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5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

Primary Purpose

Colorectal Adenocarcinoma, RAS Wild Type, Stage III Colorectal Cancer AJCC v7

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Panitumumab
Oxaliplatin
Leucovorin Calcium
Fluorouracil
Capecitabine
Quality-of-Life Assessment
Laboratory Biomarker Analysis
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • At the time of randomization to maintenance therapy only patients who didn't progress by Response Evaluation Criteria in Solid Tumors (RECIST) criteria are eligible; patients with complete response (CR) and those who are candidates for resection will not be eligible for randomization to maintenance therapy, subjects who undergo surgery potentially have curable disease with defined duration of treatment and use of EGFR in the adjuvant setting is deemed to be detrimental in these population; likelihood of achieving CR is low and standard of care in this unique patient population is not well defined
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1
  • Total serum bilirubin =< institutional upper limit of normal (ULN)
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9.0 g/dL (hemoglobin may be supported by transfusion)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
  • Creatinine within institutional limits of normal OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Magnesium >= lower limit of normal
  • Willing to provide tissue and blood samples for mandatory correlative and research purposes

Exclusion Criteria:

  • Patients who are candidates for upfront metastasectomy (defined as those with limited liver metastatic disease) are not eligible for this study; 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 randomization

  • 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: nonmelanoma 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

Sites / Locations

  • USC/Norris Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (panitumumab, leucovorin calcium, fluorouracil)

Arm II (capecitabine)

Arm Description

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

INDUCTION Patients receive panitumumab 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 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive capecitabine PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Progression free survival 1
Disease progression will be determined by comparing tumor measurement during maintenance therapy to baseline measurement before starting maintenance treatment using Response Evaluation Criteria in Solid Tumors 1.1. will be conducted based on the intent-to-treat population from the time of randomization.

Secondary Outcome Measures

Treatment Response
Response will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1)

Full Information

First Posted
September 28, 2017
Last Updated
June 8, 2020
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI), Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT03300609
Brief Title
5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab
Official Title
Randomized Phase III Trial of 5-FU Based Maintenance Therapy With or Without Panitumumab in Patients With RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX + Panitumumab
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
Insufficient Accrual
Study Start Date
February 27, 2018 (Actual)
Primary Completion Date
October 3, 2019 (Actual)
Study Completion Date
October 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI), Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized 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. Monoclonal antibodies, such as panitumumab, 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.
Detailed Description
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 health state index (HIS) 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 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 courses 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. Courses 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. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Adenocarcinoma, RAS Wild Type, Stage III Colorectal Cancer AJCC v7, Stage IIIA Colorectal Cancer AJCC v7, Stage IIIB Colorectal Cancer AJCC v7, Stage IIIC Colorectal Cancer AJCC v7, Stage IV Colorectal Cancer AJCC v7, Stage IVA Colorectal Cancer AJCC v7, Stage IVB Colorectal Cancer AJCC v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (panitumumab, leucovorin calcium, fluorouracil)
Arm Type
Experimental
Arm Description
INDUCTION Patients receive panitumumab 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 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive panitumumab IV over 30 minutes, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II (capecitabine)
Arm Type
Active Comparator
Arm Description
INDUCTION Patients receive panitumumab 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 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive capecitabine PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
339177-26-3, ABX-EGF, ABX-EGF Monoclonal Antibody, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, Vectibix
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
1-OHP, 266046, 61825-94-3, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, oxalato (1R,2R-cyclohexanediamine)platinum(II), oxalato (trans-l-1,2-diaminocyclohexane)platinum(II), Oxalatoplatin, Oxalatoplatinum, RP-54780, SR-96669, trans-l DACH oxalatoplatinum, trans-l diaminocyclohexane oxalatoplatinum
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Leucovorin Calcium
Other Intervention Name(s)
1492-18-8, 5-Formyl Tetrahydrofolate, 5-Formyl-5,6,7,8-tetrahydrofolic Acid, 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid, Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Fusilev, Lederfolat, Lederfolin, Leucosar, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
19893, 2,4-Dioxo-5-fluoropyrimidine, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluoro-2,4(1H,3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, 51-21-8, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
154361-50-9, 5'-Deoxy-5-fluoro-N-[(pentyloxy)carbonyl]-cytidine, 712807, Ro 09-1978/000, Xeloda
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Progression free survival 1
Description
Disease progression will be determined by comparing tumor measurement during maintenance therapy to baseline measurement before starting maintenance treatment using Response Evaluation Criteria in Solid Tumors 1.1. will be conducted based on the intent-to-treat population from the time of randomization.
Time Frame
From the date of randomization to the date of 1st documented disease progression or death due to any cause, whichever occurs first, assessed up to 7 months.
Secondary Outcome Measure Information:
Title
Treatment Response
Description
Response will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1)
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 At the time of randomization to maintenance therapy only patients who didn't progress by Response Evaluation Criteria in Solid Tumors (RECIST) criteria are eligible; patients with complete response (CR) and those who are candidates for resection will not be eligible for randomization to maintenance therapy, subjects who undergo surgery potentially have curable disease with defined duration of treatment and use of EGFR in the adjuvant setting is deemed to be detrimental in these population; likelihood of achieving CR is low and standard of care in this unique patient population is not well defined 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 Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1 Total serum bilirubin =< institutional upper limit of normal (ULN) Absolute neutrophil count (ANC) >= 1500/mm^3 Platelet count >= 100,000/mm^3 Hemoglobin >= 9.0 g/dL (hemoglobin may be supported by transfusion) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) Creatinine within institutional limits of normal OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Magnesium >= lower limit of normal Willing to provide tissue and blood samples for mandatory correlative and research purposes Exclusion Criteria: Patients who are candidates for upfront metastasectomy (defined as those with limited liver metastatic disease) are not eligible for this study; 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 randomization 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: nonmelanoma 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Afsaneh Barzi, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

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