gynecologic malignancy in China, and the incidence and mortality rates have increased in recent years. Brain metastasis from EC is extremely rare, affecting only 0.3-1.16% of EC patients. The prognosis for patients with brain metastasis from EC is poor, with a median survival time of 3.5-6.5 months from the diagnosis of brain metastasis. Niraparib is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that uses the concept of synthetic lethality in the presence of a mutation in the breast cancer susceptibility gene (BRCA). Niraparib is recommended as a maintenance treatment for ovarian cancer patients with platinum-sensitive relapse and has been shown to increase progression-free survival. Niraparib was found to enter the brain via the blood-brain barrier, which resulted in a higher concentration of the drug in the brain tissues and better tumor-suppressing effects. There was none report about the applications of PARP inhibitor for endometrial cancer with brain metastases. Here, we present the case of a 62-year-old woman whose Peripheral blood gene detection had shown BRCA1 mutation with brain metastases from high-grade serous carcinoma of the endometrium who was successfully treated with Niraparib and remained free of disease progression for 6 months.
Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. [2019]Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The pivotal phase III clinical trial has shown improved progression-free survival in patients receiving niraparib compared with those receiving placebo.
Niraparib as maintenance therapy in a patient with ovarian cancer and brain metastases. [2021]Ovarian cancer is the second the most common gynaecological malignancy in developed countries. 70% of patients relapse in the first 3 years following debulking surgery and first-line chemotherapy. Niraparib is a poly adenosine diphosphate ribose polymerase inhibitor which uses the concept of synthetic lethality in the presence of a mutation in the breast cancer susceptibility gene (BRCA), and is now recommended as maintenance treatment in patients with platinum-sensitive relapse of ovarian cancer. It has been shown to increase progression-free survival. We present a case of a 68-year-old woman with brain metastases from high-grade serous ovarian cancer who has remained free of disease progression for longer than 17 months with niraparib use as maintenance treatment after second-line chemotherapy.
Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]Niraparib (Zejula™) is a PARP inhibitor which is approved for maintenance therapy in adults with advanced ovarian cancer in complete or partial response to platinum-based chemotherapy. In a placebo-controlled phase III trial in patients with newly diagnosed advanced ovarian cancer, niraparib significantly extended progression free survival in two predefined populations, namely a patient population with altered homologous-recombination DNA repair pathways [i.e. homologous-recombination deficiency positive (HRd)] and the overall trial population. A prespecified exploratory subgroup analysis indicated that niraparib was also efficacious in patients who were homologous recombination deficiency negative or homologous recombination proficient (HRp). Niraparib has a manageable tolerability profile with myelosuppression as the main safety concern. Haematological reactions were managed with monitoring and dose reduction or interruption. A weight- and platelet count-based individualised dosage regimen introduced during the trial (and subsequently approved) appeared to improve haematological tolerability. Niraparib is a useful option for first-line maintenance therapy for advanced ovarian cancer in adults who responded to platinum-based chemotherapy, regardless of homologous-recombination deficiency status and is a promising option for HRp patients, for whom maintenance treatment options are limited.
Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. [2021]To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.
Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. [2022]Patients with non-small-cell lung cancer (NSCLC) and brain metastases have previously been excluded from trials of bevacizumab because of suspected risk of CNS hemorrhage. This phase II trial, AVF3752g (PASSPORT), specifically addressed bevacizumab safety (incidence of grade > or = 2 CNS hemorrhage) in patients with NSCLC and previously treated brain metastases.
NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. [2023]A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.
Microdialysis measurement of intratumoral temozolomide concentration after cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, in a U87 glioma model. [2021]Combining anti-angiogenesis agents with cytotoxic agents for the treatment of malignant gliomas may affect the cytotoxic drug distribution by normalizing the blood-brain barrier (BBB). This study examines the intratumoral concentration of temozolomide (TMZ) in the presence and absence of the pan-VEGF receptor tyrosine kinase inhibitor, cediranib.
