Tipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma - Study Results

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Brain and Central Nervous System Tumors
Interventions:	Drug: Tipifarnib Radiation: Local Irradiation

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants from PBTC member institutions were enrolled on the phase I component between 01/30/2004 and 01/19/2006. The phase II component of the study opened on 06/02/2006 and completed accrual on 12/26/2007.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Tipifarnib 100-mg/m2	Tipifarnib 100 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only.
Tipifarnib 125-mg/m2	Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II.
Tipifarnib 150-mg/m2	Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only.

Description

Tipifarnib 100-mg/m2

Tipifarnib 100 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses.

Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy.

All participants treated at this dose level were enrolled to the phase I part of the study only.

Tipifarnib 125-mg/m2

Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses.

Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy.

The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II.

Tipifarnib 150-mg/m2

Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses.

Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy.

All participants treated at this dose level were enrolled to the phase I part of the study only.

Participant Flow: Overall Study

	Tipifarnib 100-mg/m2	Tipifarnib 125-mg/m2	Tipifarnib 150-mg/m2
STARTED	5	40	6
Enrolled in Phase I	5	6	6
Maximum Tolerated Dose (MTD) Estimation	3 ^[1]	6	5 ^[2]
Enrolled in Phase II	0 ^[3]	40 ^[4]	0 ^[5]
COMPLETED	0	1	0
NOT COMPLETED	5	39	6
Adverse Event	1	7	2
Death	1	0	0
Non-compliance	0	0	1
Withdrawal by Subject	0	4	1
Disease progression	3	28	2

[1]	2 participants enrolled in the phase I part did not complete the 8 week MTD estimation period.
[2]	One participant enrolled in the phase I part did not complete the 8 week MTD estimation period.
[3]	Participants treated at the 100 mg/m2 dose level did not participate in the phase II part.
[4]	This number includes the 6 patients enrolled on the phase I part.
[5]	Participants treated at the 150 mg/m2 dose level did not participate in the phase II part.

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Tipifarnib 100-mg/m2	Tipifarnib 100 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only.
Tipifarnib 125-mg/m2	Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II.
Tipifarnib 150-mg/m2	Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only.

Description

Tipifarnib 100-mg/m2

Tipifarnib 100 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses.

Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy.

All participants treated at this dose level were enrolled to the phase I part of the study only.

Tipifarnib 125-mg/m2

Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses.

Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy.

The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II.

Tipifarnib 150-mg/m2

Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period – first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses.

Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy.

All participants treated at this dose level were enrolled to the phase I part of the study only.

Baseline Measures

	Tipifarnib 100-mg/m2	Tipifarnib 125-mg/m2	Tipifarnib 150-mg/m2	Total
Number of Participants [units: participants]	5	40	6	51
Age [units: participants]
<=18 years	5	40	6	51
Between 18 and 65 years	0	0	0	0
>=65 years	0	0	0	0
Age [units: years] Median ( Full Range )	5.87 ( 4.68 to 8.23 )	5.48 ( 3.33 to 16.47 )	5.84 ( 4.55 to 13.75 )	5.72 ( 3.33 to 16.7 )
Gender [units: participants]
Female	1	25	5	31
Male	4	15	1	20
Region of Enrollment [units: participants]
United States	5	40	6	51

Outcome Measures

Show All Outcome Measures

1. Primary:

Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy [ Time Frame: Day 1 of tipifarnib therapy to week 8 ]

Show Outcome Measure 1

2. Primary:

Progression-free Survival (PFS) [ Time Frame: Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks. ]

Show Outcome Measure 2

3. Secondary:

Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation [ Time Frame: Baseline and two weeks post completion of radiation ]

Show Outcome Measure 3

4. Secondary:

Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation. [ Time Frame: Baseline and two weeks post completion of radiation ]

Show Outcome Measure 4

5. Secondary:

Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation [ Time Frame: Baseline and two weeks post completion of radiation ]

Show Outcome Measure 5

6. Secondary:

Mean Tumor to Gray Matter Ratio Measured at Baseline [ Time Frame: Baseline ]

Show Outcome Measure 6

7. Secondary:

Mean Tumor to White Matter Ratio Measured at Baseline [ Time Frame: Baseline ]

Show Outcome Measure 7

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Pediatric Brain Tumor Consortium (James M. Boyett, Ph.D)
Organization: Pediatric Brain Tumor Consortium
phone: 901-595-4986
e-mail: james.boyett@stjude.org

Publications of Results:

Haas-Kogan DA, Banerjee A, Kocak M, Prados MD, Geyer JR, Fouladi M, McKnight T, Poussaint TY, Broniscer A, Blaney SM, Boyett JM, Kun LE. Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem glioma. Neuro Oncol. 2008 Jun;10(3):341-7. Epub 2008 Apr 16.

Responsible Party:	James M. Boyett, PhD, Executive Director of the Operations and Biostatistics Center for the Pediatric Brain Tumor Consortium, Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:	NCT00079339 History of Changes
Other Study ID Numbers:	CDR0000355177, PBTC-014
Study First Received:	March 8, 2004
Results First Received:	April 30, 2010
Last Updated:	November 5, 2010
Health Authority:	United States: Food and Drug Administration