PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy

NCT00364013 | Completed Phase 3 Results DMC

• 1 other identifier: 20050203
• Study Type: interventional
• Target: 1,183
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine the treatment effect of panitumumab in combination with FOLFOX compared to FOLFOX alone as first line therapy for metastatic colorectal cancer

Conditions

Metastatic Colorectal Cancer

Keywords

Oncology; Cancer; metastatic colorectal cancer; EGFr; Panitumumab; Clinical Trail; Amgen

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival (PFS), assessed by central radiological assessment, was defined as the time from randomization to disease progression per modified response evaluation criteria in solid tumors (RECIST) criteria or death. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.

  From randomization until the data cutoff date of 30 September 2008. Maximum follow-up time was 109 weeks.

Secondary Outcomes (5)

• Overall Survival

  From randomization until the data cutoff date of 28 August 2009. Maximum time on follow-up was 153 weeks.

• Percentage of Participants With an Objective Response

  Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.

• Time to Progression

  From randomization until the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.

• Duration of Response

  Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.

• Number of Participants With Adverse Events (AEs)

  From randomization until the data cut-off date of 28 August 2009; Maximum time on follow-up was 153 weeks.

Study Arms (2)

FOLFOX + Panitumumab

EXPERIMENTAL

Participants received panitumumab, 6 mg/kg on Day 1 and FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or unacceptable toxicity.

Drug: Panitumumab; Drug: FOLFOX regimen

FOLFOX

ACTIVE COMPARATOR

Participants received FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or until unacceptable toxicity.

Drug: FOLFOX regimen

Interventions

Panitumumab DRUG

Panitumumab 6 mg/kg over on Day 1 of each 14-day cycle, just prior to the administration of chemotherapy.

Also known as: Vectibix®

FOLFOX + Panitumumab

FOLFOX regimen DRUG

The FOLFOX regimen consisted of oxaliplatin 85 mg/m\^2 intravenous (IV) infusion on Day 1, leucovorin, 200 mg/m\^2 (racemate) on Days 1 and 2 and 5-fluorouracil 400 mg/m\^2 IV bolus followed by 600 mg/m\^2 IV infusion over 22 hours on Days 1 and 2. Each cycle was 14 days.

FOLFOX; FOLFOX + Panitumumab

Eligibility Criteria

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

You may qualify if:

• Man or woman at least 18 years old
• Diagnosis of metastatic colorectal cancer
• At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

You may not qualify if:

• History or known presence of central nervous system (CNS) metastases
• History of another primary cancer, except: Curatively treated in situ cervical cancer, or Curatively resected non-melanoma skin cancer, or Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization
• Prior chemotherapy or systemic therapy for the treatment of metastatic colorectal carcinoma except: adjuvant fluoropyrimidine-based chemotherapy or prior fluoropyrimidine therapy administered solely for the purpose of radiosensitization
• Prior oxaliplatin therapy
• Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, erlotinib)
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 1 year prior to randomization History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
• Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as \> Common terminology criteria (CTC) grade 2 \[CTCAE version 3.0\])
• Peripheral sensory neuropathy with functional impairment

Sponsors & Collaborators

• Amgen: lead

Related Publications (15)

• Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275.

  PMID: 24024839 BACKGROUND

• Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jul;25(7):1346-1355. doi: 10.1093/annonc/mdu141. Epub 2014 Apr 8.

  PMID: 24718886 BACKGROUND

• Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.

  PMID: 20921465 BACKGROUND

• Douillard JY, Siena S, Peeters M, Koukakis R, Terwey JH, Tabernero J. Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer. Eur J Cancer. 2015 Jul;51(10):1231-42. doi: 10.1016/j.ejca.2015.03.026. Epub 2015 May 5.

  PMID: 25956209 BACKGROUND

• Liu J, Wang X, Sahin IH, Imanirad I, Felder SI, Kim RD, Xie H. Tumor Response-speed Heterogeneity as a Novel Prognostic Factor in Patients With Metastatic Colorectal Cancer. Am J Clin Oncol. 2023 Feb 1;46(2):50-57. doi: 10.1097/COC.0000000000000972. Epub 2022 Dec 26.

