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Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme

Primary Purpose

Glioblastoma Multiforme

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

ABT-414

Temozolomide

Whole Brain Radiation

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring GBM

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Glioblastoma Multiforme (GBM)
70 or above on Karnofsky Performance Status
Adequate bone marrow function
Recurrent GBM per RANO criteria
Subjects must have confirmed EGFR amplification by central lab

Exclusion Criteria:

For Subjects with recurrent GBM in Arm B, subject has received prior treatment with bevacizumab, nitrosourea, or has secondary GBM
For Subjects with recurrent GBM in Arm C, subject has received prior treatment with bevacizumab, or has secondary GBM
Allergies to temozolomide, dacarbazine, IgG containing agents
Anti-cancer treatment 28 days prior to study Day 1, except in Arm B expanded cohort temozolomide therapy is allowed
Subjects that have had more than one disease recurrence

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm A

Arm B

Arm C

Arm Description

ABT-414 in combination with radiation and temozolomide

ABT-414 in combination with temozolomide

ABT-414 monotherapy

Outcomes

Primary Outcome Measures

Number and percentage of participants with adverse events

Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG)

Maximum concentration of ABT-414

Measurement of the maximum concentration of ABT- 414 in the blood

Number of Dose Limiting Toxicities

Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG)

Minimum Concentration of ABT-414

Measurement of the minimum concentration of ABT-414 in the blood

Half-life of ABT-414

Measurement of the clearance of ABT-414

Secondary Outcome Measures

Biomarker EGFR expression

Assessment of tumor biomarkers that may correlate with efficacy.

Progression Free Survival

Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not get worse.

Overall Survival

The overall response rate will be evaluated every 8 weeks at each assessment of disease according to RANO criteria, up to 28 months

Full Information

NCT ID

NCT01800695

First Posted

February 5, 2013

Last Updated

November 17, 2017

Sponsor

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT01800695

Brief Title

Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme

Official Title

A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Completed

Study Start Date

April 2, 2013 (Actual)

Primary Completion Date

June 19, 2017 (Actual)

Study Completion Date

June 19, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study is evaluating the safety and pharmacokinetics of ABT-414 in subjects with glioblastoma multiforme.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

GBM

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

202 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

ABT-414 in combination with radiation and temozolomide

Arm Title

Arm B

Arm Type

Experimental

Arm Description

ABT-414 in combination with temozolomide

Arm Title

Arm C

Arm Type

Experimental

Arm Description

ABT-414 monotherapy

Intervention Type

Drug

Intervention Name(s)

ABT-414

Other Intervention Name(s)

Depatuxizumab Mafodotin

Intervention Description

ABT-414 will be administered by intravenous infusion

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Intervention Description

Temozolomide will be administered per label and local prescribing regulations.

Intervention Type

Radiation

Intervention Name(s)

Whole Brain Radiation

Intervention Description

Whole Brain radiation will be administered in 30 fractions.

Primary Outcome Measure Information:

Title

Number and percentage of participants with adverse events

Description

Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG)

Time Frame

Every week for an expected average of 34 weeks

Title

Maximum concentration of ABT-414

Description

Measurement of the maximum concentration of ABT- 414 in the blood

Time Frame

Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks

Title

Number of Dose Limiting Toxicities

Description

Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG)

Time Frame

Every week for an expected average of 34 weeks

Title

Minimum Concentration of ABT-414

Description

Measurement of the minimum concentration of ABT-414 in the blood

Time Frame

Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks

Title

Half-life of ABT-414

Description

Measurement of the clearance of ABT-414

Time Frame

Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks

Secondary Outcome Measure Information:

Title

Biomarker EGFR expression

Description

Assessment of tumor biomarkers that may correlate with efficacy.

Time Frame

At screening and post-study

Title

Progression Free Survival

Description

Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not get worse.

Time Frame

Multiple time points in each cycle, throughout study, and survival information monthly until 1 year after last visit, or the participant becomes lost to follow up, or study termination.

Title

Overall Survival

Description

The overall response rate will be evaluated every 8 weeks at each assessment of disease according to RANO criteria, up to 28 months

Time Frame

Multiple time points in each cycle, throughout study, and survival information monthly until 1 year after last visit, or participant becomes lost to follow up, or study termination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Glioblastoma Multiforme (GBM) 70 or above on Karnofsky Performance Status Adequate bone marrow function Recurrent GBM per RANO criteria Subjects must have confirmed EGFR amplification by central lab Exclusion Criteria: For Subjects with recurrent GBM in Arm B, subject has received prior treatment with bevacizumab, nitrosourea, or has secondary GBM For Subjects with recurrent GBM in Arm C, subject has received prior treatment with bevacizumab, or has secondary GBM Allergies to temozolomide, dacarbazine, IgG containing agents Anti-cancer treatment 28 days prior to study Day 1, except in Arm B expanded cohort temozolomide therapy is allowed Subjects that have had more than one disease recurrence

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Earle Bain, MD

Organizational Affiliation

AbbVie

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

PubMed Identifier

30796037

Citation

Lassman AB, Roberts-Rapp L, Sokolova I, Song M, Pestova E, Kular R, Mullen C, Zha Z, Lu X, Gomez E, Bhathena A, Maag D, Kumthekar P, Gan HK, Scott AM, Guseva M, Holen KD, Ansell PJ, van den Bent MJ. Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma. Clin Cancer Res. 2019 Jun 1;25(11):3259-3265. doi: 10.1158/1078-0432.CCR-18-3034. Epub 2019 Feb 22.

Results Reference

derived

PubMed Identifier

29982805

Citation

Lassman AB, van den Bent MJ, Gan HK, Reardon DA, Kumthekar P, Butowski N, Lwin Z, Mikkelsen T, Nabors LB, Papadopoulos KP, Penas-Prado M, Simes J, Wheeler H, Walbert T, Scott AM, Gomez E, Lee HJ, Roberts-Rapp L, Xiong H, Ansell PJ, Bain E, Holen KD, Maag D, Merrell R. Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial. Neuro Oncol. 2019 Jan 1;21(1):106-114. doi: 10.1093/neuonc/noy091.

Results Reference

derived

PubMed Identifier

29533458

Citation

Goss GD, Vokes EE, Gordon MS, Gandhi L, Papadopoulos KP, Rasco DW, Fischer JS, Chu KL, Ames WW, Mittapalli RK, Lee HJ, Zeng J, Roberts-Rapp LA, Loberg LI, Ansell PJ, Reilly EB, Ocampo CJ, Holen KD, Tolcher AW. Efficacy and safety results of depatuxizumab mafodotin (ABT-414) in patients with advanced solid tumors likely to overexpress epidermal growth factor receptor. Cancer. 2018 May 15;124(10):2174-2183. doi: 10.1002/cncr.31304. Epub 2018 Mar 13.

Results Reference

derived

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Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme

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