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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02219724




Registration number
NCT02219724
Ethics application status
Date submitted
15/08/2014
Date registered
19/08/2014
Date last updated
5/02/2020

Titles & IDs
Public title
A Study to Assess Safety and Pharmacokinetics of MOXR0916 in Participants With Locally Advanced or Metastatic Solid Tumors
Scientific title
A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MOXR0916 Administered Intravenously as a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
2014-001474-34
Secondary ID [2] 0 0
GO29313
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MOXR0916

Experimental: MOXR0916: Dose Escalation Stage - Participants in different cohorts (according to MOXR0916 dose received) will receive escalating doses of MOXR0916 to determine the MTD or maximum administered dose (MAD) for 21 to 42 days.

Experimental: MOXR0916: Expansion Stage - Participants in different cohorts (according to different cancer types, prior therapy and mandatory procedures on study) will receive MOXR0916 at the highest dose level that has already been deemed to be tolerable in the dose escalation stage until disease progression, loss of clinical benefit or unacceptable toxicity, whichever occurred first (approximately up to 3 years).


Treatment: Drugs: MOXR0916
MOXR0916 will be administered as intravenous infusion on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Day 1 Up to Day 21 or 42
Primary outcome [2] 0 0
Percentage of Participants With Adverse Events (AEs) by Severity as Graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
Timepoint [2] 0 0
Baseline up to 90 days after the last dose of study treatment, or until the initiation of another systemic anti-cancer therapy, whichever occurs first (approximately up to 3 years)
Secondary outcome [1] 0 0
Maximum Tolerated Dose (MTD) of MOXR0916
Timepoint [1] 0 0
Baseline up to 21 to 42 days
Secondary outcome [2] 0 0
Recommended Phase II Dose of MOXR0916
Timepoint [2] 0 0
Baseline up to 21 to 42 days
Secondary outcome [3] 0 0
Percentage of Participants With Anti-MOXR0916 Antibodies
Timepoint [3] 0 0
Pre-dose (Hour [Hr] 0) on Day (D) 1 of Cycles (Cy) 1,2,3,4,8,12,16, & then every 8 Cy up to treatment discontinuation visit (TDV) (up to approximately 3 years) (1 Cy=21 days), thereafter every 30 days for up to 120 days after treatment discontinuation
Secondary outcome [4] 0 0
Number of Cycles of MOXR0916 Treatment Received
Timepoint [4] 0 0
Baseline up to approximately 3 years
Secondary outcome [5] 0 0
Mean MOXR0916 Dose Administered During Study
Timepoint [5] 0 0
Baseline up to approximately 3 years
Secondary outcome [6] 0 0
Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of MOXR0916
Timepoint [6] 0 0
Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days
Secondary outcome [7] 0 0
Maximum Observed Serum Concentration (Cmax) of MOXR0916
Timepoint [7] 0 0
Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days
Secondary outcome [8] 0 0
Minimum Observed Serum Concentration (Cmin) of MOXR0916
Timepoint [8] 0 0
Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days
Secondary outcome [9] 0 0
Serum Clearance (CL/F) of MOXR0916
Timepoint [9] 0 0
Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days
Secondary outcome [10] 0 0
Apparent Volume of Distribution at Steady State (Vss) of MOXR0916
Timepoint [10] 0 0
Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days
Secondary outcome [11] 0 0
Percentage of Participants With Objective Response as Determined Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Timepoint [11] 0 0
Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years)
Secondary outcome [12] 0 0
Duration of Objective Response (DOR) as Determined Using RECIST v1.1
Timepoint [12] 0 0
Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years)
Secondary outcome [13] 0 0
Progression-free Survival (PFS) as Determined Using RECIST v1.1
Timepoint [13] 0 0
Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years)
Secondary outcome [14] 0 0
Percentage of Participants With Objective Response as Determined Using Modified RECIST
Timepoint [14] 0 0
Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years)
Secondary outcome [15] 0 0
DOR as Determined Using Modified RECIST
Timepoint [15] 0 0
Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years)
Secondary outcome [16] 0 0
PFS as Determined Using Modified RECIST
Timepoint [16] 0 0
Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years)
Secondary outcome [17] 0 0
Overall Survival (OS)
Timepoint [17] 0 0
Baseline until death, loss to follow-up, withdrawal of consent, or study termination by the Sponsor (approximately up to 3 years)

Eligibility
Key inclusion criteria
- Histologic documentation of locally advanced, recurrent or metastatic incurable solid
malignancy that has progressed after all available standard therapy or for which
standard therapy has proven to be ineffective or intolerable, or is considered
inappropriate

- Confirmed availability of representative tumor specimens in paraffin blocks/unstained
slides

- Measurable disease per RECIST v1.1

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Adequate hematologic and end organ function

- For female participants of childbearing potential, agreement to use highly effective
form(s) of contraception and to continue its use for 6 months after the last dose of
MOXR0916
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy,
within 3 weeks prior to initiation of study treatment (hormonal therapy with
gonadotropin-releasing hormone agonists or antagonists for prostate cancer and
palliative radiotherapy greater than (>) 2 weeks prior to Cycle 1, Day 1 are allowed)

- Eligibility based on prior treatment with immunomodulatory agents depends on the
mechanistic class of the drug and the cohort for which the participant is being
considered

- Adverse events from prior anti-cancer therapy that have not resolved to Grade less
than or equal to (</=) 1 except for alopecia or endocrinopathy managed with
replacement therapy

- Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases

- Leptomeningeal disease

- Malignancies other than disease under study within 5 years

- History of autoimmune disease

- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia, or evidence of active pneumonitis on screening chest computed
tomography (CT) scan; history of radiation pneumonitis in the radiation field
(fibrosis) is permitted

- Positive test for human immunodeficiency virus infection

- Active hepatitis B or active hepatitis C

- Severe infections within 4 weeks or signs or symptoms of infection within 2 weeks
prior to Cycle 1

- Prior allogeneic bone marrow transplantation or prior solid organ transplantation

- Significant cardiovascular disease

- Known clinically significant liver disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/08/2019
Sample size
Target
Accrual to date
Final
174
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussels
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Belgium
State/province [13] 0 0
Wilrijk
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul
Country [18] 0 0
Spain
State/province [18] 0 0
Navarra
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Spain
State/province [21] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human, Phase 1, open-label, multicenter, dose-escalation study designed to
evaluate the safety, tolerability, and pharmacokinetics of MOXR0916 administered
intravenously in participants with locally advanced or metastatic solid tumors that have
progressed after all available standard therapy or for which standard therapy has proven to
be ineffective or intolerable, or is considered inappropriate. This study will consist of a
screening period, an initial treatment period, a re-treatment period (for participants who
discontinue MOXR0916 after demonstration of prolonged clinical benefit), and a post-treatment
follow-up period. Participants will be enrolled in two stages: a dose-escalation stage and an
expansion stage. The planned duration of the study is approximately 3 years.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02219724
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02219724