- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00466505
Cetuximab & Celecoxib for Metastatic Colorectal Cancer or Colorectal Cancer That Cannot Be Removed by Surgery
A Phase 2 Study of Cetuximab in Combination With Celecoxib in Colorectal Cancer
RATIONALE: Monoclonal antibodies, such as cetuximab, 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. Cetuximab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cetuximab together with celecoxib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with celecoxib works in treating patients with metastatic colorectal cancer or colorectal cancer that cannot be removed by surgery.
Panoramica dello studio
Stato
Condizioni
Descrizione dettagliata
OBJECTIVES:
Primary
- Determine the time to progression in patients with unresectable or metastatic colorectal cancer treated with cetuximab and celecoxib.
Secondary
- Determine the response rate, median survival, and 1-year survival rate of patients treated with this regimen.
- Determine the toxicity profile of this regimen in these patients.
- Determine the feasibility of testing urinary PGE-M in patients treated with this regimen.
- Determine the feasibility of testing serum transforming growth factor-α and amphiregulin in patients treated with this regimen.
- Determine the effects of this regimen on the EGFR pathway in tumor cells (i.e., phosphorylated EGFr, phosphorylated AKT, activated mitogen-activated protein kinase).
- Determine the effects of this regimen on the cyclooxygenase-2 pathway in tumor cells by measuring PGE-2 levels.
OUTLINE: Patients receive cetuximab IV over 1-2 hours once weekly and oral celecoxib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Serum and urine samples are collected at baseline, after week 1, and every other course thereafter for evaluation of PGE-2 by mass spectrometry, cyclooxygenase-2 activity, and phospho-EGFR levels by western blot analysis and immunohistochemistry. Samples are also analyzed for TGF-α and amphiregulin proteomics.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
-
-
Tennessee
-
Nashville, Tennessee, Stati Uniti, 37232
- Vanderbilt-Ingram Cancer Center
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Patients must have histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > or equal to 20 mm with conventional techniques or as > or equal 10 mm with spiral CT scan.
- Patients must have progressed after at least 1 chemotherapy regimen for advanced disease. No prior therapy which specifically and directly targets the EGFR pathway.
- Age 18 years or older
- ECOG performance status ≤ 2.
- Life expectancy of greater than 3 months.
Normal organ and marrow functions as defined below:
- absolute neutrophil count ≤ 1,500/μl
- platelets ≤ 100,000/μl
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) > or equal to 2.5 times institutional upper limit of normal or > or equal to 5.0 times normal if liver metastases are present
- creatinine within normal institutional limits OR
- creatinine clearance > or equal to 60 mL/min/1.73 m2 for patients creatinine levels above institutional normal
- The effects of cetuximab and/or celecoxib on the developing human fetus at the recommended therapeutic doses are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to provide written informed consent.
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Prior severe infusion reaction to a monoclonal antibody
- Serum calcium >12.0 mg/dl.
- Patients must be off all other selective or non-selective COX-2 inhibitors for at least 2 weeks prior to study entry (with the exception of 81 mg of daily aspirin).
- No major surgery within 4 weeks. No minor surgery (laparoscopy, thoracoscopy, port placement) within 1 week.
- Patients must be > 4 weeks from prior pelvic radiation and recovered from side effects.
- Patients must be > 1 week from prior palliative radiation and have recovered from all side effects.
- Prior treatment with EGFR targeting therapies.
- Significant traumatic injury occurring within 28 days prior to treatment.
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because cetuximab is an epidermal growth factor inhibitor with the potential for teratogenic or abortifacient effects based on the data suggesting that EGFR expression is important for normal organ development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cetuximab, breastfeeding should be discontinued if the mother is treated with cetuximab.
- Patients with known HIV disease.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: Intervento terapeutico
|
400 mg/m2 iv week 1, then 250 mg/m2 weekly thereafter, starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.
Altri nomi:
200 mg po BID starting on day 1 and continuing until progressive disease, excessive toxicity or removal from study for other reasons listed in the protocol.
Altri nomi:
Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction.
We will use LC-MS-MS or MALDITOF mass spectrometry.
phospho-EGFR levels using western blots of tissue extracts and immunohistochemistry on frozen and (if no other option available, paraffinembedded tissue sections).
