Ph2 Biomarker (Mechanism of K-ras Dependency) in Wt KRAS Metastatic Colorectal Cancer Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00891930
First received: March 12, 2009
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

This is a global, multicenter, open-label phase 2 study designed to evaluate the mechanism(s) of resistance to the anti-EGFR (epidermal growth factor receptor) antibody panitumumab given in combination with irinotecan in mCRC (metastatic colorectal carcinoma) subjects with wild-type KRAS (Kirsten rat Sarcoma-2 virus) tumor status at the time of initial diagnosis. In Part 1, all subjects will undergo a baseline tumor biopsy and will receive panitumumab with irinotecan. Subjects that respond or have stable disease will continue to receive treatment until radiographically-confirmed disease progression. These subjects will then undergo a second tumor biopsy and blood sampling and then proceed to Part 2 of the study. In Part 2, all subjects will receive panitumumab with AMG 479. In both parts of the study, panitumumab and irinotecan (Part 1) and panitumumab and AMG 479 (Part 2) will be administered every 2 weeks until disease progression, intolerability, withdrawal of consent, death, or unless otherwise indicated by the study team.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Panitumumab
Drug: AMG 479
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Panitumumab Plus Irinotecan Followed by Panitumumab Plus AMG 479 in Subjects With Metastatic Colorectal Carcinoma Expressing Wild Type KRAS and Refractory to Oxaliplatin-or Irinotecan- and Oxaliplatin-containing Regimens to Evaluate Mechanisms of Acquired Resistance to Panitumumab

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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 disease resistance to panitumumab given in combination with irinotecan (Part 1) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR) in Part 2: Confirmed complete or partial response (per modified RECIST) to panitumumab and AMG 479 (Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective Response Rate (Part 1) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • Time to Response (TTR) (both Part 1 and Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • Progression-free Survival (PFS) (both Part 1 and Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • Overall Survival (OS) (both Part 1 and Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events (both Part 1 and Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • significant changes in laboratory values (both Part 1 and Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • incidence of anti-antibody formation (both Part 1 and Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) (both Part 1 and Part 2) [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]

Enrollment: 76
Study Start Date: May 2009
Study Completion Date: October 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 Drug: Panitumumab
Panitumumab 6mg/kg will be administered via IV infusion is over 60 minutes +/- 15 minutes
Drug: Irinotecan
Irinotecan starting dose of 180mg/m2 will be adminstered via IV infusion on day 1 of each cycle of Part 1 following completion of panitumumab infusion and proper flushing of the infusion line. Irinotecan should be obtained by each site as per routine institutional practice.
Experimental: Part 2 Drug: Panitumumab
Panitumumab 6mg/kg will be administered via IV infusion is over 60 minutes +/- 15 minutes
Drug: AMG 479
AMG 479 12mg/kg will be adminstered by IV infusion over 60 +/- 15minutes

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum; Subjects with wild-type KRAS tumor status confirmed by an Amgen approved central laboratory assessment or an experienced local laboratory assessment of archival tumor tissue (preferably from the primary tumor); Radiographic evidence of disease progression while on or ≤ 6months after completion of treatment with irinotecan- and oxaliplatin- or oxaliplatin-based chemotherapy for mCRC; 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 scan per modified RECIST v1.0. 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 (preferably a metastasis or unresected primary tumour) that is amenable to core biopsy, as determined by the clinician who will perform the biopsy; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Male or female ≥ 18 years of age at the time of informed consent; A life expectancy estimate of ≥ 3 months; Willing to undergo two serial core biopsy procedures of tumors (metastasis or unresected primary); other criteria may apply Exclusion Criteria: History of other primary cancer, unless: Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician, Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease, Adequately treated cervical carcinoma in situ without evidence of disease, Prostatic intraepithelial neoplasia without evidence of prostate cancer; History of prior or concurrent central nervous system (CNS) metastases; Prior treatment with anti-EGFR (eg, panitumumab, cetuximab or small molecule inhibitors (eg, erlotinib, gefitinib); Prior treatment with monoclonal antibodies directed against insulin-like growth factor-1 receptor (IGF-1R) or small molecule inhibitors directed against IGF-1R; Use of systemic chemotherapy or radiotherapy ≤ 21 days before enrollment. Subjects must have recovered from acute toxicities related to radiotherapy; Use of any antibody therapy (eg, bevacizumab) ≤ 42 days before enrolment; Use of anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrolment; Known allergy or hypersensitivity to any component of panitumumab, irinotecan, or AMG 479; Known uridine diphosphate glucuronosyltransferase 1A1 (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; Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment; Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) version 3.0); Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection; 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; Other investigational procedures or drugs (ie, participation in another clinical study) ≤ 30 days before enrolment; other criteria may apply

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00891930

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00891930     History of Changes
Other Study ID Numbers: 20070820
Study First Received: March 12, 2009
Last Updated: April 23, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
Italy: Ministry of Health
Spain: Spanish Drug Agency
United States: Food and Drug Administration

Keywords provided by Amgen:
wild-type KRAS
panitumumab
biomarker
mechanisms of acquired resistance
metastatic colorectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014