Everolimus for Cancer With TSC1 or TSC2 Mutation

NCT02201212 | Completed Phase 2 Results DMC

• 2 other identifiers: 14-229CRAD001MUS217T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

In this research study, the investigators are evaluating the clinical benefit of everolimus in cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations. This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug called everolimus to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved everolimus for your type of cancer. Everolimus is a drug that may stop cancer cells from growing by blocking an important factor (mTOR) involved in the growth of cells. This drug has been used in treatment for other cancers and is approved by the Food and Drug Administration for treatment of several types of cancer, including renal cell carcinoma. Treatment with this drug has been associated with responses in some patients whose cancers had mutations in TSC1 or TSC2. The investigators think that patients whose tumors have mutations in TSC1 or TSC2 may have a good chance of responding to treatment with drugs like everolimus.

Conditions

TSC1; TSC2; Tuberous Sclerosis Complex; MTOR

Keywords

TSC1; TSC2; Tuberous Sclerosis Complex; MTOR

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  RECIST 1.1 criteria for Objective Response: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Baseline, Every 8 weeks, 2 Years

Secondary Outcomes (4)

• Duration of Response

  Baseline, Every 8 weeks, 2 Years

• Progression-free Survival

  Baseline, Up to 2 Years

• Overall Survival

  4 Years

• Toxicity Rate

  2 Years

Study Arms (1)

Everolimus

EXPERIMENTAL

Everolimus * Fixed doses orally once a day per each 28 day cycle * Participants will stay on study as long as they do not progress for a maximum of 24 months. * Tumor assessments will be performed after every 2 cycles for as long as they are on study.

Drug: Everolimus

Interventions

Everolimus DRUG

Also known as: Afinitor®, Zortress, Afinitor Disperz®, RAD001

Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed advanced malignancy that is either metastatic and/or unresectable and/or recurrent, with confirmed inactivating mutations in TSC1 or TSC2, or activating mutations in MTOR, identified in any CLIA-certified laboratory. All genetic findings must be reviewed by the study PI, Dr. David Kwiatkowski, prior to study entry.
• Biopsy of a primary or metastatic lesion must have been performed within the past two years. Sufficient pathologic material must be available to enable whole exome sequencing at the time of study entry.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
• Participants may have received any number of prior therapies, from 0 to \> 10, but prior treatment with PI3-kinase or mTOR inhibitors is not permitted.
• Age ≥ 18 years.
• ECOG performance status \<2 (see Appendix A).
• Participants must have normal organ and marrow function as defined below:
• Leukocytes ≥3,000/mcL
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥9.0 gr/dL
• Total bilirubin ≤1.5 ULN
• AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal. Patients with confirmed liver metastases are permitted to have AST/ALT at levels ≤ 5X the institutional upper limit of normal.
• Creatinine ≤ 1.5 X the institutional upper limit of normal.
• Total cholesterol \< 300 mg/dL

You may not qualify if:

• Participants who have had any of the following:
• chemotherapy in the previous 2 weeks (6 weeks for nitrosoureas or mitomycin C)
• radiotherapy within 3 weeks
• investigational agents within 3 weeks prior to entering the study
• patients who have not recovered from significant (in the opinion of the investigator) adverse events due to previous agents administered.
• Child-Pugh B or C hepatic impairment. Patients with a history of hepatitis or significant exposure risk should be tested for hepatitis B and C with serologic markers: HBsAg, HBs Ab, HBcoreIgG Ab, HCV Ab. Patients with active hepatitis B or C are excluded.
• Any prior exposure to any PI3 kinase or mTOR inhibitor agent.
• Participants may not be receiving any other research study agents.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Asymptomatic or treated brain metastases are acceptable.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus.
• A list of prohibited medications on study are listed in Section 5.5
• Chronic treatment with corticosteroids or other immunosuppressive therapy.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because everolimus has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with everolimus, breastfeeding should be discontinued if the mother is treated with everolimus. These potential risks may also apply to other agents used in this study.
• Individuals with a recent history of a different malignancy are ineligible except for the following circumstances: 1) Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years OR are deemed by the investigator to be at low risk for recurrence of that malignancy; 2) Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Tuberous Sclerosis

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. David Kwiatkowski
• Organization: Dana Farber Cancer Institute

dk@rics.bwh.harvard.edu

8573070781

Study Officials

• David Kwiatkowski, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 23, 2014
• First Posted: July 28, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: September 16, 2020
• Results First Posted: September 16, 2020

Record last verified: 2020-09

Locations

US (2)