AMG 706 and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2007 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00324597
First received: May 10, 2006
Last updated: September 16, 2013
Last verified: April 2007
  Purpose

RATIONALE: AMG 706 may stop the growth of cancer cells by blocking blood flow to the cancer or by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving AMG 706 together with gemcitabine may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of AMG 706 when given together with gemcitabine in treating patients with advanced solid tumors or lymphoma.


Condition Intervention Phase
Lung Cancer
Lymphoma
Lymphoproliferative Disorder
Unspecified Adult Solid Tumor, Protocol Specific
Drug: gemcitabine hydrochloride
Drug: motesanib diphosphate
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-Label, Sequential, Dose-Finding, Study of AMG 706 in Combination With Gemcitabine to Treat Subjects With Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of dose-limiting toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Maximum tolerated dose as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic profiles as measured by blood sampling at weeks 1, 2, 9, 13, 21, 29, 37, 45, and 49 [ Designated as safety issue: No ]
  • Incidence of adverse events, serious adverse events, and laboratory abnormalities not defined as dose-limiting toxicities as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Response rate (complete and partial response) as measured by modified RECIST at weeks 12, 24, 36, 48, and 49 [ Designated as safety issue: No ]
  • Biomarkers as measured by RNA transcript profiling and/or proteomic methods at weeks 1, 2, 4, 9, 13, 21, 29, 37, 45, 49 [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: October 2005
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose and safety of AMG 706 when given in combination with gemcitabine hydrochloride in patients with advanced solid tumors or lymphoma.

Secondary

  • Determine the pharmacokinetic profiles of this regimen in these patients.

OUTLINE: This is a multicenter, open-label, dose-escalation study of AMG 706.

Patients receive oral AMG 706 once daily on days 2-56 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 of course 1. For all subsequent courses, patients receive oral AMG 706 on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AMG 706 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.

During the first course of study treatment, patients undergo blood collection periodically for pharmacokinetic analysis.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: Approximately 18 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed advanced solid tumors or lymphoma
  • Must have measurable disease outside a previously irradiated field OR regrowth of tumor within a previously irradiated field
  • Must be a candidate for gemcitabine hydrochloride treatment, in the opinion of the investigator
  • No untreated or symptomatic brain metastases
  • No tumors with direct bowel invasion
  • No other hematological malignancies
  • No non-small cell lung cancer of squamous cell histology or large central tumor (lesions ≥ 3 cm and located adjacent to or within the hilum or mediastinum)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Not pregnant
  • No nursing during and for 6 months after completion of study treatment
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • Negative pregnancy test
  • Able to swallow oral medication
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min
  • Albumin-adjusted calcium ≥ 8 mg/dL
  • Urine protein < 30 mg/dL by urinalysis or < 1+ by dipstick OR < 500 mg by 24-hour urine collection
  • AST or ALT ≤ 2.5 times upper limit of normal (ULN) (5.0 times ULN in the presence of liver metastasis or primary hepatic neoplasm)
  • Bilirubin ≤ 2 times ULN
  • PT ≤ 2.0
  • INR or PTT ≤ 1.5 times ULN
  • Systolic blood pressure (BP) ≤ 145 mm Hg and diastolic BP ≤ 85 mm Hg (stable antihypertensive medication allowed)
  • No myocardial infraction within the past year
  • No arterial thrombosis or deep vein thrombosis within the past year
  • No unstable angina
  • No congestive heart failure
  • No New York Heart Association class III-IV cardiac disease
  • No other unstable or uncontrolled disease or condition relating to or impacting cardiac function
  • No HIV positivity
  • No other condition that would preclude study participation, compliance, or follow-up assessments

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior enrollment into this study
  • At least 1 month since prior investigational device or drug trial
  • At least 1 month since prior major surgical procedure
  • At least 3 weeks since prior systemic chemotherapy
  • At least 2 weeks since prior radiotherapy
  • At least 2 weeks since prior rifampin or phenobarbital
  • At least 1 week since prior treatment with any of the following:

    • Ketoconazole
    • Itraconazole
    • Clarithromycin
    • Erythromycin
    • Cyclosporine or tacrolimus
    • Nefazodone
    • Herbal medications containing Hypericum perforatum (St. John's wort)
  • At least 1 week since prior and no concurrent warfarin

    • Concurrent prophylactic anticoagulation therapy (e.g., low-dose warfarin [≤ 2 mg/day] or low molecular weight heparin) for venous or arterial access devices allowed
  • No prior or concurrent kinase insert domain-receptor inhibitors
  • No concurrent chemotherapy, radiotherapy, hormone-directed cancer therapy, or tumor-directed antibody therapy

    • Gonadotropin releasing-hormone agonist therapy allowed
  • No concurrent interferon
  • No concurrent grapefruit juice or whole grapefruit
  • No other concurrent standard or investigational drugs or antitumor treatment, including c-kit, platelet-derived growth factor, vascular endothelial growth factor, or epidermal growth factor inhibitors
  • No elective surgery during or for 2 weeks after completion of the last dose of AMG 706
  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: NCT00324597

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Carolyn Britten, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00324597     History of Changes
Other Study ID Numbers: CDR0000481095, UCLA-0506055-01
Study First Received: May 10, 2006
Last Updated: September 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
recurrent adult grade III lymphomatoid granulomatosis
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
stage III small lymphocytic lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
stage III adult T-cell leukemia/lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
splenic marginal zone lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lung Neoplasms
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma, Large-Cell, Immunoblastic
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Niacinamide
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

ClinicalTrials.gov processed this record on August 28, 2014