Study to Evaluate Mechanisms of Acquired Resistance to Panitumumab

NCT00891930 | Completed Phase 2 Results

• 2 other identifiers: 200708202008-004752-77
• Study Type: interventional
• Target: 74
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is designed to evaluate the mechanism(s) of resistance to the anti-epidermal growth factor receptor (EGFR) antibody panitumumab given in combination with irinotecan in metastatic colorectal carcinoma (mCRC) patients with wild-type Kirsten rat sarcoma-2 virus oncogene (KRAS) tumor status at the time of initial diagnosis.

Conditions

Metastatic Colorectal Cancer

Keywords

wild-type KRAS; panitumumab; biomarker; mechanisms of acquired resistance; metastatic colorectal cancer

Outcome Measures

Primary Outcomes (2)

• PFS Hazard Ratio

  KRAS mutation status changed from wild-type at baseline to mutant at time of second biopsy in part 1, as measured by the PFS hazard ratio. Hazard ratio is presented as wild-type: mutant

  From baseline up to 152 weeks (from baseline to the time of the second biopsy prior to entering part 2) .

• Objective Response Rate in Part 2

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  From time of randomization until confirmed complete response or partial response (part 2: up to 119 weeks)

Secondary Outcomes (8)

• Objective Response Rate for Part 1

  from first dose of investigational product up to 152 weeks

• Progression-Free Survival for Part 1

  from first dose of investigational product up to 152 weeks

• Progression-Free Survival for Part 2

  119 weeks from the start of part 2, up to a maximum duration of 152 week

• Overall Survival for Part 1

  from first dose of investigational product up to 152 weeks

• Overall Survival for Part 2

  from the start of Part 2 up to 119 weeks

Study Arms (1)

Panitumumab

EXPERIMENTAL

Participants received panitumumab (6 mg/kg starting dose) with irinotecan (starting dose of 180 mg/m²) every 2 weeks (Q2W) during Part 1. Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.

Biological: Panitumumab; Biological: Ganitumab; Drug: Irinotecan

Interventions

Panitumumab BIOLOGICAL

Panitumumab 6 mg/kg administered via IV infusion over 60 minutes

Also known as: Vectibix

Panitumumab

Ganitumab BIOLOGICAL

AMG 479 12 mg/kg adminstered by IV infusion over 60 minutes

Also known as: AMG 479

Panitumumab

Irinotecan DRUG

Irinotecan starting dose of 180 mg/m² adminstered via IV infusion

Panitumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤ 6 months 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 computed tomography (CT) or magnetic resonance imaging (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;
• 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

You may not qualify if:

• 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 CT scan;

Sponsors & Collaborators

• NantBioScience, Inc.: lead

Related Publications (1)

• Siena S, Sartore-Bianchi A, Garcia-Carbonero R, Karthaus M, Smith D, Tabernero J, Van Cutsem E, Guan X, Boedigheimer M, Ang A, Twomey B, Bach BA, Jung AS, Bardelli A. Dynamic molecular analysis and clinical correlates of tumor evolution within a phase II trial of panitumumab-based therapy in metastatic colorectal cancer. Ann Oncol. 2018 Jan 1;29(1):119-126. doi: 10.1093/annonc/mdx504.

  PMID: 28945848 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; ganitumab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Officer
• Organization: ImmunityBio

Bobby.Reddy@Immunitybio.com

866-572-6436

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2009
• First Posted: May 1, 2009
• Study Start: May 5, 2009
• Primary Completion: July 22, 2013
• Study Completion: July 22, 2013
• Last Updated: July 17, 2024
• Results First Posted: February 8, 2016

Record last verified: 2024-06