An A/B Dose Escalation Study of AbGn-7 Alone and With FOLFOX7 Treatment in Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbGenomics B.V Taiwan Branch
ClinicalTrials.gov Identifier:
NCT01466569
First received: November 2, 2011
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to determine the safety and tolerability profile including the dose limiting toxicity of AbGn-7 in patients with chemo-refractory advanced solid tumor of epithelial origin, and of AbGn-7 in combination with FOLFOX7 in patients with chemo-naive/chemo-refractory recurrent, locally advanced or metastatic gastric cancer.


Condition Intervention Phase
Solid Tumor of Epithelial Origin
Gastric Cancer
Drug: AbGn-7
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 A/B Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AbGn-7 Therapy Alone and in Combination With the FOLFOX7 Treatment Regimen in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by AbGenomics B.V Taiwan Branch:

Primary Outcome Measures:
  • Safety will be assessed by analysis of adverse event, clinical laboratory tests and physical examination [ Time Frame: 10 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics will be assessed at 3 different dose levels in phase 1a and at 2 dose levels in phase 1b [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Serum anti-drug antibodies will be assessed at 3 different dose levels in phase 1a and at 2 dose levels in phase 1b [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Tumor response rate by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: November 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AbGn-7 phase 1a cohort 1 Drug: AbGn-7
Phase 1a: dose escalation; Drug: AbGn-7 weekly iv infusion Duration: 6 weeks
Experimental: AbGn-7 phase 1a cohort 2 Drug: AbGn-7
Phase 1a: dose escalation; Drug: AbGn-7 weekly iv infusion Duration: 6 weeks
Experimental: AbGn-7 phase 1a cohort 3 Drug: AbGn-7
Phase 1a: dose escalation; Drug: AbGn-7 weekly iv infusion Duration: 6 weeks
Experimental: AbGn-7 phase 1b cohort 1 Drug: AbGn-7
Phase 1b: two doses (one dose below MTD/MAD and MTD/MAD as determined in phase 1a) Drug: AbGn-7 weekly iv infusion combined with FOLFOX7 Duration: 6 weeks
Experimental: AbGn-7 phase 1b cohort 2 Drug: AbGn-7
Phase 1b: two doses (one dose below MTD/MAD and MTD/MAD as determined in phase 1a) Drug: AbGn-7 weekly iv infusion combined with FOLFOX7 Duration: 6 weeks

Detailed Description:

Monoclonal antibodies, alone or in combination with chemotherapeutic agents, have been proven to be effective treatment for many malignant diseases in human. Antibodies can mediate cytotoxicity through complement dependent cytotoxicty (CDC), antibody dependent cell mediated cytotoxicity (ADCC) or apoptosis.

AbGn-7 was identified based on its direct killing (apoptosis-inducing) activities towards cancer cells expressing its epitope. In vitro data also demonstrated its ability to elicit CDC and ADCC. The in vivo xenograft study of AbGn-7 demonstrated that AbGn-7 alone or in combination with chemotherapeutic agents successfully suppressed the growth of gastric, pancreatic, and colorectal tumours. The NHP study proved the safety profile of AbGn-7. The present Phase 1 clinical study is designed to evaluate the safety and tolerability of AbGn-7 alone in patients with solid tumors of epithelial origin (Phase 1a) and in combination with a current chemotherapeutic regimen FOLFOX7 in patients with recurrent, locally advanced or metastatic gastric carcinoma (Phase 1b).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. must provide written informed consent.
  2. must be ≥18 years of age, either sex and of any race/ethnicity.
  3. Phase 1a: must have a histologically or cytologically confirmed advanced malignant solid tumor of epithelial origin and must have failed on previous chemotherapy. Phase 1b: must have a histologically or cytologically confirmed, recurrent, locally advanced or metastatic gastric cancer with measurable disease; must be chemo-naïve or must have failed on previous chemotherapy; must not have received an oxaliplatin-based chemotherapeutic regimen or monoclonal antibody therapy.
  4. must have an Eastern Cooperative Oncology Group Performance Status of ≤2.
  5. must have adequate hematological, renal and liver functions within 3 weeks prior to first study drug administration as evidenced by: a) Absolute neutrophil count ≥1.5 x 109/L, b) Hemoglobin ≥90 g/L (≥80 g/L for patients with documented renal cell carcinoma), c) Platelet count ≥100 x 109/L, d) Serum creatinine ≤1.5 x upper limit of normal ULN or a calculated creatinine clearance ≥60 mL/minute, e) Total bilirubin <1.5 x ULN, except for patients with documented Gilbert's disease, f) AST/SGOT and ALT/SGPT < 2.5 x ULN, or, in the presence of documented liver metastases, ≤5 x ULN.
  6. must be able to adhere to dose and visit schedules.
  7. Each female patient of childbearing potential must agree to use a medically accepted method of contraception or to abstain from sexual intercourse and each male patient must agree to use a medically accepted method of contraception or to abstain from sexual intercourse during the study and for 60 days after stopping the study drug.
  8. A life expectancy of at least 3 months.
  9. Available tumor tissue in the form of unstained slides for determination of AbGn-7 epitope expression (optional for Phase 1a, obligatory for Phase 1b). Patients without archival/banked tumor tissue obtained at the time of initial diagnosis must have a biopsy performed according to institutional guidelines prior to the initiation of treatment.

