Clinical trial NCT01995188: A Study to Evaluate the Safety and Pharmacology of DNIB0600A in Participants With Platinum-Sensitive Ovarian Cancer or Non-Squamous Non-small Cell Lung Cancer
Official title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of DNIB0600A in Combination With Carboplatin (With or Without Bevacizumab) in Patients With Platinum-Sensitive Ovarian Cancer or Non-Squamous Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Squamous Non-Small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-26
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This open-label, multicenter, phase 1b study will evaluate the safety and pharmacokinetics of DNIB0600A in participants with platinum-sensitive ovarian cancer (PSOC) or Non-Squamous Non-small Cell Lung Cancer (NSCLC). The maximum tolerated dose of intravenously infused DNIB0600A in combination with carboplatin will be determined in escalating dose cohorts. The combination of DNIB0600A and carboplatin will then be evaluated with and without bevacizumab \[Avastin\] in three dose expansion cohorts.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
* Histologically documented epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that is platinum sensitive.
* PSOC (i.e., epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer) with documented radiographic progression or relapse within 6 to 18 months of most recent platinum-based chemotherapy.
* Female participants of childbearing potential must use effective contraception as defined by study protocol and cannot be pregnant or breastfeeding.

NSCLC-specific Inclusion Criteria:

* Histological documentation of incurable, locally advanced, or metastatic non-squamous
* NSCLC that has progressed on prior treatment
* Not more than 2 prior regimens in the metastatic setting, including one prior cytotoxic regimen and one prior non-cytotoxic regimen (prior treatment with adjuvant therapy within 6 months of recurrence is considered a treatment regimen in the metastatic setting).
* For participants with a documented epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement, one additional line of non-cytotoxic prior treatment will be permitted provided the therapy is a targeted agent against the EGFR mutation or ALK rearrangement.
* For participants with lung cancer, centrally confirmed high expression of a sodium-dependent phosphate transporter (NaPi2b) by immunohistochemistry (IHC) is required (i.e., IHC 2+ or 3+).

Exclusion Criteria:

* Anti-tumor therapy of any kind or major surgery within 4 weeks prior to Day 1.
* For ovarian cancer participants only, platinum-based chemotherapy within 6 months prior to Day 1.
* For ovarian cancer participants only, platinum treatment with more than two platinum-based chemotherapy regiments or more than four anti-cancer regimens, overall, for the treatment of ovarian cancer.
* Palliative radiation within 2 weeks prior to Day 1.
* Toxicity (except alopecia and anorexia) from prior therapy or neuropathy of grades \> 1.
* Evidence of any significant disease or condition that could affect compliance with the protocol or interpretation of results.
* Known active infection (except fungal nail infections).
* History of liver disease or human immunodeficiency virus (HIV).
* Other malignancy within the last 5 years, except for adequately treated or controlled carcinoma in situ of the cervix or skin cancer or primary endometrial cancer of stage \</= 1B.
* Untreated or active central nervous system (CNS) metastases.
* Prior treatment with NaPi2b- targeted therapy.

Bevacizumab-Specific Exclusion Criteria (for Participants in Second Ovarian

Expansion Cohort Only):

* Inadequately controlled hypertension or history of hypertensive crisis or encephalopathy.
* History of heart problems or thrombosis within 6 months prior to study start.
* History of stroke within 6 months prior to study enrollment.
* History of significant vascular disease.
* History of expectoration of blood within 1 month prior to study start or blood clotting problems.
* Core biopsy or other minor surgical procedure within 7 days prior to study start
* Serious and non-healing wound, active ulcer, or untreated bone fracture.

Primary outcomes:
measure: Number of Participants with Dose-limiting Toxicities (DLTs)
timeFrame: 21 days
measure: Number of Participants with Adverse events (AE) and Serious Adverse Events (SAEs)
timeFrame: Day 1 until 30 days after the last-infusion (up to approximately 3 years)
measure: Number of Participants with Anti-DNIB0600A Antibodies
timeFrame: Pre-infusion (0 hour) at Day 1 of Cycle 1, 2, 3, 4 (each cycle of 21 days), 30 days after last infusion (up to approximately 3 years)
Secondary outcomes:
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] of DNIB0600A
timeFrame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
measure: Minimum Observed Plasma Trough Concentration (Cmin)
timeFrame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
measure: Systemic Clearance (CL)
timeFrame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
measure: Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
timeFrame: From screening thereafter every 2 cycles (from Cycle 2 to Cycle 16) or every 4 cycles (from Cycle 10) until disease progression or death (up to approximately 3 years)
measure: Duration of Objective Response Rate as Assessed by RECIST v1.1
timeFrame: From screening thereafter every 2 cycles (from Cycle 2 to Cycle 16) or every 4 cycles (from Cycle 10) until disease progression or death (up to approximately 3 years)
measure: Progression Free Survival (PFS) as Assessed by RECIST v1.1
timeFrame: Day 1 to the first occurrence of disease progression or death within 30 days of the last administration of study drug, whichever occurs first (up to approximately 3 years)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Inst.
state: Massachusetts
city: Oklahoma City
country: United States
facility: The University of Oklahoma
state: Oklahoma
city: Nashville
country: United States
facility: The Sarah Cannon Research Inst
state: Tennessee
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: