Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer
A Phase II Enrichment Study of Panitumumab as a Single Agent or in Combination With Trametinib in Anti-EGFR-Refractory Stage IV Colorectal Cancer Patients
2 other identifiers
interventional
59
1 country
1
Brief Summary
This phase II clinical trial studies how well panitumumab with or without trametinib works in treating patients with stage IV colorectal cancer. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving panitumumab with or without trametinib may work better in treating patients with stage IV colorectal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2017
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 10, 2017
CompletedFirst Posted
Study publicly available on registry
March 22, 2017
CompletedStudy Start
First participant enrolled
December 29, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
January 12, 2026
January 1, 2026
9.1 years
March 10, 2017
January 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Response rate
Will be evaluated along with the exact 95% confidence interval.
Up to 24 months
Secondary Outcomes (5)
Complete response
Up to 24 months
Partial response
Up to 24 months
Stable disease
Up to 24 months
Progression-free survival (PFS)
Up to 24 months
Overall survival (OS)
Up to 24 months
Study Arms (3)
Cohort 1 (panitumumab)
EXPERIMENTALPatients with EGFR ectodomain mutation receive panitumumab IV over 30-90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Cohort 2.
Cohort 2 (panitumumab, trametinib)
EXPERIMENTALPatients with KRAS, NRAS, or BRAF mutation receive trametinib PO QD on days 1-14 and panitumumab as in Cohort 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Cohort 3 (panitumumab)
EXPERIMENTALPatients without EGFR ectodomain, KRAS, NRAS, or BRAF mutation receive panitumumab as in Cohort 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Cohort 2.
Interventions
Correlative studies
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed colorectal adenocarcinoma, with metastatic disease documented on diagnostic imaging studies
- Progression during or within 6 months after fluoropyrimidine, irinotecan, and oxaliplatin; for oxaliplatin-based therapy, failure of therapy will also include patients who progressed within 12 months of adjuvant therapy and patients who had oxaliplatin discontinued secondary to toxicity or allergic reaction; patients with a known history of Gilbert's disease who cannot receive irinotecan or patients who are intolerant of irinotecan or fluoropyrimidine are eligible
- Confirmed wild-type status in KRAS exons 2, 3, and 4; NRAS exons 2, 3, and 4; and BRAF, by standard of care testing of tumor specimen; tissue used for testing may have been collected prior to treatment with anti-EGFR therapy
- Patient must have been already tested and have available results of the mutations status of KRAS/NRAS/BRAF/MEK (MAP2K1) and EGFR from the circulating tumor DNA within 10 weeks prior to starting study therapy
- Previous treatment with anti-EGFR therapy with evidence of clinical benefit, as defined by complete response, partial response, or prolonged stable disease with 16 or more weeks of treatment without radiographic progression, as assessed by the treating physician and documented in the medical record; this treatment may have occurred at any point in the patient's clinical course for treatment of metastatic colorectal cancer
- Ultimate progression through previous treatment with anti-EGFR therapy, with documented clinical progression; patients who discontinued anti-EGFR therapy for any other reason, such as decline in performance status, hypersensitivity, or other adverse effects of therapy, are not eligible
- All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) =\< grade 1 (except =\< grade 2 for alopecia peripheral neuropathy)
- Radiographically measurable disease present per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Blood counts performed within 3 weeks prior to starting study therapy must have absolute neutrophil count \>= 1,500/mm\^3
- Blood counts performed within 3 weeks prior to starting study therapy must have platelets \>= 100,000/mm\^3
- Blood counts performed within 3 weeks prior to starting study therapy must have hemoglobin \>= 9 g/dL
- Liver function tests performed within 3 weeks prior to starting study therapy must have total bilirubin =\< 1.5 x upper limit of normal (ULN)
- Liver function tests performed within 3 weeks prior to starting study therapy must have alanine aminotransferase and aspartate aminotransferase =\< 2.5 x ULN (or =\< 5 x ULN if liver metastases are present)
- Liver function tests performed within 3 weeks prior to starting study therapy must have albumin \>= 2.5 g/dL
- +9 more criteria
You may not qualify if:
- Past treatment with any MEK or ERK inhibitor
- Previous retreatment with anti-EGFR therapy following progression on initial course of anti-EGFR therapy
- Known untreated brain metastasis or brain metastasis treated within 3 months prior to enrollment in this trial
- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
- History of interstitial lung disease or pneumonitis
- History of any other malignancy within 3 years, except for adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer and/or subjects with indolent second malignancies are eligible
- Prior treatment within 21 days of the first dose of study drug with any other chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment, or failure to recover from adverse effects of prior therapies administered over 4 weeks prior to study day 1; all toxicities from prior therapies must be =\< grade 1 (or =\< grade 2 for alopecia or peripheral neuropathy); prior systemic treatment in the adjuvant setting is allowed
- Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to randomization and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to randomization
- Impaired cardiac function or clinically significant cardiac disease, as defined: a) left ventricular ejection fraction \< lower limit of normal (LLN) on multiple gated acquisition scan (MUGA) or echocardiogram; b) congenital long QT syndrome or family history of unexpected sudden cardiac death; c) corrected QT (QTc) corrected with Bazett's formula (QTcB) \>= 480 ms.; d) history or evidence of current clinically significant uncontrolled arrhythmias; note subjects with atrial fibrillation controlled for \> 30 days prior to dosing are eligible; e) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization; f) history or evidence of current \>= class II congestive heart failure as defined by New York Heart Association (NYHA); g) treatment refractory hypertension defined as a blood pressure of systolic \> 140 mmHg and/or diastolic \> 90 mm Hg which cannot be controlled by anti-hypertensive therapy; h) patients with intra-cardiac defibrillators
- Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent, or compliance to the study procedures
- History of retinal vein occlusion (RVO)
- Pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment
- History of organ allograft or other history of immunodeficiency
- Inability or unwillingness to comply with study and/or follow-up requirements
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO)
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christine Parseghian
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 10, 2017
First Posted
March 22, 2017
Study Start
December 29, 2017
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
January 12, 2026
Record last verified: 2026-01