Phase 2 Study of AMG 386 (20060439) in Combination With Cisplatin & Capecitabine in Subjects With Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00583674
First received: December 20, 2007
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

This is a phase 2, randomized, double blind, placebo controlled, multi-center study to estimate the improvement in progression free survival (compared to control subjects) and evaluate the safety and tolerability of AMG 386 in combination with Cisplatin & Capecitabine in the treatment of subjects with Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma. AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.


Condition Intervention Phase
Gastrointestinal Cancer
Drug: AMG 386 placebo
Drug: AMG 386 10mg/kg
Drug: AMG 386 3mg/kg
Drug: Cisplatin
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Multi-Center, Phase 2 Study to Estimate the Efficacy and Evaluate the Safety and Tolerability of Cisplatin & Capecitabine (CX) in Combination With AMG 386 or Placebo in Subjects With Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 22 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and Tolerability [ Time Frame: 22 months ] [ Designated as safety issue: Yes ]
  • Objective Response Rate (ORR) [ Time Frame: 22 months ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) [ Time Frame: 22 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: 22 months ] [ Designated as safety issue: No ]
  • Time to Progression (TTP) [ Time Frame: 22 months ] [ Designated as safety issue: No ]
  • Time to Response [ Time Frame: 22 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: 22 months ] [ Designated as safety issue: No ]
  • Patient Reported Outcomes [ Time Frame: 22 months ] [ Designated as safety issue: No ]

Enrollment: 171
Study Start Date: December 2007
Study Completion Date: June 2012
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B Drug: AMG 386 3mg/kg
AMG 386 3 mg/kg IV QW until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Drug: Cisplatin
Cisplatin 80 mg/m2 IV Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Drug: Capecitabine
Capecitabine 1000 mg/m2 PO BID x 14 days Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Experimental: A Drug: AMG 386 10mg/kg
AMG 386 10 mg/kg IV QW until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Drug: Cisplatin
Cisplatin 80 mg/m2 IV Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Drug: Capecitabine
Capecitabine 1000 mg/m2 PO BID x 14 days Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Active Comparator: C Drug: AMG 386 placebo
AMG 386 placebo IV QW until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Drug: Cisplatin
Cisplatin 80 mg/m2 IV Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death
Drug: Capecitabine
Capecitabine1000 mg/m2 PO BID x 14 days Q3W until radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death

  Eligibility

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

Inclusion Criteria:

  • Disease Related

    • Histologically or cytologically confirmed adenocarcinoma of the stomach, gastroesophageal junction or distal esophagus with metastatic disease
    • Measurable or non-measurable disease per RECIST Guidelines
    • Prior gastrectomy (total or partial) may be allowed as long as subjects can take oral medications and meet all other inclusion/exclusion criteria. Subjects may not take crushed or dissolved capecitabine via a feeding/gastrostomy tube
    • Palliative radiotherapy for metastatic esophageal or gastric cancer prior to study entry may be allowed as long as all toxicities from radiotherapy have resolved and the radiotherapy was not to the only site of known metastatic disease
  • Demographic

    •18 years of age or older at the time the written informed consent is obtained

  • General

    • Able to swallow oral medication
    • ECOG performance status of 0 or 1
  • Laboratory

    • Adequate organ and hematological function as evidenced by laboratory studies prior to randomization

Exclusion Criteria:

  • Disease Related

    • Prior chemotherapy for metastatic disease (1st line)
    • Less than 12 months have elapsed from completion of previous adjuvant or neoadjuvant chemotherapy or chemoradiotherapy
    • Subjects with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy
    • Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities
    • Current or prior history of central nervous system metastases
    • History of arterial or deep venous thromboembolism within 12 months prior to randomization
    • History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization
    • Major surgical procedure within 28 days prior to randomization
    • Minor surgical procedure, placement of central venous access device or fine needle aspiration within 3 days prior to randomization
    • Prior malignancy except: malignancy treated with curative intent and without evidence of active disease for ≥ 3 years prior to randomization and felt to be at low risk for recurrence by treating physician, adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease, adequately treated cervical carcinoma in situ without evidence of disease, prostatic intraepithelial neoplasia without evidence of prostate cancer
    • Prior malignancy (other than in situ cervical cancer, or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years prior to randomization
    • Clinically significant cardiovascular diseases within 12 months prior to randomization
    • Presence of clinically significant non-healing wound, ulcer (including gastrointestinal) or fracture as judged by the investigator
    • Ongoing or clinically significant active infection as judged by the investigator
    • Known hypersensitivity to bacterial proteins, or any of the drugs required in this study
    • Known peripheral neuropathy ≥Grade 1
    • Known dihydropyrimidine dehydrogenase deficiency
    • Known hypersensitivity to 5-FU/capecitabine
    • Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
    • Known active or chronic hepatitis
  • Medications

    • Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2
    • Treatment with immune modulators such as cyclosporine or tacrolimus within 30 days prior to randomization
    • Treatment with sorivudine or its chemically related analogues
    • Anticoagulants (other than aspirin and anti-platelet agents) within 7 days prior to randomization. The concurrent use of low molecular weight heparin or heparanoids or low dose warfarin (i.e, ≤ 1 mg daily) for prophylaxis against thrombosis is acceptable while on study
  • General

    • Not yet completed at least 30 days since ending other investigational device/drug trial(s), or subject is receiving other investigational treatments
    • Pregnant or is breast feeding
  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: NCT00583674

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00583674     History of Changes
Other Study ID Numbers: 20060439
Study First Received: December 20, 2007
Last Updated: April 21, 2014
Health Authority: Australia: Therapeutic Goods Administration
Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
Austria: Bundesamt für Sicherheit im Gesundheitswesen
Belgium: Directorate-General for Medicinal Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hungary: National Institute of Pharmacy
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
Gastric Cancer
Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma
AMG 386
Cisplatin
Capecitabine

Additional relevant MeSH terms:
Adenocarcinoma
Gastrointestinal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Capecitabine
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 22, 2014