Metastatic Colorectal CancerPhase 2NCT00891930
Study to Evaluate Mechanisms of Acquired Resistance to Panitumumab
A Phase 2 study testing Panitumumab, Ganitumab and Irinotecan in people with Metastatic Colorectal Cancer, run by NantBioScience, Inc..
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Panitumumab, Ganitumab and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- No sites listed yet
- Study dates
- 5 May 2009to 22 Jul 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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
Who cannot join
- 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;
Show all 20Show fewer
- 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;
- 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
About this study
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
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.
Read the detailed description
In Part 1, all participants will undergo a baseline tumor biopsy and will receive panitumumab with irinotecan. Participants who respond or have stable disease will continue to receive treatment until radiographically-confirmed disease progression. These participants will then undergo a second tumor biopsy and blood sampling and then proceed to Part 2 of the study. Participants with radiographically confirmed disease progression at the time of the first tumor measurement will undergo blood sampling and proceed directly to Part 2.
In Part 2, participants will receive panitumumab with ganitumab. In both parts of the study, panitumumab and irinotecan (Part 1) and panitumumab and ganitumab (Part 2) will be administered every 2 weeks until disease progression, intolerability, withdrawal of consent, death, or unless otherwise indicated by the study team.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Panitumumab, Ganitumab, Irinotecan
- Keywords
- wild-type KRAS, panitumumab, biomarker, mechanisms of acquired resistance, metastatic colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabBiological
Also called Vectibix
Panitumumab 6 mg/kg administered via IV infusion over 60 minutes
GanitumabBiological
Also called AMG 479
AMG 479 12 mg/kg adminstered by IV infusion over 60 minutes
IrinotecanDrug
Irinotecan starting dose of 180 mg/m² adminstered via IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Panitumumab; Biological: Ganitumab; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.
Measured: from first dose of investigational product up to 152 weeks
Progression-Free Survival for Part 1
Time from the first dose of investigational product to the first date of disease progression per the modified RECIST v1.0 or death by any cause, initiating a new line of antitumor therapy, or receiving study treatment in Part 2, whichever is earlier in Part 1. Disease progression is a >= 20% increase in the sum of the longest diameter of the target lesions as compared to the smallest sum while on study per RECIST v1.0
Measured: from first dose of investigational product up to 152 weeks
Progression-Free Survival for Part 2
Time from the start of Part 2 to the first date of disease progression per the modified RECIST v1.0 or death by any cause, initiating a new line of antitumor therapy, or receiving study treatment in Part 2, whichever is earlier. Disease progression is a >= 20% increase in the sum of the longest diameter of the target lesions as compared to the smallest sum while on study per RECIST v1.0.
Measured: 119 weeks from the start of part 2, up to a maximum duration of 152 week
Overall Survival for Part 1
Time from the first dose of investigational product to death from any cause in Part 1.
Measured: from first dose of investigational product up to 152 weeks
Overall Survival for Part 2
Time from the start of Part 2 to death from any cause.
Measured: from the start of Part 2 up to 119 weeks
Time to Response for Part 1
Time from the first dose of investigational product to the date of first confirmed objective response in Part 1. An objective response is defined as a confirmed complete response or partial response per modified RECIST v1.0 criteria during the treatment period. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.
Measured: from first dose of investigational product up to 152 weeks
Duration of Response for Part 1
Time from first confirmed objective response to disease progression per modified RECIST v1.0 in Part 1. An objective response is defined as a confirmed complete response or partial response per modified RECIST v1.0 criteria during the treatment period. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR; Disease progression is a >= 20% increase in the sum of the longest diameter of the target lesions as compared to the smallest sum while on study.
