Everolimus With and Without Temozolomide in Adult Low Grade Glioma
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ClinicalTrials.gov Identifier: NCT02023905 |
Recruitment Status
:
Recruiting
First Posted
: December 30, 2013
Last Update Posted
: January 17, 2018
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Condition or disease | Intervention/treatment | Phase |
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Low Grade Glioma WHO Grade II Astrocytomas Oligodendrogliomas Mixed Oligoastrocytomas | Drug: Everolimus Drug: Temozolomide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 159 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | PI3K/mTOR Pathway Activation Selected Phase II Study of Everolimus (RAD001) With and Without Temozolomide in the Treatment of Adult Patients With Supratentorial Low-Grade Glioma |
Study Start Date : | February 2014 |
Estimated Primary Completion Date : | January 2019 |
Estimated Study Completion Date : | January 2019 |

Arm | Intervention/treatment |
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Experimental: Arm 1
If the tumor is 1p/19q intact, then patients will be further selected by whether or not their tumor demonstrates activation of the PI3K/mTOR pathway. If activation is present, patients will be treated in Arm 1 with single-agent everolimus at 10 mg daily continuously. In all arms, treatment with everolimus will continue for up to 24 cycles, after which patients will be followed with interval MRIs until progression.
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Drug: Everolimus
Other Name: RAD001, Afinitor
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Experimental: Arm 2
If the tumor is 1p/19q intact, then patients will be further selected by whether or not their tumor demonstrates activation of the PI3K/mTOR pathway. If activation is not present, patients will be treated in Arm 2 with combined everolimus and Temozolomide. Everolimus will be given at 10 mg daily continuously, and Temozolomide will be dosed initially at 150 mg/m2/day for 5 days out of a 28-day cycle. In all arms, treatment with everolimus will continue for up to 24 cycles, after which patients will be followed with interval MRIs until progression. In Arm 2, TMZ will be stopped after 12 cycles.
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Drug: Everolimus
Other Name: RAD001, Afinitor
Drug: Temozolomide
Other Name: Temodar, TMZ
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Experimental: Arm 3
If the tumor is 1p/19q intact, then patients will be further selected by whether or not their tumor demonstrates activation of the PI3K/mTOR pathway. If 1p/19q co-deletion is present, patients will be treated in Arm 3 with single-agent everolimus at 10 mg daily continuously. In all arms, treatment with everolimus will continue for up to 24 cycles, after which patients will be followed with interval MRIs until progression.
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Drug: Everolimus
Other Name: RAD001, Afinitor
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- Arm 1 & 2 Progression-free survival [ Time Frame: 33 Months ]
- Arm 3 progression-free survival [ Time Frame: 38 Months ]
- Median and distribution of overall survival (OS) and PFS [ Time Frame: 36 Months ]
- Objective Response Rate (ORR) [ Time Frame: 36 Months ]
- Number of adverse events related to combination treatment [ Time Frame: 36 Months ]
- Rate of Reduction in Seizures [ Time Frame: 36 Months ]

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥ 18 years
- KPS ≥ 60
- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 10^9/L, Platelets ≥ 100 x 10^9/L, Hb ≥ 9.0 g/dL;
- Adequate liver function as shown by: Total serum bilirubin ≤ 2.0 mg/dL, ALT and AST ≤ 2.5x ULN, INR ≤ 2;
- Adequate renal function: serum creatinine ≤1.5 x ULN;
- Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication with confirmed reduction of lab values to within eligibility parameters;
- Signed informed consent prior to any screening procedures
- Histologically proven supratentorial low-grade glioma at initial diagnosis; pathology must have been reviewed by UCSF neuropathology. Eligible low-grade gliomas include: astrocytoma, oligodendroglioma and mixed oligoastrocytoma. Pilocytic astrocytomas are excluded.
- Patient's tumor must have documentation of the presence of an IDH-1 and/or IDH-2 mutation of any type.
- Results of 1p/19q chromosomal status and pPRAS40 testing must be available to permit treatment selection.
- Evaluable disease
- Must begin treatment within 120 days of surgical procedure
Exclusion Criteria:
- No prior tumor treatment except for surgery at diagnosis, and must have adequately recovered from surgery
- Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) or to temozolomide
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus or temozolomide
- Uncontrolled diabetes mellitus as defined by HbA1c > 8.0% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary;
- Any severe and/or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; symptomatic congestive heart failure of New York heart Association Class III or IV; active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA); known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air); active, bleeding diathesis;
- Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed, and treatment with low dose Decadron (≤ 3mg daily) is allowed;
- Known history of HIV seropositivity;
- Positive serological test results for hepatitis B
- Positive serological test result for hepatitis C
- Recipients of live attenuated vaccines within 1 week of start of treatment and during the study. Avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines;
- History of another primary malignancy, with the exceptions of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uterus, or breast, unless the patient has been disease free for ≥ 3 years;
- History of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study;
- Currently part of or have participated in any clinical investigation with an investigational therapeutic drug within 1 month prior to dosing;
- Pregnant or nursing (lactating) women;
- Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, who are not willing to use adequate methods of contraception during the study and for 8 weeks after the end of treatment.
- Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
- Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02023905
Contact: Jennifer Clarke, MD, MPH | 415-353-2966 | Jennifer.Clarke@ucsf.edu | |
Contact: Tiffany Jones, MPH | 415-353-9641 | Tiffany.Jones@ucsf.edu |
United States, California | |
University of California, San Francisco | Recruiting |
San Francisco, California, United States, 94143-0372 | |
Contact: Jennifer Clarke, MD, MPH 415-353-2966 Jennifer.Clarke@ucsf.edu | |
Contact: Tiffany Jones 415-353-9641 Tiffany.Jones@ucsf.edu | |
Principal Investigator: Jennifer Clarke, MD |
Principal Investigator: | Jennifer Clarke, MD, MPH | University of California, San Francisco |
Additional Information:
Responsible Party: | University of California, San Francisco |
ClinicalTrials.gov Identifier: | NCT02023905 History of Changes |
Other Study ID Numbers: |
Novartis- CRAD001CUS225T Cancer Center # 131012 ( Other Identifier: UCSF ) |
First Posted: | December 30, 2013 Key Record Dates |
Last Update Posted: | January 17, 2018 |
Last Verified: | January 2018 |
Additional relevant MeSH terms:
Glioma Astrocytoma Oligodendroglioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Temozolomide Everolimus Sirolimus |
Dacarbazine Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |