Overview

This trial is active, not recruiting.

Condition non-squamous non-small cell lung cancer
Treatments bevacizumab, carboplatin, dnib0600a
Phase phase 1
Target VEGF
Sponsor Genentech, Inc.
Start date December 2013
End date December 2016
Trial size 33 participants
Trial identifier NCT01995188, GO29006

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.

United States Massachusetts
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
DNIB0600A at an initial dose of 1.2 milligrams per kilogram (mg/kg) will be administered via intravenous (IV) infusion further following a dose-escalation until DLT under consultation of the investigator in combination with Carboplatin fixed dose of area under the curve (AUC)=6 mg/milliliter(mL)*minute (min) administered by IV infusion on Day 1 of a 21-day cycle.
carboplatin
Carboplatin fixed dose of AUC=6 mg/mL*min administered by IV infusion on Day 1 of each 21-day dose escalation and expansion cycles. Carboplatin will be administered for a maximum of 6 cycles or until disease progression or unacceptable toxicity, whichever is first.
dnib0600a
DNIB0600A at an initial dose of 1.2 mg/kg will be administered via IV infusion further following a dose-escalation until DLT under consultation of the investigator on Day 1 of 21 day dose-escalation cycle. RP2D will be administered further in dose-expansion for until disease progression or death, whichever occurs first.
(Experimental)
Recommended phase 2 dose (RP2D) of DNIB0600A administered via IV infusion in combination with Carboplatin, AUC=6 mg/mL*min administered via IV infusion on Day 1 of each 21-day cycle in participants with NSCLC until disease progression or death, whichever occurs first.
dnib0600a
DNIB0600A at an initial dose of 1.2 mg/kg will be administered via IV infusion further following a dose-escalation until DLT under consultation of the investigator on Day 1 of 21 day dose-escalation cycle. RP2D will be administered further in dose-expansion for until disease progression or death, whichever occurs first.
(Experimental)
RP2D of DNIB0600A administered via IV infusion in combination with AUC=6 mg/mL*min administered via IV infusion on Day 1 of each 21-day cycle in participants with PSOC until disease progression or death, whichever occurs first.
carboplatin
Carboplatin fixed dose of AUC=6 mg/mL*min administered by IV infusion on Day 1 of each 21-day dose escalation and expansion cycles. Carboplatin will be administered for a maximum of 6 cycles or until disease progression or unacceptable toxicity, whichever is first.
dnib0600a
DNIB0600A at an initial dose of 1.2 mg/kg will be administered via IV infusion further following a dose-escalation until DLT under consultation of the investigator on Day 1 of 21 day dose-escalation cycle. RP2D will be administered further in dose-expansion for until disease progression or death, whichever occurs first.
(Experimental)
RP2D of DNIB0600A administered via IV infusion in combination with Carboplatin, AUC=6 mg/mL*min and Bevacizumab 15 milligrams per kilogram (mg/kg) administered via IV infusion on Day 1 of each 21-day cycle in participants with PSOC until disease progression or death, whichever occurs first.
bevacizumab Avastin
Bevacizumab 15 milligrams per kilogram (mg/kg) administered via IV infusion on Day 1 of each 21-day cycle until disease progression or death, whichever occurs first.
carboplatin
Carboplatin fixed dose of AUC=6 mg/mL*min administered by IV infusion on Day 1 of each 21-day dose escalation and expansion cycles. Carboplatin will be administered for a maximum of 6 cycles or until disease progression or unacceptable toxicity, whichever is first.
dnib0600a
DNIB0600A at an initial dose of 1.2 mg/kg will be administered via IV infusion further following a dose-escalation until DLT under consultation of the investigator on Day 1 of 21 day dose-escalation cycle. RP2D will be administered further in dose-expansion for until disease progression or death, whichever occurs first.

Primary Outcomes

Measure
Number of Participants with Dose-limiting Toxicities (DLTs)
time frame: 21 days
Number of Participants with Adverse events (AE) and Serious Adverse Events (SAEs)
time frame: Day 1 until 30 days after the last-infusion (up to approximately 3 years)
Number of Participants with Anti-DNIB0600A Antibodies
time frame: 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
time frame: 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)
Maximum Observed Plasma Concentration (Cmax)
time frame: 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)
Minimum Observed Plasma Trough Concentration (Cmin)
time frame: 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)
Systemic Clearance (CL)
time frame: 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)
Volume of Distribution at Steady State (Vss)
time frame: 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)
Plasma Decay Half-Life (t1/2)
time frame: 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)
Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
time frame: 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)
Duration of Objective Response Rate as Assessed by RECIST v1.1
time frame: 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)
Progression Free Survival (PFS) as Assessed by RECIST v1.1
time frame: 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)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Genentech, Inc..