A Phase 1b, Open-label, Dose-finding Study of AMG 706 in Combination With Gemcitabine and Erlotinib to Treat Subjects With Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
Amgen
ClinicalTrials.gov Identifier:
NCT01235416
First received: October 29, 2010
Last updated: January 20, 2011
Last verified: January 2011
  Purpose

This study is an open-label, dose-finding study to determine the target or maximum-tolerated dose and to characterize the safety and pharmacokinetic profile of AMG 706 administered in combination with erlotinib with or without gemcitabine in subjects with solid tumors.


Condition Intervention Phase
Histologically or Cytologically Documented Solid Tumors
Drug: AMG 706
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 1b, Open-label, Dose-finding Study of AMG 706 in Combination With Gemcitabine and Erlotinib to Treat Subjects With Solid Tumors

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • incidence of dose-limiting toxicities [ Time Frame: Subjects will be in this study for up to 54 weeks (ie, 2 weeks screening, 48 weeks treatment and 4 weeks follow-up) or longer if subjects are deemed to have continuous clinical benefit from the combination chemotherapy and AMG 706 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of adverse events (including serious and treatment-related) and significant laboratory values other than those defined as dose-limiting toxicities [ Time Frame: Subjects will be in this study for up to 54 weeks (ie, 2 weeks screening, 48 weeks treatment and 4 weeks follow-up) or longer if subjects are deemed to have continuous clinical benefit from the combination chemotherapy and AMG 706 ] [ Designated as safety issue: Yes ]
  • pharmacokinetic profiles of erlotinib and AMG 706 [ Time Frame: Subjects will be in this study for up to 54 weeks (ie, 2 weeks screening, 48 weeks treatment and 4 weeks follow-up) or longer if subjects are deemed to have continuous clinical benefit from the combination chemotherapy and AMG 706 ] [ Designated as safety issue: Yes ]

Enrollment: 57
Study Start Date: September 2005
Study Completion Date: February 2010
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AMG 706 50mg
50 mg, once daily. (Cohort 1)
Drug: AMG 706
In each of these 3 planned treatment cohorts, approximately 6 evaluable subjects will be treated with gemcitabine (1000-mg/m2 intravenously over 30 minutes, once weekly starting on day 1, week 1 of cycle 1) and erlotinib (100 mg orally once daily starting on day 1, week 1 of cycle 1)
Active Comparator: AMG 706 75mg
75 mg, twice daily. (Cohort 2)
Drug: AMG 706
In each of these 3 planned treatment cohorts, approximately 6 evaluable subjects will be treated with gemcitabine (1000-mg/m2 intravenously over 30 minutes, once weekly starting on day 1, week 1 of cycle 1) and erlotinib (100 mg orally once daily starting on day 1, week 1 of cycle 1)
Active Comparator: AMG 706 125mg
125 mg, once daily. (Cohort 3)
Drug: AMG 706
In each of these 3 planned treatment cohorts, approximately 6 evaluable subjects will be treated with gemcitabine (1000-mg/m2 intravenously over 30 minutes, once weekly starting on day 1, week 1 of cycle 1) and erlotinib (100 mg orally once daily starting on day 1, week 1 of cycle 1)

  Eligibility

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

Inclusion Criteria:

  • histologically or cytologically documented solid tumors
  • candidates for gemcitabine and erlotinib treatment (for cohorts with gemcitabine), in the opinion of the investigator
  • candidates for erlotinib treatment (for cohorts without gemcitabine), in the opinion of the investigator
  • Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2 (see Appendix E)
  • systolic blood pressure ≤ 145 mm Hg and diastolic blood pressure ≤ 85 mm Hg (hypertension therapy is allowed)
  • at least 18 years of age when written informed consent is obtained
  • before any study-specific procedure is performed, the appropriate approved written informed consent must be obtained (Section 12.1).

