Safety and Pharmacokinetics of DMUC5754A Administered Intravenously to Patients With Platinum-Resistant Ovarian Cancer or Unresectable Pancreatic Cancer

A Phase I, Open-Label, Dose Escalation Study of the Safety and Pharmacokinetics of DMUC5754A Administered Intravenously to Patients With Platinum-Resistant Ovarian Cancer or Unresectable Pancreatic Cancer

This is a Phase I, multi-center, open-label, dose-escalation study of DMUC5754A administered as a single agent by intravenous (IV) infusion to patients with platinum-resistant ovarian cancer or unresectable pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer, Pancreatic Cancer
• Intervention / Treatment: Drug: DMUC5754A

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
    • Boston, Massachusetts, United States, 02115
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Tennessee
    • Nashville, Tennessee, United States, 37203

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Life expectancy of at least 12 weeks
• Documented willingness to use an effective means of contraception for women of childbearing potential
• Measurable disease with at least one lesion that can be accurately measured in at least one dimension

Inclusion Criteria Specific to Patients with Ovarian Cancer:

• Advanced, epithelial ovarian, primary peritoneal, or fallopian tube cancer that has progressed or relapsed during or within 6 months of the most recent treatment with a platinum-containing chemotherapy regimen, and for which no standard therapy exists
• For patients in the dose-expansion cohort of the study only, no more than two prior chemotherapy regimens for the treatment of platinum-resistant ovarian cancer

Inclusion Criteria Specific to Patients with Pancreatic Cancer:

• Incurable, locally advanced, or metastatic disease for which no standard therapy exists, consisting of unresectable pancreatic ductal adenocarcinoma, including recurrence of previously-resected disease that is considered unresectable with curative intent
• No more than one chemotherapy regimen (approved or experimental) administered in the metastatic setting

Exclusion Criteria:

• Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy within 4 weeks prior to Day 1
• Palliative radiation to bone metastases within 2 weeks prior to Day 1
• Major surgical procedure within 4 weeks prior to Day 1
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including HIV and atypical mycobacterial disease, but excluding fungal infections of the nail beds)
• Current Grade >1 toxicity (except alopecia and anorexia) from prior therapy or Grade >1 neuropathy from any cause
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria: evaluable or measurable disease outside the CNS, radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study, and the screening CNS radiographic study is >= 8 weeks since completion of radiotherapy and >= 4 weeks since the discontinuation of corticosteroids and anticonvulsants.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmias, and unstable angina); nervous system, pulmonary (including obstructive pulmonary disease and history of symptomatic bronchospasm), renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture
• Pregnancy or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: DMUC5754A; Escalating intravenous dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose-limiting toxicities (DLTs)	Up to 21 days
Nature of dose-limiting toxicities (DLTs) graded per NCI CTCAE v4.0	Up to 21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events	Up to 1 year
Nature of adverse events graded per NCI CTCAE v4.0	Up to 1 year
Severity of adverse events	Up to 1 year
Area under the concentration-time curve	up to 1 year
Maximum concentrations	up to 1 year
Minimum concentrations	up yo 1 year
Clearance	up to 1 year
Half-life	up to 1 year
Volume of distribution	up to 1 year

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Liu JF, Moore KN, Birrer MJ, Berlin S, Matulonis UA, Infante JR, Wolpin B, Poon KA, Firestein R, Xu J, Kahn R, Wang Y, Wood K, Darbonne WC, Lackner MR, Kelley SK, Lu X, Choi YJ, Maslyar D, Humke EW, Burris HA. Phase I study of safety and pharmacokinetics of the anti-MUC16 antibody-drug conjugate DMUC5754A in patients with platinum-resistant ovarian cancer or unresectable pancreatic cancer. Ann Oncol. 2016 Nov;27(11):2124-2130. doi: 10.1093/annonc/mdw401.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 13, 2011
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 15, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Ovarian Neoplasms; Pancreatic Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: DGR4980g; GO00766 (Other Identifier: Hoffmann-La Roche)