A Trial of AMG 479, Everolimus (RAD001) and Panitumumab in Patients With Advanced Cancer (RAP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Duke University
Sponsor:
Collaborators:
Amgen
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Herbert Hurwitz, MD, Duke University
ClinicalTrials.gov Identifier:
NCT01061788
First received: February 2, 2010
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

This open-label, non-randomized, dose escalation phase I biomarker trial of the triplet regimen of AMG 479, everolimus, and panitumumab for subjects with refractory advanced solid tumors is designed to assess the safety and tolerability of this combination as well as preliminary efficacy.


Condition Intervention Phase
Advanced Solid Tumors, Non-small Cell Lung Cancer
Drug: AMG 479, Everolimus, Panitumumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of the IGF-1R Antibody AMG 479 in Combination With Everolimus (RAD001) and Panitumumab in Patients With Advanced Cancer (The RAP Trial)

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • To define the maximal tolerated dose (MTD) and/or recommended phase II dose (RPTD) for the doublet AMG 479 in combination with everolimus in subjects with advanced solid tumors. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • To define the maximal tolerated dose (MTD) and/or recommended phase II dose (RPTD) for the triplet AMG 479 in combination with everolimus and panitumumab in subjects with advanced solid tumors. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To describe the toxicity profile seen with these combinations. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • To describe any signs of clinical activity, including response rate and progression free survival associated with these regimens. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: April 2010
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus, AMG 479, Panitumumab

Dose Escalation Cohort #, Subjects, Everolimus, AMG 479

  1. 3-6 subjects, Study drug administered per dose level
  2. 3-6 subjects, Study drug administered per dose level

    Expanded Cohort Subjects, Everolimus, AMG 479 20 subjects, study drug administered per dose level

    Dose Escalation, Cohort #, Subjects, Everolimus, AMG 479, Panitumumab

  3. 3-6 subjects, Study drug administered per dose level
  4. 3-6 subjects, Study drug administered per dose level

Expanded Cohort Subjects, Everolimus, AMG 479, Panitumumab 20 subjects, Study drug administered per dose level

NSCLC Cohort Subjects, Everolimus, AMG 479, 20 subjects, Study drug administered per dose level

Drug: AMG 479, Everolimus, Panitumumab

Dose Escalation Cohort #, Subjects, Everolimus, AMG 479

  1. 3-6 subjects, Study drug administered per dose level
  2. 3-6 subjects, Study drug administered per dose level

    Expanded Cohort Subjects, Everolimus, AMG 479 20 subjects, study drug administered per dose level

    Dose Escalation, Cohort #, Subjects, Everolimus, AMG 479, Panitumumab

  3. 3-6 subjects, Study drug administered per dose level
  4. 3-6 subjects, Study drug administered per dose level

Expanded Cohort Subjects, Everolimus, AMG 479, Panitumumab 20 subjects, Study drug administered per dose level

NSCLS Cohort Subjects, Everolimus, AMG 479, 20 subjects, Study drug administered per dose level


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically and/or cytologically confirmed malignant solid tumor that is refractory to standard therapies, or for which no standard therapies exist. Disease must be measurable by RECIST criteria.

    For the NSCLC expanded cohort only: Only histologically proven adenocarcinoma that is refractory to standard therapies.

  2. Age >18 years.
  3. ECOG performance status 0-2.
  4. Life expectancy of at least 3 months.
  5. Subjects must have adequate organ and marrow function as defined below:

    • Absolute neutrophil count >/=1,500/μl
    • Platelets >/=100,000/μl
    • Magnesium > 1.8 mg/dL
    • Phosphorus > 2.3 mg/dL
    • Total bilirubin </= 1.5 X upper limit of normal (ULN)
    • AST(SGOT)/ALT(SGPT) </=2.5 X ULN, </=5 X ULN if known hepatic metastases PT/INR; PTT </= 1.3; <1.3 X ULN
    • Creatinine clearance >/=40 mL/min/m2 by Cockroft-Gault or MDRD equation
    • Hemoglobin >9 g/dL
    • Continuation of erythropoietin products is permitted. Hemoglobin must be stable above 9 g/dL for at least 2 weeks without blood transfusion to maintain hemoglobin level.
    • Fasting blood sugar </= 160 mg/dL
    • Patient may be on diabetic medication to achieve glucose control:

      • Documented fasting blood sugars </= 160 mg/dL
      • Diabetic subjects who have recently had their glycemic control regimens adjusted and have documented fasting blood glucose concentrations ≤ 160 mg/dL may be considered regardless of HgbA1c value, if per investigator discretion the subject is considered to have adequate glycemic function
  6. Ability to understand and the willingness to sign a written informed consent document.
  7. NSCLS expanded cohort only: Total of 20 never smokers and non-smokers. Never smokers are defined as individuals who have never smoked and non-smokers are defined as individuals with a ≤5 pack year history (one pack daily for 5 years or equivalent).

