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Rectal CancerPhase 1NCT00101894

Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer

A Phase 1 study testing FOLFOX-4, AMG 706 and Panitumumab (Part 1a only) in people with Rectal Cancer and Colon Cancer, run by Amgen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to characterize the safety and tolerability of AMG 706 plus panitumumab when administered with either FOLFIRI or FOLFOX4 chemotherapy regimens. This is a Phase 1b clinical study. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rectal Cancer, Colon Cancer
What is being tested?
FOLFOX-4, AMG 706 and Panitumumab (Part 1a only)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
No sites listed yet
Study dates
Dec 2004to Dec 2011
Phase
Phase 1
Are there results?
None posted in the registry

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

None listed.

Who cannot join

  • More than 1 prior chemotherapy regimen for metastatic CRC
  • Central nervous system (CNS) metastases
  • History of venous thrombosis
  • Myocardial infarction, cerebrovascular accident, transient ischemic attack, grade 2 or greater peripheral vascular disease, congestive heart failure, ongoing arrhythmias requiring medication, or unstable angina within 1 year before study enrollment
  • History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan
  • Average systolic blood pressure > 150mm Hg or average diastolic blood pressure of > 90mm Hg
Show all 16Show fewer
  • Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions
  • Prior AMG 706, oral inhibitors of AMG706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab [Erbitux®] or EMD 72000)
  • Systemic chemotherapy within 28 days before study enrollment
  • Major surgery within 28 days or minor surgery within 7days of study enrollment
  • History of life threatening ventricular arrhythmia (eg, sustained ventricular tachycardia)
  • Female and male subjects of childbearing potential not using adequate contraceptive precautions
  • Participation in therapeutic clinical trials within 30 days before study enrollment
  • Not recovered from all previous therapies
  • Clinically significant open would, ulcer or fracture
  • Any co-morbid medical condition that would increase the risk of toxicity

About this study

Official title: An Open-Label, Dose-Finding Study to Evaluate the Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer

The purpose of this study is to characterize the safety and tolerability of AMG 706 plus panitumumab when administered with either FOLFIRI or FOLFOX4 chemotherapy regimens. This is a Phase 1b clinical study.

Being tested
FOLFOX-4, AMG 706, Panitumumab (Part 1a only), FOLFIRI
Keywords
AMG 706, Panitumumab
Medical subject headings
Rectal Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFOX-4Drug

    The FOLFOX-4 regimen will be administered every 2 weeks as follows:

    Day 1: oxaliplatin (ELOXATIN™) 85 mg/m2 IV infusion and leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion given over 120 ± 10 minutes at the same time in separate bags using a Y-line, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed by 5-FU 600 mg/m2 IV infusion as a 22-hour ± 2 hours continuous infusion Day 2: leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion over 120 ± 10 minutes, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed

  • AMG 706Drug

    AMG 706 is a small organic molecule that has been shown in preclinical pharmacology studies to be a potent, oral, multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively inhibiting all known VEGF receptors, PDGF receptor, and Kit.

  • Panitumumab (Part 1a only)Biological

    Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.

  • FOLFIRIDrug

    Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-week cycle. Leucovorin will be administered over 2 hours ± 15 minutes during the irinotecan infusion but without mixing, immediately followed by a 5-FU bolus and a 5-FU 46-hour ± 2-hour continuous intravenous infusion.

Study groups in NCT00101894
Study groupRoleWhat they receive
Part 2 AMG 706 (MTD) + FOLFOX-4ExperimentalMaximum Tolerated Dose of AMG 706 established in Part 1b + FOLFOX-4
Receives: Drug: FOLFOX-4; Drug: AMG 706
125 mg QD AMG 706 + FOLFOX-4Experimental125 mg QD AMG 706 + FOLFOX-4
Receives: Drug: FOLFOX-4; Drug: AMG 706
50 mg QD AMG706 + panitumumab + FOLFIRIExperimental50 mg QD AMG706 + panitumumab + FOLFIRI
Receives: Drug: AMG 706; Biological: Panitumumab (Part 1a only); Drug: FOLFIRI
Part 2 AMG 706 (MTD) + FOLFIRIExperimentalMaximum Tolerated Dose of AMG 706 established in Part 1b + FOLFIRI
Receives: Drug: AMG 706; Drug: FOLFIRI
100 mg QD AMG 706 + FOLFIRIExperimental100 mg AMG 706 + FOLFIRI
Receives: Drug: AMG 706; Drug: FOLFIRI
75 mg QD AMG 706 + panitumumab + FOLFOX-4Experimental75 mg QD AMG 706 + panitumumab + FOLFOX-4
Receives: Drug: FOLFOX-4; Drug: AMG 706; Biological: Panitumumab (Part 1a only)
75 mg BID AMG 706 + panitumumab + FOLFIRIExperimental75 mg BID AMG 706 + panitumumab + FOLFIRI
Receives: Drug: AMG 706; Biological: Panitumumab (Part 1a only); Drug: FOLFIRI
125 mg QD AMG 706 + panitumumab + FOLFIRIExperimental125 mg QD AMG 706 + panitumumab + FOLFIRI
Receives: Drug: AMG 706; Biological: Panitumumab (Part 1a only); Drug: FOLFIRI
125 mg QD AMG 706 + FOLFIRIExperimental125 mg QD AMG 706 + FOLFIRI
Receives: Drug: AMG 706; Drug: FOLFIRI
100 mg QD AMG 706 + panitumumab + FOLFIRIExperimental100 mg QD AMG 706 + panitumumab + FOLFIRI
Receives: Drug: AMG 706; Biological: Panitumumab (Part 1a only); Drug: FOLFIRI
75 mg QD AMG 706 + FOLFOX-4Experimental75 mg QD AMG 706 + FOLFOX-4
Receives: Drug: FOLFOX-4; Drug: AMG 706
100 mg QD AMG 706 + FOLFOX-4Experimental100 mg QD AMG 706 + FOLFOX-4
Receives: Drug: FOLFOX-4; Drug: AMG 706
50 mg QD AMG 706 + panitumumab + FOLFOX-4Experimental50 mg QD AMG 706 + panitumumab + FOLFOX-4
Receives: Drug: FOLFOX-4; Drug: AMG 706; Biological: Panitumumab (Part 1a only)
75 mg QD AMG706 + panitumumab + FOLFIRIExperimental75 mg QD AMG706 + panitumumab + FOLFIRI
Receives: Drug: AMG 706; Biological: Panitumumab (Part 1a only); Drug: FOLFIRI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities

