Trebananib (AMG 386) in Combination With Docetaxel for Advanced Urothelial Carcinoma

NCT01907308 | Withdrawn Phase 2 DMC

• 2 other identifiers: 13-1502.ccNCI-2013-01348
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study plans to learn more about the combination of AMG 386 and docetaxel for the treatment of advanced urothelial cancer. Subjects are being asked to be in this research study because they have advanced urothelial cancer which has progressed after treatment with a platinum-based therapy. The hypothesis is that AMG 386 will increase the historical response rate of docetaxel as a single agent.

Conditions

Urothelial Carcinoma

Keywords

Bladder cancer; Urothelial cancer; Urothelial carcinoma

Outcome Measures

Primary Outcomes (1)

• Response rate

  Determine the objective response rate (by RECIST 1.1 criteria) for the combination of AMG 386 (Trebananib) with docetaxel for the treatment of advanced or metastatic urothelial carcinoma, after failure of a platinum-containing regimen

  Up to 21 days

Secondary Outcomes (1)

• Overall survival

  Up to 24 months

Study Arms (1)

Combination of AMG 386 with Docetaxel

EXPERIMENTAL

All treated patients will receive AMG 386 30mg/kg IV weekly plus docetaxel 75mg/m2 IV every 3 weeks.

Drug: AMG 386; Drug: Docetaxel

Interventions

AMG 386 DRUG

Patients will receive AMG 386 30mg/kg IV weekly plus docetaxel 75mg/m2 IV every 3 weeks.

Also known as: Trebananib

Combination of AMG 386 with Docetaxel

Docetaxel DRUG

Patients will receive AMG 386 30mg/kg IV weekly plus docetaxel 75mg/m2 IV every 3 weeks.

Also known as: Docefrez, Taxotere

Combination of AMG 386 with Docetaxel

Eligibility Criteria

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

You may qualify if:

• Subjects must have a histologically confirmed urothelial carcinoma. At least 50% of the tumor must demonstrate transitional cell histology.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• CT or MRI of the chest, abdomen, and pelvis, with or without contrast, within 28 days of registration. A whole body bone scan may be performed at the discretion of the treating physician.
• Only if clinically indicated, a CT or MRI (MRI preferred) scan of the brain within 28 days of registration.
• Progressive disease after a platinum-containing regimen (cisplatin or carboplatin) or intolerance to platinum-based therapy for urothelial carcinoma. Subjects who received adjuvant cisplatin or carboplatin-based chemotherapy for urothelial carcinoma and currently have recurrent or progressive disease are eligible.
• Men or women \> 18 years old
• Generally well-controlled blood pressure with systolic blood pressure ≤ 140 mmHg AND diastolic blood pressure ≤ 90 mmHg prior to enrolment or randomization. The use of anti-hypertensive medications to control hypertension is permitted
• Adequate organ and hematological function as evidenced by the following laboratory studies:
• a. Hematological function, as follows: i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelet count ≥ 100 x 109/L iii. Hemoglobin ≥= 9 g/dL b. Hepatic function, as follows: i. Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN), ii. Alanine aminotransferase (ALT) ≤ 2.5 x ULN iii. Alkaline phosphatase ≤ 2.0 x ULN iv. Total bilirubin within normal limits (WNL) c. Hemostatic function, as follows: i. International normalized ratio (INR) ≤ 1.5 ii. Activated Partial thromboplastin time (aPTT) ≤ 1.5 x ULN d. Renal function, as follows: i. Calculated creatinine clearance ≥ 40 cc/min according to the Cockcroft-Gault formula: Creatinine Clearance calculator (CrCl) (mL/min) = (140-age) x actual body weight (kg) (x 0.85 for females) 72 x serum creatinine (mg/dL) ii. Urinary protein quantitative value of ≤ 30 mg in urinalysis or ≤ 1+ on dipstick, unless quantitative protein is ≤ 1000 mg in a 24 hour urine sample e. Cardiac function, as follows (only in those with a known history of cardiac dysfunction or in those with symptoms indicative or cardiac dysfunction): i. Normal sinus rhythm or clinically stable arrhythmia well controlled on outpatient medication.
• ii. Left ventricular ejection fraction ≥ lower limit of normal (LLN) per institutional laboratory range, as determined by echocardiogram or multi gated acquisition scan (MUGA) scan within 28 days prior to enrollment. If no clear institutional standard, then the ejection fraction must be ≥ 50%.
• All baseline laboratory results must be from within 14 days of registration
• Competent to comprehend, sign, and date an institutional review board (IRB) - approved informed consent form
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Subject plans to begin protocol-directed therapy within 7 days of registration
• All patients will be offered enrollment in the correlative biomarkers study

You may not qualify if:

• Three or more previous systemic therapies or combination regimens for urothelial carcinoma (e.g. cisplatin given with gemcitabine is considered one regimen) in the recurrent or metastatic setting.
• Grade 2 or greater neuropathy
• Known history of central nervous system metastases. An MRI or CT scan of the brain will be performed within 28 days of study enrollment.
• History of arterial or venous thrombosis, including transient ischemic attack (TIA), within 12 months prior to enrollment
• History of clinically significant bleeding within 6 months of study enrollment
• Anticoagulation is allowed as long as the initiating thrombotic event was at least 12 months before enrollment. The use of aspirin and anti-platelet agents are also acceptable for any duration prior to enrollment. The concurrent use of low molecular weight heparin, heparinoids, or low dose warfarin (ie, 1 mg daily) for prophylaxis against thrombosis is acceptable while on study.
• Subjects with pleural effusions or ascites.
• Focal radiation therapy for palliation of pain from bony metastases within 21 days of study enrollment. Subjects who received radiation therapy must have recovered from all radiation induced toxicities prior to study enrollment
• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor including but not limited to, AZD-5180, XL-820, CEP 11981/SSR-106462, BSF-466,895, CGI-1842, LOC-590, XL-184, or CP- 8681596. (Previous treatment with bevacizumab is permitted.)
• Current or previous treatment with docetaxel. (Previous treatment with paclitaxel is permitted.)
• Treatment within 30 days prior to enrollment with strong immune modulators including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide.
• Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication
• Major surgery within 28 days before study enrollment or still recovering from prior surgery
• Minor surgical procedures, except placement of tunneled central venous access device within 3 days prior to enrollment/randomization.
• Non-healing wound, ulcer (including gastrointestinal) or fracture

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Amgen: collaborator

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

trebananib; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Thomas Flaig, MD

  Univerity of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 24, 2013
• Study Start: February 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 29, 2014

Record last verified: 2014-04