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


Phase 1
18 Years
N/A
Not Enrolling
Both
Histologically or Cytologically Documented Solid Tumors

Thank you

Trial Information

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


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

incidence of dose-limiting toxicities

Outcome 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

Safety Issue:

Yes

Principal Investigator

MD

Investigator Role:

Study Director

Investigator Affiliation:

Amgen

Authority:

Australia: Austin Health Human Research Ethics Committee

Study ID:

20050107

NCT ID:

NCT01235416

Start Date:

September 2005

Completion Date:

February 2010

Related Keywords:

  • Histologically or Cytologically Documented Solid Tumors
  • Neoplasms

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