Clinical trial NCT01801904: A Phase 2 Study of Panitumumab in Patients With Cetuximab-refractory Metastatic Colorectal Cancer
Official title: A Phase 2 Study of Panitumumab in Patients With Cetuximab-refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: cetuximab-refractory
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera G. Rummo
First posted: 2013-03-01
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess if panitumumab is active enough to warrant comparative studies in patients with metastatic colorectal cancer that has progressed after treatment with cetuximab.

Detailed description: The study was amended with modification of inclusion criteria (from wild-type tumor KRAS gene to wild-type RAS gene, including KRAS and NRAS exons 2, 3 and 4)

RAS mutational status of tumors of patients enrolled before amendment 1 approval will be centrally revised. Patients whose tumors will result RAS mutated at the biomarkers central revision, will be replaced. Therefore, the overall sample size at both the stages may be higher than the one initially planned.

Eligibility criteria: Inclusion Criteria:

* Pathologic diagnosis of metastatic colorectal adenocarcinoma
* a wild-type RAS tumor (mutational status has to be determined by an experienced laboratory using validated test methods for detection of KRAS exons 2, 3, and 4, and NRAS exons 2, 3, and 4
* Failure from previous treatment with fluoropyrimidine, oxaliplatin and irinotecan. Patients may or may not have been treated with bevacizumab.
* Documented disease progression following a treatment with cetuximab in patients who showed either an objective response after 8 weeks or stable disease after 16 weeks of cetuximab treatment.
* Age at least 18 years
* ECOG Performance Status 0-2
* Neutrophils at least 1,500 mm3, platelets at least 100,000 mm3, and hemoglobin at least 9 g/dL
* Bilirubin level less than 1.5 times ULN
* AST (SGOT) and ALT (SGPT) not greater than 2.5 times ULN (or 5 times ULN in presence of liver metastasis)
* Serum creatinine less than 1.5 times ULN
* Effective contraception, if the risk of conception exists
* Life expectancy at least 3 months
* Written informed consent

Exclusion Criteria:

* Symptomatic brain metastasis
* Interstitial pneumonitis or pulmonary fibrosis
* Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or non melanoma skin cancer)
* Chemotherapy, radiotherapy or immunotherapy within the past 4 weeks
* Any unstable systemic disease (including active infections, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study drugs or render the patient at high risk from treatment complications
* Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment

Primary outcomes:
measure: number of patients alive and without disease progression
timeFrame: 2 months
Secondary outcomes:
measure: response rate
timeFrame: up to 40 weeks
measure: progression free survival
timeFrame: 9 months
measure: overall survival
timeFrame: one year
measure: worst grade toxicity per patient
timeFrame: every 2 weeks for up to 6 months
Other outcomes:
measure: gene expression on tumor tissue
timeFrame: one year
Locations:
city: Benevento
country: Italy
facility: Azienda Ospedaliera G. Rummo
state: BN
city: Benevento
country: Italy
facility: Ospedale Fatebenefratelli
city: Napoli
country: Italy
facility: A.O.U. Policlinico Federico II
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori
city: S. Giovanni Rotondo
country: Italy
facility: Casa Sollievo Sofferenza
Study officials:
affiliation: Azienda Sanitaria Rummo, Benevento, Division of Medical Oncology
name: Bruno Daniele, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute Naples, Italy; Director Clinical Trials Unit
name: Francesco Perrone, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Second University of Naples, Italy; Chair of Medical Statistics
name: Ciro Gallo, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Università Cattolica del S. Cuore, Policlinico Gemelli, Roma
name: Antonio Gasbarrini, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Antonio Cardarelli, Napoli
name: Giacomo Carteni', M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Piccirillo MC, Avallone A, Carlomagno C, Maiello E, Rosati G, Alabiso O, Nasti G, De Placido S, Latiano TP, Bilancia D, Ottaiano A, De Stefano A, Romano C, Silvestro L, Nappi A, Cassata A, Giordano P, Iaffaioli RV, Normanno N, Perrone F, Daniele B. Multicenter Single-Arm, Two-Stage Phase 2 Study of Panitumumab in Patients With Cetuximab-Refractory Metastatic Colorectal Cancer: The PACER Trial. Clin Colorectal Cancer. 2020 Dec;19(4):270-276. doi: 10.1016/j.clcc.2020.05.009. Epub 2020 May 29.