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

NCT00610948 | Completed Phase 1 DMC

• 3 other identifiers: LCCC 0621P30CA016086CDR0000584276
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (4)

• 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

  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

  Dose Limiting Toxicities (DLT) are defined during the first cycle (28 days).

  first 28 day cycle

• Tumor response

  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

  3 years

Study Arms (3)

Group 1

EXPERIMENTAL

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: everolimus; Drug: fluorouracil; Drug: leucovorin calcium

Group 2

EXPERIMENTAL

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.

Biological: panitumumab; Drug: everolimus

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.

Biological: panitumumab; Drug: everolimus; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

Interventions

panitumumab BIOLOGICAL

Given IV

Also known as: Vectibix

Group 2; Group 3

everolimus DRUG

Given orally

Also known as: Afinitor

Group 1; Group 2; Group 3

fluorouracil DRUG

Given IV

Also known as: 5FU

Group 1; Group 3

leucovorin calcium DRUG

Given IV

Group 1; Group 3

oxaliplatin DRUG

Given IV

Also known as: Eloxatin

Group 3

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Related Publications (1)

• McRee AJ, Davies JM, Sanoff HG, Goldberg RM, Bernard S, Dees EC, Keller K, Ivanova A, O'Neil BH. A phase I trial of everolimus in combination with 5-FU/LV, mFOLFOX6 and mFOLFOX6 plus panitumumab in patients with refractory solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):117-23. doi: 10.1007/s00280-014-2474-0. Epub 2014 May 13.

  PMID: 24819684 DERIVED

Related Links

• web address for the National Cancer Institute (NCI)
• web address for the Lineberger Comprehensive Cancer Center, UNC

MeSH Terms

Interventions

Panitumumab; Everolimus; Fluorouracil; Leucovorin; Oxaliplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes

Study Officials

• Autumn McRee, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2008
• First Posted: February 8, 2008
• Study Start: March 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: January 1, 2016
• Last Updated: May 4, 2017

Record last verified: 2017-05

Locations

US (1)