Serum samples obtained as above will be analyzed by proteomic analysis in order to determine biomarkers of treatment response and toxicity prediction.
We will use LC-MS-MS or MALDITOF mass spectrometry.
Before any tissues are received, the drug of interest is evaluated via MALDI mass spectrometry on a MDS/Sciex QStar QqTOF mass spectrometer.
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Progression-free Survival (PFS)
Lasso di tempo: On study date to off study date in this study with median 9.76 months
|
Number of days from study enrollment to evidence of progressive disease radiographically, with progression defined under RECIST criteria as at least 20% increase in sum of longest diameter of target lesions
|
On study date to off study date in this study with median 9.76 months
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Patient Response to Treatment
Lasso di tempo: On study date to off study date in this study with median 9.76 months
|
Number of patients in each response category according to RECIST criteria: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started.
Complete response (CR): disappearance of all target lesions.
Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD.
Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
|
On study date to off study date in this study with median 9.76 months
|
Overall Survival
Lasso di tempo: On study date to off study date in this study with median 9.76 months
|
Median survival time in months, from on-study date to date of death
|
On study date to off study date in this study with median 9.76 months
|
One Year Survival Rate
Lasso di tempo: 1 year from on-study date
|
Percent of patients who remain alive one year from on-study date
|
1 year from on-study date
|
Number of Patients With Each Worst-grade Toxicity Response
Lasso di tempo: On study date to off study date in this study with median 9.76 months
|
Number of patients with worst-grade toxicity response of each grade (grade 1 to 5) following NCI Common Toxicity Criteria, with grade 1=mild adverse event; 2=moderate adverse event; 3=severe and undesirable adverse event; 4=life-threatening or disabling adverse event; 5=death.
|
On study date to off study date in this study with median 9.76 months
|
Urinary PGE-M : Treatment Cycle 1
Lasso di tempo: on-study week 5
|
Measurement in ng/mL of a stable metabolite of prostaglandin E2 (PGE-M) in urine during treatment cycle 1
|
on-study week 5
|
Serum TGF-alpha: Treatment Cycle 1
Lasso di tempo: on-study week 5
|
Measurement in ng/mL of tumor growth factor-alpha (TGF-alpha) in serum samples during treatment cycle 1
|
on-study week 5
|
Urinary PGE-M : Treatment Cycle 2
Lasso di tempo: on-study week 9
|
Measurement in ng/mL of a stable metabolite of prostaglandin E2 (PGE-M) in urine during treatment cycle 2
|
on-study week 9
|
Serum TGF-alpha: Treatment Cycle 2
Lasso di tempo: on-study week 9
|
Measurement in ng/mL of tumor growth factor-alpha (TGF-alpha) in serum samples during treatment cycle 2
|
on-study week 9
|
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Jordan D. Berlin, MD, Vanderbilt-Ingram Cancer Center
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie dell'apparato digerente
- Neoplasie
- Neoplasie per sede
- Neoplasie gastrointestinali
- Neoplasie dell'apparato digerente
- Malattie gastrointestinali
- Malattie del colon
- Malattie intestinali
- Neoplasie intestinali
- Malattie del retto
- Neoplasie colorettali
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti del sistema nervoso periferico
- Inibitori enzimatici
- Analgesici
- Agenti del sistema sensoriale
- Agenti antinfiammatori, non steroidei
- Analgesici, non narcotici
- Agenti antinfiammatori
- Agenti antireumatici
- Inibitori della ciclossigenasi
- Agenti antineoplastici
- Agenti antineoplastici, immunologici
- Inibitori della cicloossigenasi 2
- Celecoxib
- Cetuximab
Altri numeri di identificazione dello studio
- VICC GI 0410
