Panitumumab, Leucovorin Calcium, and Fluorouracil after Combination Chemotherapy and Panitumumab Induction in Treating Patients with RAS Wild Type Locally Advanced or Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

Status: Active

Description

This randomized phase III trial studies how well panitumumab, leucovorin calcium, and fluorouracil after combination chemotherapy and panitumumab induction work in treating patients with RAS wild type colorectal cancer that has spread from where it started to nearby tissue or lymph nodes or other places in the body or cannot be removed by surgery. Immunotherapy with panitumumab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab, leucovorin calcium, and fluorouracil after combination chemotherapy and panitumumab induction may work better in treating patients with colorectal cancer.

Eligibility Criteria

Inclusion Criteria

  • Metastatic or locally advanced (unresectable) colorectal cancer with histological confirmation of adenocarcinoma (patients with or without measurable disease by imaging are eligible)
  • No prior systemic chemotherapy for metastatic disease; subjects who received adjuvant therapy with FOLFOX and at the time of recurrence are at least 6 months away from last chemotherapy are eligible for this study
  • Provide written informed consent
  • RAS wild‐type tumor
  • Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only * Childbearing potential is defined as a female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not postmenopausal (defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level > 35 mIU/mL); women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of childbearing potential
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1
  • Total serum bilirubin =< institutional upper limit of normal (ULN) (=< 14 days prior to on study [start of FOLFOX + panitumumab])
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (=< 14 days prior to on study [start of FOLFOX + panitumumab])
  • Platelet count >= 100,000/mm^3 (=< 14 days prior to on study [start of FOLFOX + panitumumab])
  • Hemoglobin >= 9.0 g/dL (hemoglobin may be supported by transfusion) (=< 14 days prior to on study [start of FOLFOX + panitumumab])
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (=< 14 days prior to on study [start of FOLFOX + panitumumab])
  • Creatinine within institutional limits of normal OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (=< 14 days prior to on study [start of FOLFOX + panitumumab])
  • Magnesium >= lower limit of normal (=< 14 days prior to on study [start of FOLFOX + panitumumab])
  • Willing to provide tissue and blood samples for mandatory correlative and research purposes

Exclusion Criteria

  • Patients who are candidates for up front metastasectomy * Defined as those with limited liver metastatic disease; the candidacy for resectability can be determined by the treating physician and or local surgeon; in ambiguous situations, please discuss the case with the principle investigator (PI)
  • Known or suspected brain or central nervous system (CNS) metastases
  • Active, uncontrolled infection, including hepatitis B, hepatitis C
  • Patients with history of interstitial lung disease/pulmonary fibrosis
  • Concurrent anti‐cancer therapy, including chemotherapy agents, targeted agents, or biological agents not otherwise specified in this protocol
  • Radiation therapy =< 2 weeks prior to initiation of FOLFOX + panitumumab
  • Any of the following * Pregnant or nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co‐morbid systemic illnesses or other severe concurrent disease, history of any psychiatric or addictive disorder, or laboratory abnormality, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Patients known to be human immunodeficiency virus (HIV) positive
  • Uncontrolled intercurrent illness whom in the opinion of the investigator, may increase the risks associated with study participation or study treatment, or may interfere with the conduct of the study or the interpretation of the study results
  • Receiving any other investigational agent, which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =< 3 years prior to registration; exceptions are: non-melanoma skin cancer or carcinoma‐in‐situ of the cervix that has been treated
  • History of prior malignancy for which patient is receiving other specific treatment for their cancer
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs

Locations & Contacts

California

Los Angeles
Los Angeles County-USC Medical Center
Status: Active
Contact: Afsaneh Barzi
Phone: 323-865-3829
Email: afsaneh.barzi@med.usc.edu
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Afsaneh Barzi
Phone: 323-865-3829
Email: Afsaneh.Barzi@med.usc.edu
Newport Beach
USC Norris Oncology / Hematology-Newport Beach
Status: Active
Contact: Greg Richard Angstreich
Phone: 949-646-6441
Email: greg.angstreich@usc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To compare the duration of progression free survival 1 (PFS1) in patients with RAS wild type who have received induction leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) + panitumumab and not progressed at 6 cycles and randomized to maintenance therapy with fluorouracil (5FU) based therapy with or without panitumumab.

SECONDARY OBJECTIVES:

I. To compare the response rate (RR) in patients with RAS wild type who are randomized to maintenance therapy with 5FU based therapy to those randomized to 5FU based therapy with panitumumab.

TERTIARY OBJECTIVES:

I. Progress free survival 2 (PFS2).

II. To assess the adverse event (AE) profile and safety of the proposed treatment in this population.

III. To assess and compare the overall survival (OS) between the two treatment groups.

IV. To compare the quality of life (QOL) as measured by EuroQoL 5‐domain (EQ‐5D) between patients who achieve partial response (PR) versus (vs.) those who progress and those who have stable disease during the induction phase.

V. To compare the QOL as measured by health state index (HSI) between the two groups randomized to maintenance therapy.

VI. To assess the evolution of RAS mutation under treatment during induction phase as well as maintenance.

VII. To explore relationship between genomic and proteomic alterations of the tumor with response and PFS to panitumumab.

OUTLINE:

INDUCTION:

Patients receive panitumumab intravenously (IV) over 30-60 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients who are not candidates for surgery, have no disease progression, or do not have complete response after Induction are randomized to 1 of 2 arms.

ARM I: Patients receive panitumumab IV over 30 minutes, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-21, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Cycles repeat every 21 days for capecitabine and every 14 days for leucovorin calcium and fluorouracil in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 28 days, then every 6 months.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
USC / Norris Comprehensive Cancer Center

Principal Investigator
Afsaneh Barzi

Trial IDs

Primary ID 3C-16-6
Secondary IDs NCI-2017-01414
Clinicaltrials.gov ID NCT03300609