A Study of Carboplatin and Pemetrexed Plus Demcizumab (OMP-21M18) in Subjects With Non-Squamous Non-Small Cell Lung Cancer

NCT01189968 | Completed Phase 1 DMC

• 1 other identifier: M18-004
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 7

Brief Summary

The purpose of this study is to test the safety and determine the optimal dose of a new drug, demcizumab (OMP-21M18), when given in combination with carboplatin and pemetrexed, a standard drug treatment regimen for non-squamous non-small cell lung cancer (NSCLC). Participants must not have received prior chemotherapy for their NSCLC. Demcizumab is a humanized monoclonal antibody (a protein made in the laboratory) developed to target cancer stem cells. The way the body handles demcizumab will also be investigated. Up to 50 subjects will be enrolled at up to 8 centers in Australia, New Zealand, and Spain. Up to 28 days (4 weeks) prior to treatment you will undergo testing to determine your eligibility to take part in this study, and then if enrolled in the study you will receive intravenous (in the vein) infusions of the demcizumab, carboplatin, and pemetrexed administered on the same day, every 21 days for 4 cycles, or until it has been shown that your cancer has progressed. If your physician decides to delay treatment with one of the agents due to side effects, the other agents may still be administered as scheduled. After 4 cycles, if you have stable or improved disease, you will continue to receive pemetrexed once every 21 days as maintenance therapy. You will undergo assessments every 8 weeks to determine the status of your disease.

Conditions

Non Small Cell Lung Cancer

Keywords

Phase 1,; dose escalation,; histologically; confirmed; malignancy; metastatic

Outcome Measures

Primary Outcomes (1)

• To the determine the maximum tolerated dose of demcizumab (OMP-21M18) plus carboplatin and pemetrexed

  When each patient in the dose cohort reaches Day 56

Secondary Outcomes (5)

• To determine the safety of carboplatin and pemetrexed plus demcizumab (OMP-21M18)

  until treatment termination plus 30 days

• To determine the rates of immunogenicity of carboplatin and pemetrexed plus demcizumab (OMP-21M18)

  Up to 12 weeks post treatment termination

• To determine the preliminary efficacy of carboplatin and pemetrexed plus demcizumab (OMP-21M18)

  Until disease progression

• To determine population pharmacokinetics

  Day 21 and 63

• To determine the exploratory biomarker changes of carboplatin and pemetrexed plus demcizumab (OMP-21M18)

  Until Day 112

Study Arms (2)

Carboplatin and Pemetrexed plus demcizumab

EXPERIMENTAL

Carboplatin and Pemetrexed plus demcizumab

Drug: Demcizumab

Pemetrexed plus demcizumab

EXPERIMENTAL

Pemetrexed plus demcizumab

Drug: Demcizumab

Interventions

Demcizumab DRUG

The 6 subjects in the first cohort will receive demcizumab 5 mg/kg once every 3 weeks; the 6 subjects in the subsequent cohort will be treated with 10 mg/kg once every 3 weeks; and the 6 subjects in the final cohort will be treated with 15 mg/kg once every 3 weeks. A Data Safety Monitoring Board (DSMB) will review the data for the 6 subjects in each dose cohort after the last subject in that cohort has been on study for 56 days and then decide whether it is safe to escalate to the next highest dose cohort. Once the dose-escalation portion of the study has been completed, 14 additional subjects will be treated at the highest dose level that the DSMB deems as safe.

Also known as: OMP-21M18

Carboplatin and Pemetrexed plus demcizumab; Pemetrexed plus demcizumab

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically confirmed unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC. Subjects may not have received prior therapy for their unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC. Subjects may have received prior surgery, prior radiotherapy, and/or prior neoadjuvant or adjuvant chemotherapy (they must have discontinued prior neoadjuvant or adjuvant chemotherapy at least 12 weeks prior to study entry).
• Age \>21 years
• ECOG performance status \<2 (see Appendix B)
• Life expectancy of more than 3 months
• Subjects must have normal organ and marrow function as defined below:
• Leukocytes \>3.5 x 109/L
• Absolute neutrophil count \>1.25 x 109/L Hemoglobin \>100 g/L
• Platelets \>125 X 109/L
• Total bilirubin \<2 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \<5 X institutional ULN
• Alkaline phosphatase \<5 X institutional ULN
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within institutional ULN
• Calculated creatinine clearance \>60 mL/min using the Cockcroft and Gault formula as follows:
• Creatinine clearance (mL/min) = (140 - age) x ideal body weight \[kg\] 0.814 x serum creatinine \[μmol/L\] For women multiply the value from the equation above by 0.85. Where age is in years, weight is in kg, and serum creatinine is in μmol/L.
• Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drugs. Men must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drugs. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of the study drugs, the Investigator should be informed immediately.

You may not qualify if:

• Subjects who meet any of the following criteria will not be eligible for participation in the study:
• Subjects receiving any other investigational agents or anti-cancer therapy.
• Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
• History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
• Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women or nursing women
• Subjects with known HIV infection
• Known bleeding disorder or coagulopathy
• Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
• Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
• New York Heart Association Classification II, III, or IV (See Appendix D)
• Subjects with a blood pressure of \>140/90 mmHg. The BP should be taken using the method described in Section 9.3. Subjects taking antihypertensive medications must be taking ≤ 2 medications to obtain this level of BP control.
• Subjects with metastases that are currently involving the lumen of the gastrointestinal tract
• Subjects with squamous cell carcinoma of the lung
• Subjects with recent (within the last 8 weeks) hemoptysis \>2.5 mL and subjects with serious bleeding from another site within this timeframe

Sponsors & Collaborators

• OncoMed Pharmaceuticals, Inc.: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (7)

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, 5037, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Auckland Hospital

Grafton, Auckland, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

START Madrid

Madrid, Spain

Location

Related Publications (1)

• McKeage MJ, Kotasek D, Markman B, Hidalgo M, Millward MJ, Jameson MB, Harris DL, Stagg RJ, Kapoun AM, Xu L, Hughes BGM. Phase IB Trial of the Anti-Cancer Stem Cell DLL4-Binding Agent Demcizumab with Pemetrexed and Carboplatin as First-Line Treatment of Metastatic Non-Squamous NSCLC. Target Oncol. 2018 Feb;13(1):89-98. doi: 10.1007/s11523-017-0543-0.

  PMID: 29188408 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Neoplasm Metastasis

Interventions

demcizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 27, 2010
• Study Start: September 1, 2010
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

NZ (2); ES (1); AU (4)