Odds of death after glioblastoma diagnosis in the United States by chemotherapeutic era. [2021]Bevacizumab (BZM) and temozolomide (TMZ) have been shown to be beneficial in the treatment of patients with glioblastoma. We sought evidence for the benefit of BZM in the general patient population at large. The Surveillance, Epidemiology, and End Results SEER database was queried for patients diagnosed with glioblastoma between 2000 and 2009, divided into a pre-TMZ era (January 2000-June 2003), a transitional era (July 2003-March 2005), a TMZ era (April 2005-October 2007), and a BZM-TMZ era (November 2007-December 2009). Binomial logit regression analyzed odds of death, taking into account age at diagnosis, tumor size, gender, race, marital status, radiotherapy, and extensive surgery. Compared with the pre-TMZ era, odds of death were decreased in the TMZ era by 12% (97.5% CI [confidence interval] 3-20%) 6 months after diagnosis and 36% (30-42%) a year after diagnosis; corresponding values for BZM-TMZ were 31% (24-37%) and 50% (45-55%). For era comparisons, decreases in odds of death were larger at 12 than 6 months; the opposite was true for extensive surgery and radiotherapy (P
Effects of Temozolomide and Radiotherapy on Brain Metastatic Tumor: A Systematic Review and Meta-Analysis. [2018]To systematically evaluate safety and efficacy of temozolomide plus radiotherapy in the treatment of brain metastasis.
Temozolomide for treating brain metastases. [2019]The metastasis of solid tumors to the brain is associated with a poor prognosis despite aggressive treatment. Available treatment options are limited, as many chemotherapeutic agents do not penetrate the blood-brain barrier. Temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) is a novel chemotherapeutic agent with a good safety profile that crosses the blood-brain barrier and has shown activity against many human solid tumors. In two phase II trials of temozolomide in heavily pretreated patients with various solid tumor brain metastases, temozolomide was safe and generally well tolerated and showed clinical activity, with three partial responses and 19 disease stabilizations. Results of a third randomized phase II trial of concurrent administration of temozolomide and radiation therapy followed by adjuvant temozolomide therapy compared with radiation alone showed a higher rate of complete and partial responses (objective response of 96% v 67%) and significantly more complete responses (38% v 33%, P =.017), primarily in patients with newly diagnosed brain and lung metastases.
A phase 2 study of radiosurgery and temozolomide for patients with 1 to 4 brain metastases. [2020]To determine if temozolomide reduces the risk of distant brain failure (DBF, metachronous brain metastases) in patients with 1 to 4 brain metastases treated with radiosurgery without whole-brain radiation therapy (WBRT).
Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner. [2021]Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models.
Cediranib enhances control of wild type EGFR and EGFRvIII-expressing gliomas through potentiating temozolomide, but not through radiosensitization: implications for the clinic. [2021]Glioblastomas (GBM) frequently overexpress the epidermal growth factor receptor (wtEGFR) or its mutant, EGFRvIII, contributing to chemo- and radioresistance. The current standard of care is surgery followed by radiation therapy with concurrent temozolomide (TMZ) followed by adjuvant TMZ. New treatment strategies for GBM include blockade of EGFR signaling and angiogenesis. Cediranib is a highly potent receptor tyrosine kinase inhibitor that inhibits all three VEGF receptors. This study investigated the radiosensitizing potential of cediranib in combination with TMZ in U87 GBM xenografts expressing wtEGFR or EGFRvIII. U87 GBM cells stably transfected with either wtEGFR or EGFRvIII were injected into the hind limbs of nude mice. Cediranib was dosed at 3 mg/kg daily five times a week orally for 2 weeks. TMZ was dosed at 10 mg/kg once only on day 0. Radiotherapy (RT) consisted of 3 fractions of 5 Gy (days 0-2). Cediranib did not radiosensitize either tumor type; however, cediranib did enhance the effectiveness of TMZ in both transfectants. Our results suggest that combining cediranib with temozolomide in the clinic will lead to improved tumor control.