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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

DMOT4039A

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

DMOT4039A Q3W: Dose Escalation

DMOT4039A Q3W: Dose Expansion

DMOT4039A Q1W: Dose Escalation

DMOT4039A Q1W: Dose Expansion

Arm Description

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 disease progression, loss of clinical benefit or unacceptable toxicity, whichever occurred first (up to approximately 2.5 years).

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 years).

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, loss of clinical benefit or unacceptable toxicity, whichever occurred first (up to approximately 2.5 years).

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).

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of DMOT4039A

Number of Participants With Dose-Limiting Toxicities (DLTs)

Recommended Phase 2 Dose (RP2D) of DMOT4039A

Secondary Outcome Measures

Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-inf]) of DMOT4039A Total Antibody

AUC (0-inf) of Antibody-Conjugated Monomethyl Auristatin E (acMMAE)

AUC (0-inf) of Unconjugated MMAE

Maximum Observed Concentration (Cmax) of DMOT4039A Total Antibody

Cmax of acMMAE

Cmax of Unconjugated MMAE

Total Clearance (CL) of DMOT4039A Total Antibody

CL of acMMAE

Half-life (t1/2) of DMOT4039A Total Antibody

t1/2 of acMMAE

t1/2 of Unconjugated MMAE

Volume of Distribution at Steady State (Vss) of DMOT4039A Total Antibody

Vss of acMMAE

Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)

Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Duration of Objective Response (DOR) According to RECIST v1.1

Progression-free Survival (PFS) According to RECIST v1.1

Full Information

NCT ID

NCT01469793

First Posted

November 7, 2011

Last Updated

January 6, 2017

Sponsor

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01469793

Brief Title

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

Official Title

A Phase I, Open Label Study of the Safety and Pharmacokinetics of Escalating Doses of DMOT4039A in Patients With Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

November 2011 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genentech, Inc.

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

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

Ovarian Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

71 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DMOT4039A Q3W: Dose Escalation

Arm Type

Experimental

Arm Description

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 disease progression, loss of clinical benefit or unacceptable toxicity, whichever occurred first (up to approximately 2.5 years).

Arm Title

DMOT4039A Q3W: Dose Expansion

Arm Type

Experimental

Arm Description

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 years).

Arm Title

DMOT4039A Q1W: Dose Escalation

Arm Type

Experimental

Arm Description

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, loss of clinical benefit or unacceptable toxicity, whichever occurred first (up to approximately 2.5 years).

Arm Title

DMOT4039A Q1W: Dose Expansion

Arm Type

Experimental

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

DMOT4039A

Intervention Description

DMOT4093A will be administered by intravenous infusion on either a Q3W or a Q1W dosing schedule, in 21-day cycles.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) of DMOT4039A

Time Frame

Days 1 to 21 of Cycle 1 (1 cycle=21 days)

Title

Number of Participants With Dose-Limiting Toxicities (DLTs)

Time Frame

Days 1 to 21 of Cycle 1 (1 cycle=21 days)

Title

Recommended Phase 2 Dose (RP2D) of DMOT4039A

Time Frame

Days 1 to 21 of Cycle 1 (1 cycle=21 days)

Secondary Outcome Measure Information:

Title

Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-inf]) of DMOT4039A Total Antibody

Time Frame

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)

Title

AUC (0-inf) of Antibody-Conjugated Monomethyl Auristatin E (acMMAE)

Time Frame