  PMID: 36606664 DERIVED

• Taieb J, Geissler M, Rivera F, Karthaus M, Wilson R, Loupakis F, Price T, Tracy M, Burdon P, Peeters M. Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials. Clin Colorectal Cancer. 2019 Dec;18(4):245-256.e5. doi: 10.1016/j.clcc.2019.07.009. Epub 2019 Jul 29.

  PMID: 31515083 DERIVED

• Abdel-Rahman O. Effect of Body Mass Index on 5-FU-Based Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer; A Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Dec;18(4):e385-e393. doi: 10.1016/j.clcc.2019.07.005. Epub 2019 Jul 15.

  PMID: 31378656 DERIVED

• Abdel-Rahman O. Impact of Sex on Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer: Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Jun;18(2):110-115.e2. doi: 10.1016/j.clcc.2018.12.006. Epub 2018 Dec 28.

  PMID: 30679026 DERIVED

• Modest DP, Rivera F, Bachet JB, de Braud F, Pietrantonio F, Koukakis R, Demonty G, Douillard JY. Panitumumab-based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials. Int J Cancer. 2019 Jul 15;145(2):576-585. doi: 10.1002/ijc.32110. Epub 2019 Jan 24.

  PMID: 30614531 DERIVED

• Udar N, Lofton-Day C, Dong J, Vavrek D, Jung AS, Meier K, Iyer A, Slaughter R, Gutekunst K, Bach BA, Peeters M, Douillard JY. Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study. J Cancer Res Clin Oncol. 2018 Oct;144(10):2001-2010. doi: 10.1007/s00432-018-2688-3. Epub 2018 Jul 17.

  PMID: 30019318 DERIVED

• Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, Tabernero J, Douillard JY, Andre T, Peeters M. Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies. Clin Colorectal Cancer. 2018 Sep;17(3):170-178.e3. doi: 10.1016/j.clcc.2018.03.005. Epub 2018 Mar 8.

  PMID: 29627309 DERIVED

• Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, Tabernero J, Douillard JY, Andre T, Peeters M. Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol. 2017 Aug 1;28(8):1862-1868. doi: 10.1093/annonc/mdx119.

  PMID: 28449055 DERIVED

• Siena S, Tabernero J, Bodoky G, Cunningham D, Rivera F, Ruff P, Canon JL, Koukakis R, Demonty G, Hechmati G, Douillard JY. Quality of life during first-line FOLFOX4+/-panitumumab in RAS wild-type metastatic colorectal carcinoma: results from a randomised controlled trial. ESMO Open. 2016 Mar 31;1(2):e000041. doi: 10.1136/esmoopen-2016-000041. eCollection 2016.

  PMID: 27843597 DERIVED

• Peeters M, Kafatos G, Taylor A, Gastanaga VM, Oliner KS, Hechmati G, Terwey JH, van Krieken JH. Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials. Eur J Cancer. 2015 Sep;51(13):1704-13. doi: 10.1016/j.ejca.2015.05.017. Epub 2015 Jun 3.

  PMID: 26049686 DERIVED

• Weeraratne D, Chen A, Pennucci JJ, Wu CY, Zhang K, Wright J, Perez-Ruixo JJ, Yang BB, Kaliyaperumal A, Gupta S, Swanson SJ, Chirmule N, Starcevic M. Immunogenicity of panitumumab in combination chemotherapy clinical trials. BMC Clin Pharmacol. 2011 Nov 9;11:17. doi: 10.1186/1472-6904-11-17.

  PMID: 22070868 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Interventions

Panitumumab; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2006
• First Posted: August 15, 2006
• Study Start: August 1, 2006
• Primary Completion: August 1, 2009
• Study Completion: March 22, 2013
• Last Updated: November 7, 2022
• Results First Posted: March 28, 2014

Record last verified: 2022-11