Measured: from first dose of investigational product up to 152 weeks
Part 2 Time to Response and Duration of Response
Time to response was defined as the time from study day 1 to the first observation of an objective response (confirmed complete response or partial response using modified Response Evaluation Criteria in Solid Tumors [RECIST]). Duration of response was the time from the first observation of an objective response to the subsequent time of disease progression (per modified RECIST or clinical progression, whichever came first) or death due to any cause. Objective response = a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors [RECIST]. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From time of randomization until confirmed complete response or partial response (part 2: up to 119 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2009 (estimated)
- Study start5 May 2009
- Primary completion22 Jul 2013
- Study completion22 Jul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- NantBioScience, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00891930
- Sponsor's protocol ID
- 20070820
- Other IDs
- 2008-004752-77, 2008
- Status last verified
- Jun 2024
- First submitted
- 12 Mar 2009
- Last updated
- 17 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28945848
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00891930
- Acronym / sponsor ID
- 20070820
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- wild-type KRAS, panitumumab, biomarker, mechanisms of acquired resistance, metastatic colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- NantBioScience, Inc.Industry (pharma, biotech, devices)
- Study start
- 5 May 2009 (actual)
- Primary completion
- 22 Jul 2013 (actual)
- Study completion
- 22 Jul 2013 (actual)
- First posted
- 1 May 2009 (estimated)
- Results
- Posted 8 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In Part 1, all participants will undergo a baseline tumor biopsy and will receive panitumumab with irinotecan. Participants who respond or have stable disease will continue to receive treatment until radiographically-confirmed disease progression. These participants will then undergo a second tumor biopsy and blood sampling and then proceed to Part 2 of the study. Participants with radiographically confirmed disease progression at the time of the first tumor measurement will undergo blood sampling and proceed directly to Part 2.
In Part 2, participants will receive panitumumab with ganitumab. In both parts of the study, panitumumab and irinotecan (Part 1) and panitumumab and ganitumab (Part 2) will be administered every 2 weeks until disease progression, intolerability, withdrawal of consent, death, or unless otherwise indicated by the study team.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Panitumumab | Experimental | Biological: Panitumumab, Biological: Ganitumab, Drug: IrinotecanParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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;
Key exclusion criteria (20 listed)
- History of other primary cancer, unless:
- Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease,
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanitumumabAlso: VectibixPanitumumab 6 mg/kg administered via IV infusion over 60 minutes | Biological | Panitumumab |
| GanitumabAlso: AMG 479AMG 479 12 mg/kg adminstered by IV infusion over 60 minutes | Biological | Panitumumab |
| IrinotecanIrinotecan starting dose of 180 mg/m² adminstered via IV infusion | Drug | Panitumumab |
Primary outcome
PFS Hazard Ratio
Time frame: From baseline up to 152 weeks (from baseline to the time of the second biopsy prior to entering part 2) .
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
Objective Response Rate in Part 2
Time frame: From time of randomization until confirmed complete response or partial response (part 2: up to 119 weeks)
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.
8 secondary outcomes
Objective Response Rate for Part 1
Time frame: from first dose of investigational product up to 152 weeks
Progression-Free Survival for Part 1
Time frame: from first dose of investigational product up to 152 weeks
Progression-Free Survival for Part 2
Time frame: 119 weeks from the start of part 2, up to a maximum duration of 152 week
Overall Survival for Part 1
Time frame: from first dose of investigational product up to 152 weeks
Overall Survival for Part 2
Time frame: from the start of Part 2 up to 119 weeks
Time to Response for Part 1
Time frame: from first dose of investigational product up to 152 weeks
Duration of Response for Part 1
Time frame: from first dose of investigational product up to 152 weeks
Part 2 Time to Response and Duration of Response
Time frame: From time of randomization until confirmed complete response or partial response (part 2: up to 119 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28945848Siena 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panitumumab, Ganitumab and Irinotecan in people with Metastatic Colorectal Cancer, run by NantBioScience, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS Hazard Ratio (time frame: From baseline up to 152 weeks (from baseline to the time of the second biopsy prior to entering part 2) .). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00891930, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2024.