Everolimus, Fluorouracil, Leucovorin, Panitumumab, and Oxaliplatin in Treating Patients With Solid Tumors That Did Not Respond to Treatment - Full Text View

Sponsors and Collaborators:	UNC Lineberger Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00610948

Purpose

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.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: everolimus Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Drug: panitumumab	Phase I

MedlinePlus related topics: Calcium Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Fluorouracil Oxaliplatin Calcium gluconate Everolimus Panitumumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	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

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

Primary Outcome Measures:

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 [ Designated as safety issue: Yes ]
Toxicity as assessed by CTC version 3.0 at the beginning of each treatment course [ Designated as safety issue: Yes ]
Tumor response as assessed by RECIST criteria every 8 weeks during treatment [ Designated as safety issue: No ]
Correlation of response with S6-phosphorylation and AKT-phosphorylation in archived tumor samples [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	February 2008
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Experimental Patients receive oral everolimus once on days 1, 8, 15, and 22. 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: everolimus Given orally Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV
Group 2: Experimental Patients receive oral everolimus once on days 1, 8, 15, and 22 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 Drug: panitumumab Given IV
Group 3: Experimental 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: everolimus Given orally Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV Drug: panitumumab Given IV

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 on days 1, 8, 15, and 22. 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 on days 1, 8, 15, and 22 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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00610948

Sponsors and Collaborators

UNC Lineberger Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Bert H. O'Neil, MD

UNC Lineberger Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000584276, UNC-LCCC-0621
Study First Received:	February 7, 2008
Last Updated:	December 25, 2008
ClinicalTrials.gov Identifier:	NCT00610948
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Everolimus
Calcium, Dietary
Oxaliplatin
Fluorouracil
Leucovorin

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances

Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Therapeutic Uses
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on January 15, 2009