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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01995188
First received: November 15, 2013
Last updated: September 13, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Non-Squamous Non-Small Cell Lung Cancer
Drug: Bevacizumab
Drug: Carboplatin
Drug: DNIB0600A
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: December 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation Cohort: DNIB0600A+Carboplatin
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.
Drug: 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.
Drug: 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: NSCLC Dose Expansion Cohort: DNIB0600A+Carboplatin
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.
Drug: 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: PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin
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.
Drug: 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.
Drug: 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: PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin+Bevacizumab
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.
Drug: Bevacizumab
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.
Other Name: Avastin
Drug: 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.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01995188

Locations
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02115
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01995188     History of Changes
Other Study ID Numbers: GO29006 
Study First Received: November 15, 2013
Last Updated: September 13, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Ovarian Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Bevacizumab
Carboplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 27, 2016