- P30CA068485 (Sovvenzione/contratto NIH degli Stati Uniti)
- VU-VICC-GI-0410
- VU-IRB-040227
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Cancro colorettale
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletatoAdenocarcinoma dell'intestino tenue | Adenocarcinoma dell'intestino tenue in stadio III AJCC v8 | Adenocarcinoma dell'intestino tenue in stadio IIIA AJCC v8 | Adenocarcinoma dell'intestino tenue in stadio IIIB AJCC v8 | Adenocarcinoma dell'intestino tenue stadio IV AJCC v8 | Ampolla di Vater... e altre condizioniStati Uniti
-
Georgetown UniversityNational Cancer Institute (NCI); American Cancer Society, Inc.; Susan G. Komen...CompletatoStudio delle donne cinesi che non hanno aderito alle linee guida per lo screening mammografico dell'American Cancer SocietyStati Uniti
-
National Cancer Institute (NCI)ReclutamentoKita-kyushu Lung Cancer Antigen 1, umanoStati Uniti
-
Novartis PharmaceuticalsReclutamentoEGFR mutante avanzato Non SmallSellLung Cancer (NSCLC), KRAS G12-mutant NSCLC, Esophageal SquamousCell Cancer (SCC), Head/Neck SCC, MelanomaOlanda, Corea, Repubblica di, Spagna, Taiwan, Giappone, Italia, Canada, Stati Uniti, Singapore
-
Emory UniversityNational Cancer Institute (NCI)RitiratoCancro al seno in stadio IV prognostico AJCC v8 | Neoplasia maligna metastatica nel cervello | Carcinoma mammario metastatico | Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8
-
NRG OncologyNational Cancer Institute (NCI)Attivo, non reclutanteCancro al seno in stadio anatomico IV AJCC v8 | Cancro al seno in stadio IV prognostico AJCC v8 | Neoplasia maligna metastatica nell'osso | Neoplasia maligna metastatica nei linfonodi | Neoplasia maligna metastatica nel fegato | Carcinoma mammario metastatico | Neoplasia maligna metastatica nel... e altre condizioniStati Uniti, Canada, Arabia Saudita, Corea, Repubblica di
-
Jonsson Comprehensive Cancer CenterNon ancora reclutamentoCarcinoma della prostata | Stadio IVB Cancro alla prostata American Joint Committee on Cancer (AJCC) v8Stati Uniti
-
Rashmi Verma, MDNational Cancer Institute (NCI)ReclutamentoCarcinoma prostatico resistente alla castrazione | Adenocarcinoma prostatico metastatico | Stadio IVB Cancro alla prostata American Joint Committee on Cancer (AJCC) v8Stati Uniti
-
Assiut UniversityNon ancora reclutamentoDeterminare l’incidenza cumulativa di AKI utilizzando i criteri KDIGO in pazienti pediatrici con tumori maligni presso il South Egypt Cancer Institute (SECI)
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)Attivo, non reclutanteStadio III Adenocarcinoma della prostata AJCC v7 | Stadio II Adenocarcinoma prostatico AJCC v7 | Fase I Adenocarcinoma della prostata American Joint Committee on Cancer (AJCC) v7Stati Uniti
Prove cliniche su cetuximab
-
University Medical Center GroningenUMC Utrecht; Erasmus Medical CenterReclutamentoCarcinoma a cellule squamose della testa e del collo | Valutazione del margineOlanda
-
West China HospitalFirst Affiliated Hospital of Chongqing Medical UniversityReclutamentoCancro del colon-retto | Capecitabina | CetuximabCina
-
Eben RosenthalNational Cancer Institute (NCI)TerminatoAdenocarcinoma pancreaticoStati Uniti
-
HiberCell, Inc.TerminatoCancro colorettaleStati Uniti, Porto Rico, Germania, Francia
-
Merck KGaA, Darmstadt, GermanyCompletatoCancro del colon-retto metastatico non trattato in precedenzaFrancia, Italia, Polonia, Germania, Hong Kong, Austria, Brasile, Israele, Grecia, Argentina, Tailandia, Belgio, Australia, Messico
-
Arbeitsgemeinschaft medikamentoese TumortherapieMerck Sharp & Dohme LLCCompletatoCancro colorettale metastaticoAustria
-
Cancer Institute and Hospital, Chinese Academy...Reclutamento
-
Amsterdam UMC, location VUmcRadboud University Medical Center; University Medical Center GroningenTerminatoCancro colorettale metastaticoOlanda
-
Poitiers University HospitalCompletatoCancro al colon metastaticoFrancia
-
Copenhagen University Hospital at HerlevSconosciuto