Exclusion Criteria:

  1. Radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to day 1 of study drug.
  2. Active CNS metastases. MRI (or CT) required within 3 months of starting treatment for all tumor types known to commonly metastasize to the brain (i.e. all tumors except pancreas, colorectal, ovarian) and for all patients with CNS symptoms that may represent CNS metastases. Metastases which have been treated with radiotherapy > 2 months prior to start of protocol therapy and are asymptomatic (off steroid therapy for at least 1 month) may be included. Patients must have had normal or stable (if treated, no new lesions) brain imaging (CT or MRI) within the two months prior to day 1 of study drug.
  3. Inadequately controlled hypertension (defined as systolic blood pressure 140 and/or diastolic blood pressure > 90 mmHg). Initiation of antihypertensive is permitted provided adequate control is documented over at least 1 week prior to day 1 of study drug.
  4. Evidence of active bleeding diathesis or coagulopathy.
  5. No warfarin therapy. Low molecular weight heparin anticoagulation is permitted provided that patients have been clinically stable on anti-coagulation for at least 2 weeks prior to day 1 of study drug and meet platelet inclusion criteria. No history of active GI bleeding or other major bleeding within previous 6 months prior to day 1 of study drug.
  6. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of study drug (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study.
  7. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of study drug.
  8. Serious, non-healing wound, ulcer, or bone fracture.
  9. Any prior history of hypertensive crisis or hypertensive encephalopathy.
  10. New York Heart Association (NYHA) Grade II or greater congestive heart failure.
  11. History of clinically significant vascular disease, including any of the following within 6 months prior to day 1 of study drug: myocardial infarction or unstable angina, percutaneous coronary intervention, bypass grafting, ventricular arrhythmia requiring medication, stroke or transient ischemic attack, symptomatic peripheral arterial disease and/or involvement of great vessels by tumor with or without vascular grafting.
  12. Chronic treatment with systemic steroids or another immunosuppressive agent with the following exceptions:

    Intermittent steroids may be used on an as-needed basis (e.g. treatment for chemotherapy-related nausea.) Patients on physiologic replacement doses of steroids due to adrenal insufficiency for any reason may remain on these medications.

  13. A known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
  14. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g. inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection).
  15. Patient unwilling to or unable to comply with the protocol.
  16. Medical need for the continuous administration of any drugs which affect CYP3A4 though the use of low dose glucocorticoids (e.g. Dexamethasone </= 4 mg daily or equivalent) for anorexia and /or nausea is permitted.
  17. History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis, or any evidence of interstitial lung disease on baseline chest CT scan.
  18. Patients who are pregnant and/or lactating are excluded from this study. (The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be embryo- and feto-toxic. Women of child-bearing potential and men must agree to use two forms of adequate contraception (hormonal or barrier method of birth control; abstinence) prior to day 1 of study drug, the duration of study participation and 6 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician and study PI immediately. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. )
  19. Other concurrent severe and/or uncontrolled medical, psychiatric or social conditions that could compromise the safety or compliance of treatment as so judged by treating physician. Examples include but are not limited to:

    History of severely impaired lung function defined as spirometry and DLCO that is </= 50% of the normal predicted value and/or 02 saturation that is </= 88% at rest on room air.

    Uncontrolled diabetes mellitus consistent fasting blood glucose readings > 160 mg/dL or < 50 mg/dL). Use of diabetic medications is permitted.

    Hyperlipidemia (>CTC Grade 2: Total Cholesterol > 300-400; Triglycerides > 2.5 ULN). Use of lipid lowering agents is permitted.

    Other: e.g. severe infection, severe malnutrition, ventricular arrhythmias, known active vasculitis of any cause, tumor invasion of any major blood vessel, severe chronic liver or renal disease, active upper GI tract ulceration.

  20. No immunizations with attenuated live vaccines within one week of study entry or during study period.

21 Proteinuria at screening as demonstrated by either urine protein: creatinine (UPC) ratio greater than or equal to 1.0 or 24hr collection greater than 1g/24hr at screening.

22 NSCLC cohort only: Current smoker

  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: NCT01061788

Contacts
Contact: Tony Amara, MSW (919) 668-1861 anthony.amara@duke.edu
Contact: Brant Hamel, Ph.D (919) 668-1861 brant.hamel@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Tony Amara, MSW    919-668-1861    anthony.amara@duke.edu   
Contact: Brant Hamel, Ph.D    (919) 668-1861    brant.hamel@duke.edu   
Principal Investigator: Herbert Hurwiztz, MD         
Sponsors and Collaborators
Duke University
Amgen
Novartis Pharmaceuticals
Investigators
Principal Investigator: Herbert Hurwitz, MD Duke University
  More Information

No publications provided

Responsible Party: Herbert Hurwitz, MD, Assistant Professor of Medicine, Duke University
ClinicalTrials.gov Identifier: NCT01061788     History of Changes
Other Study ID Numbers: Pro00021317
Study First Received: February 2, 2010
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
Phase I
Solid Tumor
AMG 479
Panitumumab
Everolimus
RAD001
Duke
Subjects with refractory advanced solid tumors
non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Everolimus
Sirolimus
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 20, 2014