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

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ClinicalTrials.gov Identifier: NCT01469793
Recruitment Status : Completed
First Posted : November 10, 2011
Last Update Posted : January 10, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: DMOT4039A Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2011
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

Arms and Interventions
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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 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.
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 years).
 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, 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.
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.


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

Secondary Outcome Measures :
  1. 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) ]
  2. AUC (0-inf) of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) [ Time Frame: 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) ]
  3. AUC (0-inf) of Unconjugated MMAE [ Time Frame: 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) ]
  4. Maximum Observed Concentration (Cmax) of DMOT4039A Total Antibody [ Time Frame: 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) ]
  5. Cmax of acMMAE [ Time Frame: 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) ]
  6. Cmax of Unconjugated MMAE [ Time Frame: 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) ]
  7. Total Clearance (CL) of DMOT4039A Total Antibody [ Time Frame: 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) ]
  8. CL of acMMAE [ Time Frame: 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) ]
  9. Half-life (t1/2) of DMOT4039A Total Antibody [ Time Frame: 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) ]
  10. t1/2 of acMMAE [ Time Frame: 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) ]
  11. t1/2 of Unconjugated MMAE [ Time Frame: 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) ]
  12. Volume of Distribution at Steady State (Vss) of DMOT4039A Total Antibody [ Time Frame: 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) ]
  13. Vss of acMMAE [ Time Frame: 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) ]
  14. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) [ Time Frame: 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) ]
  15. Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: 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) ]
  16. Duration of Objective Response (DOR) According to RECIST v1.1 [ Time Frame: 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) ]
  17. Progression-free Survival (PFS) According to RECIST v1.1 [ Time Frame: 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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01469793


Locations
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United States, Arizona
Phoenix, Arizona, United States, 85259
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Jacksonville, Florida, United States, 32224
United States, Minnesota
Rochester, Minnesota, United States, 55905
Netherlands
Amsterdam, Netherlands, 1081 HV
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01469793    
Other Study ID Numbers: DMO4993g
GP27896 ( Other Identifier: Hoffmann-La Roche )
2011-002713-10 ( EudraCT Number )
First Posted: November 10, 2011    Key Record Dates
Last Update Posted: January 10, 2017
Last Verified: November 2016
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
 Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type