Exclusion Criteria:

  • nonsmall-cell lung cancer with squamous-cell histology
  • large central tumor lesions (ie, ≥ 3 centimeters and located adjacent to or within the hilum or mediastinum)
  • direct bowel wall invasion except for primary tumors of the bowel
  • evidence of active bleeding or bleeding diathesis
  • total gastrectomy
  • hematologic malignancies
  • untreated or symptomatic brain metastases
  • history or evidence of interstitial lung disease
  • past or current history of second neoplasm, except for curatively treated non-melanoma skin cancer, carcinoma in situ of the cervix and other primary solid cancer with no known active disease present and no curative treatment administered for the last 3 years
  • documented myocardial infarction within 1 year before study day 1
  • arterial thrombosis or deep vein thrombosis within 1 year before study day 1
  • unstable or uncontrolled disease/condition related to or impacting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association (NYHA) > class II [Appendix F])
  • major surgical procedure within 30 days before study day 1
  • known positive test for human immunodeficiency virus (HIV)
  • absolute neutrophil count (ANC) < 1.5 x 109 /L
  • platelet count < 100 x 109 /L or > 850 x 109 /L
  • hemoglobin < 9 g/dL
  • serum creatinine > 2.0 mg/dL or calculated clearance < 40 mL/minute
  • albumin-adjusted serum calcium < 2.0 mmol/L (8.0 mg/dL)
  • urine protein quantitative value of ≥ 30 mg/dL in urinalysis or ≥ 1+ on dipstick, unless 24-hour urine protein is < 500 mg
  • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN) or AST or ALT > 5.0 x ULN if the subject has documented liver metastasis or primary hepatic neoplasm
  • total bilirubin > 2 x ULN (> 3 x ULN for subjects with Gilbert syndrome. Subjects with UGT1A1 promoter polymorphism, i.e. Gilbert syndrome, must be confirmed by genotyping or Invader® UGT1A1 Molecular Assay)
  • prothrombin time > 2.0 international normalized ratio or partial thromboplastin time > 1.5 X ULN
  • currently or previously treated with bevacizumab or small molecular inhibitors of VEGF including but not limited to SU11248 (sunitinib malate), PTK787 (vatalanib), AZD 2171, AEE-788, BAY 43- 9006 (sorafenib tosylate) and AMG 706, unless approved by Amgen
  • previously treated with erlotinib
  • previously treated with gemcitabine (for cohorts with gemcitabine) unless approved by Amgen
  • currently treated with interferon
  • systemic chemotherapy within 21 days before study day 1
  • radiation therapy within 14 days before study day 1
  • concurrent or prior treatment with rifampin, rifabutin, rifapentin, phenytoin, carbamazepine, or phenobarbital within 14 days before study day 1
  • treatment with strong CYP 3A inhibitors or inducers (such as but not limited to ketoconazole, itraconazole, clarithromycin, erythromycin or nefazodone) or immune modulators (such as but not limited to cyclosporine and tacrolimus) 7 days before study day 1
  • treatment with herbal medications containing St John's Wort within 7 days before study day 1
  • treatment for systemic infection within 14 days before study day 1
  • treated with > 1 mg/day of warfarin within 7 days before study day 1
  • any condition which in the investigator's opinion makes the subject unsuitable for study participation
  • not yet completed at least 30 days since ending other investigational device/drug trial(s), or subject is receiving other investigational treatments
  • pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding
  • not using adequate contraceptive precautions
  • unable to swallow oral medications
  • previously enrolled into this study
  • not available for follow-up assessments
  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: NCT01235416

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: Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier: NCT01235416     History of Changes
Other Study ID Numbers: 20050107
Study First Received: October 29, 2010
Last Updated: January 20, 2011
Health Authority: Australia: Austin Health Human Research Ethics Committee
Australia: Bellberry Human Research Ethics Committee
Australia: Central Northern Adelaide Health Service Ethics of Human Research Committee
Canada: University Health Network (UHN), Research Ethics Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 10, 2014