A Pharmacokinetic Study of AMG 386 in Cancer Subjects With Normal and Impaired Renal Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01331941
First received: March 24, 2011
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

This is a phase 1, open-label pharmacokinetic study where up to 40 subjects with advanced solid tumors (up to 6-10 with normal renal function and up to 18-30 with varying degrees of renal dysfunction) will receive weekly doses of AMG 386 intravenously. The primary objective is to evaluate the pharmacokinetics (PK) of single agent AMG 386 in subjects with various degrees of renal function. Once the AMG 386 PK characterization is complete in the first 5 weeks of the study, all subjects will be allowed to continue to receive AMG 386 weekly only or subjects in group 1, 2 or 3 can opt to receive AMG 386 weekly in combination with paclitaxel until disease progression, unacceptable toxicity or withdrawal of consent.


Condition Intervention Phase
Advanced Solid Tumors
Kidney Disease
Renal Impairment
Drug: AMG 386 + Paclitaxel
Drug: AMG 386
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Pharmacokinetic Study of AMG 386 in Advanced Cancer Subjects With Normal and Impaired Renal Function

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Area under the serum concentration-time curve (AUC) [ Time Frame: Week 1-5. ] [ Designated as safety issue: No ]
  • Maximum observed concentration (Cmax) [ Time Frame: Week 1-5. ] [ Designated as safety issue: No ]
  • Time to maximum concentration (tmax) [ Time Frame: Week 1-5. ] [ Designated as safety issue: No ]
  • Minimum observed concentration (Cmin) [ Time Frame: Week 1-5. ] [ Designated as safety issue: No ]
  • Clearance (CL) of AMG 386 calculated as dose divided by AUC on week 5. [ Time Frame: Week 1-5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events as a measure of safety [ Time Frame: Weekly at each visit AMG 386 is administered, on day 30, 31 and 32 when only PK assessments are scheduled up to and including the last study visit 30 days after the last AMG 386 administration. ] [ Designated as safety issue: Yes ]
  • Changes in vital signs as a measure of safety [ Time Frame: Weekly at each visit AMG 386 is administered up to and including the last study visit 30 days after the last AMG 386 administration. ] [ Designated as safety issue: Yes ]
  • Changes in clinical laboratory tests as a measure of safety [ Time Frame: Weekly from week 1-9 then every 4 weeks thereafter including the last study visit 30 days after the last AMG 386 administration. ] [ Designated as safety issue: Yes ]
  • Anti-AMG 386 antibody formation [ Time Frame: Week 1, week 5, week 9 and every 16 weeks thereafter including the last study visit 30 days after the last AMG 386 administration. ] [ Designated as safety issue: Yes ]
  • Tumor objective response measured by CT or MRI (without Gadolinium contrast agents) and assessed by RECIST 1.1 criteria. [ Time Frame: Week 5 and every 8 weeks thereafter until the subject's end of participation in the study. ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: September 2011
Study Completion Date: November 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Cancer subjects with normal renal function.
Drug: AMG 386 + Paclitaxel
15 mg/kg IV (in the vein) of AMG 386 weekly + 80 mg/m^2 IV (in the vein) 3 weeks on/1 week off, optional beginning week 6 until progression, unacceptable toxicity, or withdrawal of consent.
Drug: AMG 386
15 mg/kg IV (in the vein) weekly beginning week 1 day 1 until progression, unacceptable toxicity, or withdrawal of consent.
Experimental: Group 3
Cancer subjects with moderate renal impairment.
Drug: AMG 386 + Paclitaxel
15 mg/kg IV (in the vein) of AMG 386 weekly + 80 mg/m^2 IV (in the vein) 3 weeks on/1 week off, optional beginning week 6 until progression, unacceptable toxicity, or withdrawal of consent.
Drug: AMG 386
15 mg/kg IV (in the vein) weekly beginning week 1 day 1 until progression, unacceptable toxicity, or withdrawal of consent.
Experimental: Group 4
Cancer subjects with severe renal impairment.
Drug: AMG 386
15 mg/kg IV (in the vein) weekly beginning week 1 day 1 until progression, unacceptable toxicity, or withdrawal of consent.
Experimental: Group 2
Cancer subjects with mild renal impairment.
Drug: AMG 386 + Paclitaxel
15 mg/kg IV (in the vein) of AMG 386 weekly + 80 mg/m^2 IV (in the vein) 3 weeks on/1 week off, optional beginning week 6 until progression, unacceptable toxicity, or withdrawal of consent.
Drug: AMG 386
15 mg/kg IV (in the vein) weekly beginning week 1 day 1 until progression, unacceptable toxicity, or withdrawal of consent.

  Eligibility

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

Inclusion Criteria:

  • Men or women ≥ 18 years of age
  • Must have a pathologically documented, and definitively diagnosed, advanced solid tumor that is refractory to standard treatment, or for which no curative therapy is available, or for subjects who refuse standard therapy
  • Evaluable OR measurable disease by RECIST 1.1 criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Life expectancy of > 3 months, in the opinion of and as documented by the investigator
  • Subject or subject's legally acceptable representative has provided informed consent

Exclusion Criteria:

  • Subjects with gastric cancer or any malignancy with purely squamous cell histology
  • Known history of primary central nervous system (CNS) tumors or CNS metastases
  • Myocardial infarction within 1 year before study day 1, unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association > class II, uncontrolled hypertension [diastolic > 90 mmHg; systolic > 150 mmHg in repeated measurements])
  • History of stroke, arterial or venous thrombosis, or pulmonary embolism within 1 year before study day 1
  • Active grade 2 or greater peripheral vascular disease or peripheral edema
  • History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis)
  • Non-healing wound, ulcer (including gastrointestinal) or fracture
  • Known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection
  • Major surgery within 4 weeks before study day 1
  • Absolute neutrophils count (ANC) < 1.0 x 10^9/L; or platelet count < 100 x 10^9/L; or hemoglobin < 9 g/dL; or PTT / aPTT > 1.5 x institutional upper limit of normal (ULN) ); or INR > 1.5
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN (> 5.0 x ULN if liver metastases present)
  • Alkaline phosphatase > 2.5 x ULN (> 5.0 x ULN if attributable to liver or bone metastasis)
  • Total bilirubin > 1.5 x ULN
  • Other investigational procedures during the study
  • Previous anti-cancer therapy or investigational agent within 4 weeks prior to study day 1
  • Anticoagulation therapy within 4 weeks of study day 1 and while on study (except low dose warfarin (≤ 2 mg/kg) for prophylaxis against central venous catheter thrombosis)
  • Men and women of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and an additional 6 months after the last dose of AMG 386. Highly effective methods of birth control include sexual abstinence (men, women); vasectomy or a condom with spermicide (men) in combination with barrier methods, hormonal birth control or IUD (women).
  • Women who are lactating/breastfeeding.
  • Women with a positive pregnancy test.
  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: NCT01331941

Locations
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30332
United States, Illinois
Research Site
Chicago, Illinois, United States, 60637
United States, New Hampshire
Research Site
Lebanon, New Hampshire, United States, 03756
United States, Ohio
Research Site
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01331941     History of Changes
Other Study ID Numbers: 20090277
Study First Received: March 24, 2011
Last Updated: February 6, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
AMG 386
Pharmacokinetic
Renal Impairment

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency
Urologic Diseases
Paclitaxel
Trenananib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014