A Study Of DMOT4039A In Participants With Unresectable Pancreatic Or Platinum-Resistant Ovarian Cancer

Study Overview

A Study of DMOT4039A in Participants With Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer

This multicenter, open-label, dose-escalating study will assess the safety, tolerability, and pharmacokinetics of DMOT4039A in participants with unresectable pancreatic or platinum-resistant ovarian cancer. Cohorts of participants will receive multiple ascending intravenous doses of DMOT4039A.

N/A

Ovarian Cancer

DRUG: DMOT4039A

DMO4993g
GP27896 (OTHER Identifier) (OTHER: Hoffmann-La Roche)
2011-002713-10 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-11-07	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2017-01-06
First Submitted that Met QC Criteria 2011-11-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2017-01-10
First Posted (ESTIMATED) 2011-11-10	Results First Posted N/A	Last Verified 2016-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: DMOT4039A Q3W: Dose Escalation Participants in different cohorts will receive DMOT4039A at various escalating dose levels, starting with 0.2 milligrams per kilogram (mg/kg), as intravenous infusion every 3 weeks (Q3W) to determine the maximum tolerated dose (MTD) of DMOT4039A for until	DRUG: DMOT4039A DMOT4093A will be administered by intravenous infusion on either a Q3W or a Q1W dosing schedule, in 21-day cycles.
EXPERIMENTAL: DMOT4039A Q3W: Dose Expansion Participants will receive DMOT4039A at recommended phase 2 dose (RP2D) for Q3W dosing schedule as intravenous infusion Q3W until disease progression, loss of clinical benefit or unacceptable toxicity, whichever occurred first (up to approximately 2.5 year	DRUG: DMOT4039A DMOT4093A will be administered by intravenous infusion on either a Q3W or a Q1W dosing schedule, in 21-day cycles.
EXPERIMENTAL: DMOT4039A Q1W: Dose Escalation Participants in different cohorts will receive DMOT4039A at various escalating dose levels, starting with a dose 33% of MTD for Q3W dosing schedule, as intravenous infusion every week (Q1W) to determine the MTD of DMOT4039A for until disease progression,	DRUG: DMOT4039A DMOT4093A will be administered by intravenous infusion on either a Q3W or a Q1W dosing schedule, in 21-day cycles.
EXPERIMENTAL: DMOT4039A Q1W: Dose Expansion Participants will receive DMOT4039A at RP2D for Q1W dosing schedule as intravenous infusion Q1W until disease progression, loss of clinical benefit or unacceptable toxicity, whichever occurred first (up to approximately 2.5 years).	DRUG: DMOT4039A DMOT4093A will be administered by intravenous infusion on either a Q3W or a Q1W dosing schedule, in 21-day cycles.

Primary Outcome Measures	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of DMOT4039A		Days 1 to 21 of Cycle 1 (1 cycle=21 days)
Number of Participants With Dose-Limiting Toxicities (DLTs)		Days 1 to 21 of Cycle 1 (1 cycle=21 days)
Recommended Phase 2 Dose (RP2D) of DMOT4039A		Days 1 to 21 of Cycle 1 (1 cycle=21 days)

Secondary Outcome Measures	Measure Description	Time Frame
Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-inf]) of DMOT4039A Total Antibody		Q3W: Pre-infusion (0 hours [hrs]), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion, 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
AUC (0-inf) of Antibody-Conjugated Monomethyl Auristatin E (acMMAE)		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
AUC (0-inf) of Unconjugated MMAE		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Maximum Observed Concentration (Cmax) of DMOT4039A Total Antibody		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Cmax of acMMAE		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Cmax of Unconjugated MMAE		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Total Clearance (CL) of DMOT4039A Total Antibody		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
CL of acMMAE		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Half-life (t1/2) of DMOT4039A Total Antibody		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
t1/2 of acMMAE		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
t1/2 of Unconjugated MMAE		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Volume of Distribution at Steady State (Vss) of DMOT4039A Total Antibody		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Vss of acMMAE		Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)		Baseline (pre-infusion [0 hrs] on Day 1 Cycle 1); Post-Baseline (assessed at pre-infusion [0 hrs] on Day 1 of Cycles 2-4 and at study completion/early termination [up to 30 days after Cycle 32]) (1 cycle=21 days)
Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)		Baseline up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up to 30 days after Cycle 32]) (1 cycle=21 days)
Duration of Objective Response (DOR) According to RECIST v1.1		From the date of initial PR or CR up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up to 30 days after Cycle 32]) (1 cycle=21 days)
Progression-free Survival (PFS) According to RECIST v1.1		Day 1 up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up 30 days after Cycle 32]) (1 cycle=21 days)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Histologically documented, incurable, locally advanced or metastatic disease for which no standard therapy exists, consisting of one of the following: Unresectable pancreatic ductal adenocarcinoma or platinum-resistant ovarian cancer
Measureable disease, defined as at least one bi-dimensionally measurable non-lymph node lesion greater than or equal to (>/=) 1 centimeter (cm) in long-axis diameter on spiral computed tomography (CT) scan or at least one bi-dimensionally measurable lymph node measuring >/= 1.5 cm in short-axis diameter on spiral CT scan
Adequate hematological, renal and liver function

Treatment with anti-tumor therapy, including chemotherapy, biologic, experimental or hormonal therapy, within 4 weeks prior to Day 1
Known active infection
Current Grade >/= 2 toxicity (except for alopecia, anorexia and fatigue) from prior therapy or Grade >/= 2 neuropathy
Untreated or active cerebral nervous system metastases
Pregnant or breastfeeding women

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Clinical Trials, Hoffmann-La Roche

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Clinical Trial Record