Back to resultsSafety and Pharmacokinetics of Escalating Doses of DNIB0600A in Participants With Non-Small Cell Lung Cancer (NSCLC) and Platinum Resistant Ovarian Cancer
Primary Purpose
Non-Small Cell Lung Cancer, Ovarian Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DNIB0600A
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer, Ovarian Cancer
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologic documentation of incurable, locally advanced or metastatic disease that has failed prior chemotherapy and for which no standard therapy exists, including the following: non-squamous NSCLC or non-mucinous and platinum-resistant ovarian cancer
- Availability and willingness to provide an adequate archival sample of tumor
- Measurable disease
- For fertile men or women of childbearing potential, documented willingness to use a highly effective means of contraception
Exclusion Criteria:
- Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy within 4 weeks prior to study treatment
- Major surgical procedure within 4 weeks prior to study treatment
- Known active bacterial, viral, fungal, mycobacterial, or other infection (including human immunodeficiency virus [HIV] and atypical mycobacterial disease, but excluding fungal infections of the nail beds)
- Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Untreated or active central nervous system (CNS) metastases
- Requirement for supplemental oxygen to carry out activities of daily living
- 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 participant at high risk from treatment complications
- Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture
- For participants in the second NSCLC cohort expansion, not more than two prior regimens in the metastatic setting
- Pregnancy or breast-feeding
Sites / Locations
- HonorHealth Research Institute - Pima Center
- Smilow Cancer Hospital at Yale New Haven
- Sarah Cannon Research Inst.
- Univ of Texas SW Medical Ctr
- Hospital del Mar; Servicio de Oncologia
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
- Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose Escalation Cohort (DNIB0600A)
Expansion Cohort (DNIB0600A)
Arm Description
Participants will receive IV infusions of DNIB0600A at doses ranging from 0.2 milligrams/kilogram (mg/kg) to 2.8 mg/kg q3w until dose-limiting toxicity (DLT) is reached, or up to 28 cycles.
Participants will receive 2.4 mg/kg, by IV infusion, of DNIB0600A q3w for up to 26 cycles.
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events (AEs)
An AE is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of causality.
Secondary Outcome Measures
Cmax of DNIB0600A for Antibody-Conjugated Monomethyl Auristatin E (acMMAE), Total Antibody, and Unconjugated Monomethyl Auristatin E (MMAE)
Cmax is the peak concentration of a substance in blood serum.
Percentage of Participants with Antibody Formation to DNIB0600A
Serum samples will be analyzed to assess the prevalence of anti-drug antibodies (ADAs) at baseline and the incidence of post-baseline ADAs in each treatment group.
Percentage of Participants with Objective Response (OR)
OR is defined as a complete or partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum on study. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
Duration of Objective Response (DOR)
OR is defined as a complete or partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum on study. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01363947
Brief Title
Safety and Pharmacokinetics of Escalating Doses of DNIB0600A in Participants With Non-Small Cell Lung Cancer (NSCLC) and Platinum Resistant Ovarian Cancer
Official Title
A Phase I, Open-Label Study of the Safety and Pharmacokinetics of Escalating Doses of DNIB0600A in Patients With Non-Small Cell Lung Cancer and Platinum-Resistant Ovarian Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 14, 2011 (Actual)
Primary Completion Date
June 3, 2016 (Actual)
Study Completion Date
June 3, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Study DNB4987g is a Phase I, multicenter, open label, dose-escalation study of DNIB0600A administered as a single agent by intravenous (IV) infusion every three weeks (q3w) to participants with non-squamous NSCLC or non-mucinous, platinum-resistant ovarian cancer. The study will be conducted in two cohorts: Dose-escalation cohort and Expansion cohort.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, 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
87 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation Cohort (DNIB0600A)
Arm Type
Experimental
Arm Description
Participants will receive IV infusions of DNIB0600A at doses ranging from 0.2 milligrams/kilogram (mg/kg) to 2.8 mg/kg q3w until dose-limiting toxicity (DLT) is reached, or up to 28 cycles.
Arm Title
Expansion Cohort (DNIB0600A)
Arm Type
Experimental
Arm Description
Participants will receive 2.4 mg/kg, by IV infusion, of DNIB0600A q3w for up to 26 cycles.
Intervention Type
Drug
Intervention Name(s)
DNIB0600A
Intervention Description
Several dose levels will be evaluated for DNIB0600A administered via IV infusion on Day 1 of each 21-day cycle until disease progression.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs)
Description
An AE is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of causality.
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Cmax of DNIB0600A for Antibody-Conjugated Monomethyl Auristatin E (acMMAE), Total Antibody, and Unconjugated Monomethyl Auristatin E (MMAE)
Description
Cmax is the peak concentration of a substance in blood serum.
Time Frame
Day 21
Title
Percentage of Participants with Antibody Formation to DNIB0600A
Description
Serum samples will be analyzed to assess the prevalence of anti-drug antibodies (ADAs) at baseline and the incidence of post-baseline ADAs in each treatment group.
Time Frame
Up to approximately 84 weeks
Title
Percentage of Participants with Objective Response (OR)
Description
OR is defined as a complete or partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum on study. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
Time Frame
Up to approximately 84 weeks
Title
Duration of Objective Response (DOR)
Description
OR is defined as a complete or partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum on study. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
Time Frame
Up to approximately 84 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Histologic documentation of incurable, locally advanced or metastatic disease that has failed prior chemotherapy and for which no standard therapy exists, including the following: non-squamous NSCLC or non-mucinous and platinum-resistant ovarian cancer
Availability and willingness to provide an adequate archival sample of tumor
Measurable disease
For fertile men or women of childbearing potential, documented willingness to use a highly effective means of contraception
Exclusion Criteria:
Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy within 4 weeks prior to study treatment
Major surgical procedure within 4 weeks prior to study treatment
Known active bacterial, viral, fungal, mycobacterial, or other infection (including human immunodeficiency virus [HIV] and atypical mycobacterial disease, but excluding fungal infections of the nail beds)
Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
Untreated or active central nervous system (CNS) metastases
Requirement for supplemental oxygen to carry out activities of daily living
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 participant at high risk from treatment complications
Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture
For participants in the second NSCLC cohort expansion, not more than two prior regimens in the metastatic setting
Pregnancy or breast-feeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Maslyar, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
HonorHealth Research Institute - Pima Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Smilow Cancer Hospital at Yale New Haven
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Sarah Cannon Research Inst.
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Univ of Texas SW Medical Ctr
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Hospital del Mar; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Univ Vall d'Hebron; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28007
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Safety and Pharmacokinetics of Escalating Doses of DNIB0600A in Participants With Non-Small Cell Lung Cancer (NSCLC) and Platinum Resistant Ovarian Cancer
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