Exclusion Criteria:

  1. No current treated or untreated leptomeningeal metastasis or a metastatic CNS lesion.
  2. For Phase 1a, patients should not have received chemotherapy within 30 days prior to initiation of AbGn-7 therapy. For Phase 1b, patients should not have received oxaliplatin-based chemotherapy or monoclonal antibody therapy for their gastric cancer prior to enrollment.
  3. Have note received radiation therapy within 3 weeks prior to first study drug administration and must have adequately recovered from any associated toxicity and/or complications of this intervention.
  4. Have not undergone major surgery within 3 weeks prior to the first study drug administration and must have adequately recovered from the toxicity and/or complications of these interventions.
  5. No current human immunodeficiency virus (HIV) infection or a current HIV-related malignancy.
  6. No current active hepatitis B or C.
  7. No any serious or uncontrolled infection.
  8. No uncontrolled diabetes mellitus, defined as a HbA1c of ≥7.5% in a patient with documented diabetes mellitus.
  9. No any of the following within 6 months prior to first study drug administration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, clinically significant cardiac dysrhythmia or clinically significant ECG abnormality, cerebrovascular accident or transient ischemic attack, or seizure disorder.
  10. No persistent, unresolved NCI CTCAE Grade ≥2 drug-related toxicity associated with previous chemotherapy.
  11. Not participating in any other clinical study with a potentially therapeutic agent, or have not received another investigational product within 21 days.
  12. No any clinically significant condition or situation which would interfere with the study evaluations or optimal participation in the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01466569

Locations
United States, Pennsylvania
Fox Chase Cancer Center
Rockledge, Pennsylvania, United States, 19046
United States, Texas
The University of Texas Health Science Center-CTRC
San Antonio, Texas, United States, 78229
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 104
MacKay Memorial Hospital
Taipei, Taiwan, 104
Sponsors and Collaborators
AbGenomics B.V Taiwan Branch
Investigators
Study Director: Shih-Yao Lin, MD, PhD AbGenomics B.V Taiwan Branch
Principal Investigator: Devalingham Mahalingam, MD The University of Texas Health Science Center-CTRC
Principal Investigator: Anthony Olaszanski, MD, RPh Fox Chase Cancer Center
Principal Investigator: Kuen-Hui Yeh, MD National Taiwan University Hospital
Principal Investigator: Ruey-Kuen Hsieh, MD Mackay Memorial Hospital
  More Information

No publications provided

Responsible Party: AbGenomics B.V Taiwan Branch
ClinicalTrials.gov Identifier: NCT01466569     History of Changes
Other Study ID Numbers: AbGenomics-2010.007.01
Study First Received: November 2, 2011
Last Updated: November 20, 2013
Health Authority: United States: Food and Drug Administration
Taiwan : Food and Drug Administration

Keywords provided by AbGenomics B.V Taiwan Branch:
Advanced Solid Tumor
Gastric Cancer
Oncology
monoclonal Antibody

Additional relevant MeSH terms:
Stomach Neoplasms
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on April 14, 2014