Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases

• ClinicalTrials.gov Identifier: NCT02187822
• Recruitment Status: Terminated
• First Posted: July 11, 2014
• Last Update Posted: February 4, 2021
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Cortice Biosciences, Inc.
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Tracking Information

• First Submitted Date: July 9, 2014
• First Posted Date: July 11, 2014
• Last Update Posted Date: February 4, 2021
• Actual Study Start Date: October 9, 2014
• Actual Primary Completion Date: February 20, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2014)

Maximum Tolerated Dose (MTD) of TPI 287 [ Time Frame: Up to 2 years ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 2, 2014)

• Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]
  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.
• Progression Free Survival (PFS) Rate [ Time Frame: Up to 5 years ]
  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.

Original Secondary Outcome Measures (submitted: July 10, 2014)

Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]

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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases
• Official Title: 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
• Brief Summary: 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.

Detailed Description

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).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Brain Metastases
• Generalized Malignancy, Primary
• Brain Lesions

Intervention

• Drug: TPI 287
  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).
  Other Name: taxane
• Procedure: Fractionated Stereotactic Radiotherapy (FSRT)
  The prescription dose will be 25 gray (Gy) in 5 daily fractions delivered to the planning target volume (PTV).

Study Arms

Experimental: Dose Escalation + Dose Expansion

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.

Interventions:

• Drug: TPI 287
• Procedure: Fractionated Stereotactic Radiotherapy (FSRT)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 22, 2019): 15
• Original Estimated Enrollment (submitted: July 10, 2014): 34
• Actual Study Completion Date: March 31, 2018
• Actual Primary Completion Date: February 20, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Must have histologically or cytologically confirmed non-central nervous system primary solid malignancy.
• Must have pathologically or radiologically confirmed metastatic disease in the brain.
• Potential participants with up to 3 brain metastases (symptomatic and non-symptomatic) can be treated on this study. Maximum diameter of each brain lesion should be ≤ 5 cm. Maximum tumor volume ≤ 120 cc.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%).
• Life expectancy of greater than 12 weeks.
• Patients requiring treatment with corticosteroids are eligible.
• Treatment with non-enzyme inducing anti-seizure medications is allowed.
• Must have normal organ and marrow function.
• Systemic chemotherapy washout period ≥ 7 days. For investigational dugs and monoclonal antibodies washout period ≥ 5x drug half-life. There are no limitations on number of prior treatment regimens.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of TPI 287 administration.
• Prior brain surgery or radiation is allowed as long as the metastatic lesion(s) to be targeted in this study has not previously been treated with radiation.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have had chemotherapy within 1 week (6 weeks for nitrosoureas or mitomycin C) or investigational therapies/monoclonal antibodies within 5 half-life of investigational compound or those who have adverse events which are greater than grade 1 and are due to agents administered more than 1 week earlier. Bisphosphonates, endocrine therapy, and trastuzumab are permitted without restriction.
• Are receiving any other investigational agents.
• Previous treatment of the target lesions with radiation therapy.
• Have previously been treated with whole brain radiation.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TPI 287.
• Have brain metastases secondary to germ cell tumor or lymphoma malignancy.
• Women who are pregnant or nursing (lactating).
• Known contraindication to enhanced MRI and CT scan.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled seizure activity or psychiatric illness/social situations that would limit compliance with study requirements.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02187822
• Other Study ID Numbers: MCC-17816
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• Study Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Cortice Biosciences, Inc.

Investigators

• Principal Investigator: Solmaz Sahebjam, M.D.; H. Lee Moffitt Cancer Center and Research Institute

• PRS Account: H. Lee Moffitt Cancer Center and Research Institute
• Verification Date: February 2021