Neoplasms

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Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Taxane

Dose Escalation followed by Dose Expansion.

Dose Escalation Phase: The maximum tolerated dose (MTD) for TPI 287 given concurrently with Fractionated Stereotactic Radiotherapy (FSRT) will be determined using the standard 3+3 study design.

Dose Expansion Phase: Participants will be treated with TPI 287 at MTD given concurrently with FSRT to further assess toxicity and tumor response.

TPI 287 is an infusion given through veins. Dose escalation will begin at 14 mg/m\^2/dose. Dose expansion will begin at the maximum tolerated dose (MTD).

TPI 287

The prescription dose will be 25 gray (Gy) in 5 daily fractions delivered to the planning target volume (PTV).

Fractionated Stereotactic Radiotherapy (FSRT)

Solmaz Sahebjam, M.D.

The main purpose of this study is to see whether addition of TPI 287 to FSRT is safe and tolerable. Researchers also want to find out if adding TPI 287 to FSRT can help with better controlling the growth of brain lesions in people with brain metastases from their cancer.

Standard of care for treatment of patients with brain metastases, which are considered not surgically removable, is radiation therapy to the brain lesions. This treatment is called Fractionated Stereotactic Radiotherapy (FSRT) and is given without chemotherapy and usually over 5 days.

Researchers of this study want to find out if adding an investigational drug, called TPI 287, to standard radiation therapy (FSRT) can help people with brain metastases from cancer. TPI 287 is a drug that is being tested and is not approved for sale in the United States by the U.S. Food and Drug Administration (FDA).

Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases

A Phase 1 Study of TPI 287 Concurrent With Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases From Advanced Breast and Non-Small Cell Lung (NSCL) Cancer

MTD of TPI 287 given concurrently with Fractionated Stereotactic Radiotherapy (FSRT) to treat brain metastases from advanced solid tumors.

The percentage of participants with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents. Complete Response (CR): The tumor is no longer seen on two sequential MRI scans, and the patient is on no steroids or only adrenal-maintenance dose of steroids. Partial Response (PR): ≥ 50% decrease in the product of two diameters of target lesions on two sequential MRIs, taking as reference the baseline product of two diameters, provided that the patient has not had his/her dose of steroids increased since the last evaluation period. Stable Disease (SD): The scan shows no change, taking as reference the smallest product of diameters while on study. Patient should be receiving stable or decreasing doses of steroids.

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) definition of Progression follows. One or more of the following must occur: 20% or greater increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration.

Cortice Biosciences, Inc.

H. Lee Moffitt Cancer Center and Research Institute

Rare Diseases

Recurrence

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Carbon Ion Radiotherapy in the RD determined within the Phase I Part of the Trial

Standard Precision Radiotherapy performed as Fractionated Stereotactic Radiotherapy (FSRT) up to 36 Gy in single dosis of 2 Gy

Carbon Ion Radiotherapy in the RD determined within the Phase I part of the Study (10 x 3Gy E to 16 x 3 Gy E)

Carbon Ion Radiotherapy

Standard Treatment as Re-Irradiation performed as Fractionated Stereotactic Radiotherapy (FSRT)up to 36 Gy in single doses of 2 Gy

Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cautiously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV tumors.

Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the Glioblastoma (GBM) cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.

First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective.

In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy.

Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival.

Carbon Ion Radiotherapy for Recurrent Gliomas

Randomised Phase I/II Study to Evaluate Carbon Ion Radiotherapy Versus Fractionated Stereotactic Radiotherapy in Patients With Recurrent or Progressive Gliomas: The CINDERELLA Trial

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases	NCT02187822	Brain Metastase... Generalized Mal... Brain Lesions	TPI 287 Fractionated St...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Carbon Ion Radiotherapy for Recurrent Gliomas	NCT01166308	Glioma	Carbon Ion Radi... Fractionated St...	18 Years -	University Hospital Heidelberg
Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases	NCT02187822	Brain Metastase... Generalized Mal... Brain Lesions	TPI 287 Fractionated St...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for fractionated stereotactic radiotherapy (fsrt)