A Trial of AMG 479, Everolimus (RAD001) and Panitumumab in Patients With Advanced Cancer - QUILT-3.007

NCT01061788 | Completed Phase 1 DMC

• 1 other identifier: Pro00021317
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumors, Non-small Cell Lung Cancer

Keywords

Phase I; Solid Tumor; AMG 479; Panitumumab; Everolimus; RAD001; Duke; Subjects with refractory advanced solid tumors; non-small cell lung cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  3 years

• 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.

  3 years

Secondary Outcomes (2)

• To describe the toxicity profile seen with these combinations.

  3 years

• To describe any signs of clinical activity, including response rate and progression free survival associated with these regimens.

  3 years

Study Arms (1)

Everolimus, AMG 479, Panitumumab

EXPERIMENTAL

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

Interventions

AMG 479, Everolimus, Panitumumab DRUG

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

Everolimus, AMG 479, Panitumumab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age \>18 years.
• Karnofsky Performance Status of 60-100.
• Life expectancy of at least 3 months.
• 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

You may not qualify if:

• Radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to day 1 of study drug.
• For the NSCLC expanded cohort only: Palliative radiation therapy ≤14 days of day 1 of study drug.
• 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.
• For the NSCLC expanded cohort only: Radiation ≤ 14 days prior to day 1 of study drug. Subjects must be off steroids for \> 14 days prior to day 1 of study drug and anticonvulsants must be discontinued.
• 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.
• Evidence of active bleeding diathesis or coagulopathy. For the NSCLC expanded cohort only: History of "blood tinged" sputum allowed.
• 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.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of study drug.
• Serious, non-healing wound, ulcer, or bone fracture.
• Any prior history of hypertensive crisis or hypertensive encephalopathy.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• 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.
• 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.
• A known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.

Sponsors & Collaborators

• Jeffrey Clarke: lead
• NantCell, Inc.: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ganitumab; Everolimus; Panitumumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Herbert Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 2, 2010
• First Posted: February 3, 2010
• Study Start: April 1, 2010
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

US (1)