    Measured: First 2 cycles

  2. Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities

    Measured: First 2 cycles

  3. Part 2 - The overall objective tumor response rate (complete and partial response) in subjects treated with AMG 706 (at the dose determined in Part 1b), with either the FOLFIRI or FOLFOX-4 chemotherapy regimen

    Measured: Every 8 weeks (+/- 7 days)

Secondary outcomes (23)

  1. Part 1a - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with panitumumab and AMG 706

    Measured: Cycle 1 and 2 (Days 1, 2, 3)

  2. Part 1a - The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with panitumumab and AMG 706

    Measured: Cycle 1 and 2 (Day 1)

  3. Part 1a - The objective tumor response rate (complete and partial response) throughout the study

    Measured: Every 6 to 8 weeks

  4. Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities

    Measured: Every visit

  5. Part 1b - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen

    Measured: Cycle 2 (Day 1-2), Cycle 3 (Day 1)

  6. Part 1b - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with AMG 706

    Measured: Cycle 1 and 2 (Day 3)

  7. Part 2 - Duration of response: (Calculated for only those subjects who respond)

    Measured: Time from first objective tumor response (subsequently confirmed at least 4 weeks later) to objective disease progression or death.

  8. Part 2 - Time-to-progression

    Measured: Time from first dose of investigational product to objective disease progression or death due to disease progression.

  9. Part 1b - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with AMG 706

    Measured: Cycle 1 and 2 (Days 1, 2, 3)

  10. Part 1b- The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with AMG 706

    Measured: Cycle 1 and 2 (Day 1)

  11. Part 1b - The objective tumor response rate (complete and partial response) throughout the study

    Measured: Every 8 weeks (+/- 7 days)

  12. Part 2 - Overall survival

    Measured: Time from first dose of investigational product to death. Subjects who have not died while on study or are lost to follow-up will be censored at their last contact date. (Time on study plus 36 months of long term follow-up)

  13. Part 2 - The incidence of adverse events and clinical laboratory abnormalities

    Measured: Every visit

  14. Part 2 - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen (at a subset of the study centers with the capabilities to draw, ship and process PK samples)

    Measured: Cycles 2, 4, 7, and every 3 subsequent cycles (Day 1)

  15. Exploratory - Potential biomarker development based on assessment of blood cells, tumor cells, and urine and the proposed mechanism of action of study drugs, and response

    Measured: Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment

  16. Exploratory - The effects of genetic variation in drug metabolism genes, cancer genes, and drug target genes on subject response to investigational products (separate informed consent)

    Measured: Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment

  17. Part 2 - Progression-free survival time

    Measured: Time from first dose of investigational product to objective disease progression or death, subjects who have not progressed or died while on study will be censored at their last evaluable assessment date.

  18. Part 2 - Incidence of subjects undergoing resection of metastases for curative intent

    Measured: As needed

  19. Part 1a - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities

    Measured: Every visit

  20. Part 1a - The PK of AMG 706 when administered with panitumumab and either the FOLFIRI or FOLFOX-4 chemotherapy regimen

    Measured: Cycle 2 (Day 1-2), Cycle 3 (Day 1)

  21. Part 1a - The serum concentration of panitumumab when administered with AMG 706 and either the FOLFIRI or FOLFOX-4 chemotherapy regimen

    Measured: Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 4 (Day 1)

  22. Part 1a - The incidence of HAPA response following panitumumab administration

    Measured: Cycle 1 (Day 1), Cycle 4 (Day 1), End of Study

  23. Part 1a - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with panitumumab and AMG 706

    Measured: Cycle 1 and 2 (Day 3)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2005 (estimated)
  2. Study startDec 2004
  3. Primary completionApr 2010
  4. Study completionDec 2011

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00101894
Sponsor's protocol ID
20040205
Status last verified
Sep 2012
First submitted
18 Jan 2005
Last updated
17 Sep 2012
Results posted
No
Data monitoring committee
No

Publications

  • Tebbutt N, Kotasek D, Burris HA, Schwartzberg LS, Hurwitz H, Stephenson J, Warner DJ, Chen L, Hsu CP, Goldstein D. Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol. 2015 May;75(5):993-1004. doi: 10.1007/s00280-015-2694-y. Epub 2015 Mar 15.

    PubMed 25772756

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing FOLFOX-4, AMG 706 and Panitumumab (Part 1a only) in people with Rectal Cancer and Colon Cancer, run by Amgen.

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 0 inclusion and 16 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 Sep 2012. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities (time frame: First 2 cycles). The study lists 3 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 NCT00101894, 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 Sep 2012.

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