Everolimus, Fluorouracil, Leucovorin, Panitumumab, and Oxaliplatin in Treating Patients With Tumors That Did Not Respond to Treatment

May 1, 2017 updated by: UNC Lineberger Comprehensive Cancer Center

A Sequential Phase I Study Of The Combination Of Everolimus (Rad001) With 5-Fu/Lv (De Gramont), Folfox6, And Folfox6/Panitumumab In Patients With Refractory Solid Malignancies

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving everolimus together with combination chemotherapy and/or panitumumab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with fluorouracil, leucovorin, panitumumab, and oxaliplatin in treating patients with solid tumors that did not respond to previous treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose of everolimus in combination with sequential fluorouracil (5-FU) and leucovorin calcium, panitumumab, modified 5-FU, leucovorin calcium, and oxaliplatin (mFOLFOX6), and mFOLFOX6 with panitumumab in patients with refractory solid tumors.

Secondary

  • To determine the adverse event profile of these regimens.
  • To correlate response with S6-phosphorylation and AKT-phosphorylation in available archived tumor samples.
  • To evaluate preliminary evidence of antitumor activity of these regimens using RECIST criteria for a subset of patients with measurable disease.

OUTLINE: This is a dose-escalation study. Cohorts of patients are enrolled into treatment groups 1 or 2. If a final cohort of patients is reached in groups 1 and/or 2, additional cohorts of patients are enrolled into treatment group 3.

  • Group 1: Patients receive oral everolimus once daily on days 1-28. Patients also receive leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
  • Group 2: Patients receive oral everolimus once daily on days 1-28 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
  • Group 3: Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Archived tumor samples are assessed for phospho-AKT, phospho-S6K, and phospho-S6 by immunohistochemistry.

After completion of study treatment, patients are followed every 3 months for 1 year.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant solid tumor

    • Advanced or unresectable disease
  • No standard therapeutic option available

  • Evaluable disease (according to RECIST criteria) that has not been previously irradiated

    • Prior radiotherapy to the marker lesion(s) allowed provided there is evidence of progression since radiotherapy

  • Brain metastases allowed provided the following criteria are met:

    • CNS-directed treatment was given and was completed > 3 months ago
    • CNS disease has been clinically and radiographically stable for ≥ 8 weeks

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/µL
  • Platelet count ≥ 100,000/µL
  • Creatinine clearance ≥ 60 mL/min
  • Total bilirubin ≤ 1.2 mg/dL
  • Transaminases ≤ 5 times upper limit of normal (ULN)
  • Magnesium ≥ lower limit of normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 24 weeks (females) or for 4 weeks (males) after completion of study therapy
  • Willing to avoid pregnancy for 3 months after completion of study therapy
  • No neuropathy ≥ grade 2
  • No concurrent life-threatening acute medical illness
  • No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • No active bleeding diathesis

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 3 weeks since prior major surgery, radiotherapy (including radiotherapy involving the abdomen or spine), chemotherapy, or other systemic anticancer therapy and recovered
  • At least 4 weeks since prior investigational drugs
  • No concurrent CYP3A4 inducers or inhibitors that cannot be substituted by a different agent
  • No concurrent oral anti-vitamin K medication (except for low-dose warfarin)
  • No concurrent colony stimulating factors during the first course of treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
Patients receive oral everolimus once daily on days 1-28. Patients also receive leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: leucovorin calcium
Given IV
Drug: fluorouracil
Given IV
Other Names:
  • 5FU
Drug: everolimus
Given orally
Other Names:
  • Afinitor
Experimental: Group 2
Patients receive oral everolimus once daily on days 1-28 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: everolimus
Given orally
Other Names:
  • Afinitor
Biological: panitumumab
Given IV
Other Names:
  • Vectibix
Experimental: Group 3
Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: oxaliplatin
Given IV
Other Names:
  • Eloxatin
Drug: leucovorin calcium
Given IV
Drug: fluorouracil
Given IV
Other Names:
  • 5FU
Drug: everolimus
Given orally
Other Names:
  • Afinitor
Biological: panitumumab
Given IV
Other Names:
  • Vectibix

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of everolimus in combination with sequential fluorouracil (5-FU) and leucovorin calcium, panitumumab, modified 5-FU, leucovorin calcium, and oxaliplatin (mFOLFOX6), and mFOLFOX6 with panitumumab
Time Frame: after the first 28 day cycle
Patients will be assessed for toxicity at the commencement of each cycle
after the first 28 day cycle
Toxicity as assessed by CTC version 3.0 at the beginning of each treatment course
Time Frame: first 28 day cycle
Dose Limiting Toxicities (DLT) are defined during the first cycle (28 days).
first 28 day cycle
Tumor response
Time Frame: Every 8 weeks during treatment
Tumor response will be assessed by RECIST criteria
Every 8 weeks during treatment
Correlation of response with S6-phosphorylation and AKT-phosphorylation in archived tumor samples
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Autumn McRee, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

February 7, 2008

First Submitted That Met QC Criteria

February 7, 2008

First Posted (Estimate)

February 8, 2008

Study Record Updates

Last Update Posted (Actual)

May 4, 2017

Last Update Submitted That Met QC Criteria

May 1, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCCC 0621
  • P30CA016086 (U.S. NIH Grant/Contract)
  • CDR0000584276 (Other Identifier: PDQ number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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