Metastatic colorectal cancer MedDRA version: 14.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Vectibix 20mg/ml concentrate for solution for infusion
Product Name: Panitumumab
Product Code: AMG 954
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Propose
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum • Wild-type KRAS tumor status of archival tumor tissue (preferably from the primary tumor) confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method • Radiographic evidence of disease progression while on or = 6 months after treatment with irinotecan- and oxaliplatin- or oxaliplatin-based chemotherapy for mCRC • Subjects in whom relapse is diagnosed within 6 months after completing adjuvant chemotherapy (with oxaliplatin-containing regimen) will be considered as having failed a prior regimen for metastatic disease. • Radiographic measurement of tumor burden done within 28 days prior to Day 1 (start of treatment with investigational product) • At least 1 uni-dimensionally measurable lesion = 20 mm using conventional CT or MRI or = 10 mm by spiral CT per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated • At least 1 tumor (metastatic lesion or unresected primary tumor) that is amenable to core needle biopsy, as determined by the clinician who will perform the biopsy • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix E) • Male or female = 18 years of age at the time of informed consent • Willing to undergo two core biopsy procedures of tumors (metastasis or unresected primary) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: • History of prior or concurrent central nervous system (CNS) metastases • Prior treatment with anti-EGFR antibodies (eg, panitumumab, cetuximab) or EGFR small molecule inhibitors (eg, erlotinib, gefitinib) • Prior treatment with monoclonal antibodies directed against IGF-1R or small molecule inhibitors directed against IGF-1R • Use of systemic chemotherapy and radiotherapy = 21 days before enrollment Subject must have recovered from acute toxicities related to radiotherapy. • Use of any antibody therapy (eg, bevacizumab) = 42 days before enrollment • Use of anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules = 30 days before enrollment • Known UGT1A1 polymorphisms predisposing to increased irinotecan toxicity • History of irinotecan intolerance that may interfere with planned treatment • History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan • Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection • Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion) • Any uncontrolled concurrent illness (eg, infection, bleeding diathesis) or history of any medical condition that may interfere with the interpretation of the study results • Major surgical procedure = 28 days before enrollment or minor surgical procedure = 14 days before enrollment. Subjects must have recovered from surgery related toxicities. Core biopsy, central venous catheter placement, fine needle aspiration, thoracentesis, or paracentesis is not considered a major or minor surgical procedure.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To determine if acquired resistance to panitumumab therapy in subjects with KRAS wildtype mCRC correlates with emergence of mutant KRAS tumors. (Acquired resistance is defined as disease progression on panitumumab and irinotecan that occurs after a period of disease response or stable disease on treatment with this regimen is observed and radiographically-confirmed.) Part 2: To determine if inhibition of the IGF-1R pathway with AMG 479 can overcome resistance to panitumumab therapy, as demonstrated by the objective response rate (ORR) to panitumumab and AMG 479 following disease progression on panitumumab and irinotecan.;Secondary Objective: Part 1: To determine ORR and other measures of efficacy (ie, TTR, DOR, PFS, OS) to panitumumab plus irinotecan To evaluate the safety of panitumumab and irinotecan Part 2: To determine measures of efficacy (ie, TTR, DOR, PFS, OS) of panitumumab plus AMG 479 To evaluate the safety of panitumumab and AMG 479;Primary end point(s): Emergence of Mutant KRAS: KRAS mutation status changed from wild-type at baseline to mutant at the time of the second biopsy following the radiographic evidence of acquired resistance to panitumumab plus irinotecan (Part 1). Objective Response Rate (ORR): Confirmed complete or partial response (per modified RECIST) to panitumumab and AMG 479 (Part 2);Timepoint(s) of evaluation of this end point: Part 1 - at the time of the second biopsy Part 2- The incidences of either a confirmed complete response (CR) or partial response (PR) per modified RECIST criteria v1.0 during the treatment of regimen 2. A confirmed CR requires 2 assessments of CR at least 28 days apart. A confirmed PR requires 2 assessments at least 28 days apart of CR or PR. All subjects that do not meet the criteria for a confirmed CR or PR by the analysis cut-off date will be considered non-responders. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: ORR (Part 1), Time to Response (TTR), Duration of Response (DOR), Progression free Survival (PFS), On-treatment PFS, and Overall Survival (OS) (both Part 1 and Part 2) • Safety: Incidence and severity of adverse events, significant changes in laboratory values, incidence of anti-antibody formation (both Part 1 and Part 2) Objective Response Rate (ORR) in Part 1: The incidences of either a confirmed complete response (CR) or partial response (PR) per modified RECIST criteria v1.0 during the treatment of regimen 1. A confirmed CR requires 2 assessments of CR at least 28 days apart. A confirmed PR requires 2 assessments at least 28 days apart of CR or PR. All subjects that do not meet the criteria for a confirmed CR or PR by the analysis cut-off date will be considered non-responders. • Progression-free survival (PFS): Time from the first dose of investigational product to the first date of disease progression per the modified RECIST criteria v1.0 or death prior to the earlier of the analysis data cutoff date, initiating a new line of anti-tumor therapy, and receiving study treatment in Part 2 where applicable. Subjects who have not progressed or died by the analysis cutoff date will be censored at their last evaluable disease assessment date • Overall survival (OS): Time from the first dose of investigational product to the date of death in both Part 1 and Part 2. Subjects who have not died by the analysis cutoff date will be censored at their last contact date. • Time to Response (TTR): Time from the first dose of the investigational product to the date of first confirmed objective response in both Part 1 and Part 2. Calculated only for those subjects with a confirmed objective response. • Duration of response (DOR): Time from the first confirmed objective response to disease progression per the modified RECIST criteria v1.0 in both Part 1 and Part 2. Subjects not meeting criteria for progression by the analysis cutoff date | — |
Countries
Belgium, France, Germany, Italy, Spain
Contacts
Public ContactIHQ Medical Information – Clinical
Amgen (EUROPE) GmbH
Outcome results
None listed