Study to Evaluate the Effects of Panitumumab if Combined With Chemotherapy for 2nd Treatment of Colorectal Cancer (VOXEL)

This study has been terminated.
(Recruitment rate to low; changed environment made protocol in its current state obsolete)
Sponsor:
Collaborator:
iOMEDICO AG
Information provided by (Responsible Party):
AIO-Studien-gGmbH
ClinicalTrials.gov Identifier:
NCT00950820
First received: July 31, 2009
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

The purpose of this interventional study is to investigate whether there is evidence that panitumumab in combination with XELOX (capecitabine plus oxaliplatin) chemotherapy will safely increase progression-free survival, above that of XELOX alone in subjects with KRAS wild-type metastatic colorectal cancer who have not responded to or progressed after first line therapy with irinotecan and a fluoropyrimidine.

Further Objectives Exploratory objectives may include investigation of potential correlations between the treatment regimen and epidermal growth factor receptor (EGFR) expression, detection of the functional genetic polymorphisms of the EGFR gene, EGFR gene amplification (FISH), EGFR downstream protein and gene expression parameters, proteomics and epigenetics.


Condition Intervention Phase
Colorectal Neoplasms
Drug: Oxaliplatin, Capecitabine, Panitumumab
Drug: Oxaliplatin, Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Randomized Phase II Study of Panitumumab Plus Oral Capecitabine and Infusional Oxaliplatin (XELOX) or XELOX Alone for Second-line Treatment of Patients With Metastatic Colorectal Cancer (VOXEL-Study)

Resource links provided by NLM:


Further study details as provided by AIO-Studien-gGmbH:

Primary Outcome Measures:
  • Progression-free survival rate at 6 months for subjects with KRAS wild-type tumours [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PFS [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • Objective-response-rate [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • Disease-control-rate [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • Time-to-response [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • time-to-progression [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • duration-of-stable-disease [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • time-to-treatment-failure [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • overall-survival [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • safety-endpoints [ Time Frame: end of study ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: September 2009
Study Completion Date: March 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panitumumab + XELOX
KRAS mutational status wild-type: Panitumumab plus Oxaliplatin and Capecitabine (XELOX)
Drug: Oxaliplatin, Capecitabine, Panitumumab

Panitumumab at a dose of 9 mg/kg BW every three weeks will be administered on day 1 of each cycle just prior to administration of chemotherapy.

The XELOX regimen is defined as a 2 hour infusion of oxaliplatin 130 mg/m² on day 1 followed by capecitabine 1000 mg/m² bid per os. Capecitabine administration will commence on the evening of day 1 and complete after the morning dose on day 15.

XELOX (KRAS mutational status wt)
KRAS mutational status wild-type: Oxaliplatin and Capecitabine (XELOX)
Drug: Oxaliplatin, Capecitabine
The XELOX regimen is defined as a 2 hour infusion of oxaliplatin 130 mg/m² on day 1 followed by capecitabine 1000 mg/m² bid per os. Capecitabine administration will commence on the evening of day 1 and complete after the morning dose on day 15.
XELOX (KRAS mutational status mutant)
KRAS mutational status mutant: Oxaliplatin and Capecitabine (XELOX)
Drug: Oxaliplatin, Capecitabine
The XELOX regimen is defined as a 2 hour infusion of oxaliplatin 130 mg/m² on day 1 followed by capecitabine 1000 mg/m² bid per os. Capecitabine administration will commence on the evening of day 1 and complete after the morning dose on day 15.

Detailed Description:

Subjects with metastatic colorectal cancer with KRAS-wildtype will be randomized in a 1:1 ratio to receive a 2nd line treatment regimen of panitumumab plus oxaliplatin and capecitabine (XELOX) or XELOX alone. Before randomization tumour of all subjects will be analyzed to detect the KRAS mutational status. Subjects will only be randomized into these two arms if the tumour shows KRAS wild-type. Subjects with KRAS mutant colorectal tumours will receive XELOX alone. Subjects will receive treatment cycles every three weeks. Treatment will continue until subjects are diagnosed with disease progression or intolerable toxicity, at which time the subjects will be withdrawn from the treatment phase. If a subject withdraws from chemotherapy due to toxicity the subjects will be allowed to continue with panitumumab monotherapy with or without one of the chemotherapy components until disease progression. After withdrawing panitumumab and XELOX treatment, all subjects will end the treatment phase and will enter a follow-up phase until 6 months after the last patient stopped treatment (with a safety follow-up visit after 56 days ± 3 days and long term follow-up visits every 12 weeks). During the treatment phase subjects will be evaluated for tumour response every 9 weeks (± one week) through to week 45, and every 12 weeks (± two weeks) thereafter, until disease progression. Subjects with symptoms suggestive of disease progression should be evaluated for tumour response at the time symptoms occur.

  Eligibility

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

Inclusion Criteria:

  • Male or female patients aged 18 years or more, with histologically or cytologically-confirmed and radiologically-measurable metastatic colorectal cancer.
  • One prior chemotherapy regimen for mCRC consisting of first-line fluoropyrimidine and irinotecan based chemotherapy. Subjects must have disease progression (as assessed by the investigator) and must be no candidates for primary metastasectomy.
  • Measurable disease according to RECIST 1.1 guidelines. All sites of disease must have been evaluated within 28 days prior to registration / randomization, and diagnosed by the investigator.
  • Liver and kidney function within defined ranges and sufficient bone marrow reserve.

Exclusion Criteria:

  • Central nervous system metastases, or significant cardiovascular disease.
  • Prior anti-EGFR antibody therapy (e.g. cetuximab) or treatment with small molecule EGFR tyrosine kinase inhibitors (e.g. erlotinib).
  • Prior treatment with oxaliplatin for metastatic disease. Adjuvant therapy with oxaliplatin based combination for non-metastatic disease is allowed if terminated > 6 months prior to initiation of screening and without progression during the treatment with oxaliplatin.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950820

Locations
Germany
AIO-Studien-gGmbH
Berlin, Germany, 10623
Sponsors and Collaborators
AIO-Studien-gGmbH
iOMEDICO AG
Investigators
Principal Investigator: Ralf Grunewald, PD Dr. Gemeinschaftspraxis Hämatologie / Onkologie Im Prüfling 17-19 60389 Frankfurt
  More Information

Additional Information:
No publications provided

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT00950820     History of Changes
Other Study ID Numbers: AIO KRK 0107
Study First Received: July 31, 2009
Last Updated: March 1, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by AIO-Studien-gGmbH:
Open-label
Phase-II-Study
Randomized
Metastatic
Colorectal
Cancer
Panitumumab
Vectibix®
second-line-treatment
KRAS

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
Antibodies, Monoclonal
Fluorouracil
Capecitabine
Oxaliplatin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 19, 2014