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Adenocarcinoma of the ColonPhase 1/2NCT00551421

Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer

A Phase 1/2 study testing pertuzumab, cetuximab and irinotecan hydrochloride in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by National Cancer Institute (NCI) at 1 site in United States.

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

Monoclonal antibodies, such as pertuzumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving pertuzumab together with cetuximab may kill more tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pertuzumab, cetuximab and irinotecan hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
Oct 2007to Jun 2012
Phase
Phase 1/2
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

  • Patients with a history of colorectal cancer (CRC) treated by surgical resection and who develop radiological or clinical evidence of metastatic disease do not require separate histological or cytological confirmation of metastatic disease unless 1 of the following criteria are met:
  • More than 5 years has elapsed between the primary surgery and the development of metastatic disease
  • The primary cancer was stage I
  • Patients must have representative tumor specimens in paraffin blocks or at least 15 unstained slides with an associated pathology report obtained at any time prior to study entry:
  • Cytology specimens are not acceptable replacements
  • Patients must have their tumor tissue screened for KRAS mutation status, and be found to have a KRAS wild-type tumor:
Show all 77Show fewer
  • No KRAS-mutated tumor
  • Locally advanced or metastatic disease
  • Not curable by surgery or amenable to radiotherapy with curative intent
  • Must have received an cetuximab-containing regimen for at least 6 weeks for treatment of metastatic disease
  • Documented progression of disease or intolerable toxicity during or within 3 months of receiving this regimen
  • Patients who have received an cetuximab-containing regimen as adjuvant therapy for resected stage II or III CRC are eligible provided recurrent disease is documented < 6 months after completion of adjuvant treatment
  • Must have received >= 1 prior chemotherapeutic regimen for treatment of metastatic disease with any of the following:
  • Cetuximab
  • Must have resolution of any skin rash related to prior treatment with cetuximab
  • No prior cetuximab which required a dose reduction for toxicity
  • 5-fluorouracil or capecitabine
  • Irinotecan hydrochloride or oxaliplatin
  • Measurable disease by CT scan or physical exam
  • ECOG performance status (PS) 0-1 (Karnofsky PS 70-100%)
  • Life expectancy > 12 weeks
  • Absolute neutrophil count >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Leukocytes >= 3,000/mcL
  • Hemoglobin >= 9 g/dL (transfusion, erythropoietin, or other approved hematopoietic growth factors allowed)
  • Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • AST and ALT =< 5 times ULN
  • Creatinine normal OR Creatinine clearance >= 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to and during study therapy
  • Cardiac left ventricular ejection fraction >= 50% OR >= lower limit of normal
  • No evidence of left ventricular wall motion abnormalities as measured by ECHO or MUGA scan
  • None of the following cardiac conditions:
  • Uncontrolled high blood pressure
  • Unstable angina
  • Symptomatic congestive heart failure
  • Congestive heart failure, cardiac dysfunction, or cardiomyopathy requiring medication treatment
  • Myocardial infarction within the past 6 months
  • Serious uncontrolled cardiac arrhythmia
  • New York Heart Association class III or IV heart disease
  • No active or uncontrolled infection
  • No predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline pattern of > 3 loose stools/day (in patients without a colostomy or ileostomy)
  • Patients with a colostomy or ileostomy may be eligible at investigator discretion
  • No psychiatric illness/social situation that would limit compliance with study requirements
  • No other prior or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of the cervix, lobular carcinoma in situ in one breast, or other cancer from which the patient has been disease-free for at least 5 years
  • No other medical or psychiatric disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the study results or render the patient at high risk for treatment complications
  • No history of allergic reactions, hypersensitivity, or intolerance to cetuximab, and/or compounds of similar chemical or biologic composition to pertuzumab or cetuximab (i.e., other monoclonal antibodies such as bevacizumab) that led to discontinuation of the drug
  • Patients able to tolerate subsequent infusions after a reaction are eligible
  • At least 4 weeks since prior major surgery (e.g., laparotomy) and recovered (Insertion of a vascular access device is not considered major or minor surgery)
  • At least 2 weeks since prior minor surgery and recovered (Insertion of a vascular access device is not considered major or minor surgery)
  • At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy)
  • At least 4 weeks since prior bevacizumab
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • No prior agents directed against EGFR and/or HER2
  • No more than one prior treatment regimen for metastatic disease; Prior chemotherapy in the adjuvant setting following resection of stage II or III disease allowed provided the regimen did not contain irinotecan hydrochloride and/or an agent directed against EGFR and/or HER2
  • No prior doxorubicin or liposomal doxorubicin at doses > 360 mg/m^2; epirubicin at doses > 720 mg/m^2; mitoxantrone at doses > 120 mg/m^2; or idarubicin at doses > 90 mg/m^2
  • No prior radiotherapy to > 15% of the bone marrow
  • No prior standard adjuvant chemoradiotherapy for rectal cancer
  • No phenytoin, phenobarbital, carbamazepine, or any other enzyme-inducing anti-convulsant drugs (EIACDs) for at least 7 days before, during, and for 7 days after the final dose of irinotecan hydrochloride
  • Concurrent gabapentin or other non-EIACDs are allowed
  • No St. John's wort for at least 14 days before, during, and for 7 days after the final dose of irinotecan hydrochloride
  • No concurrent corticosteroids, except for stable doses of prednisone (< 20 mg/day or equivalent), topical or inhaled corticosteroids, or corticosteroids for reasons unrelated to treatment of colorectal cancer
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) for any of the following reasons:
  • To avoid dose reductions or delays
  • Prophylactic treatment
  • Treatment of febrile neutropenia
  • No other concurrent HER family-targeted therapy
  • No concurrent rifampin
  • No concurrent herbal remedies unless initiated prior to study entry
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy, including cytotoxic chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or biological anticancer therapy
  • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
  • Site of the primary lesion must be or have been confirmed endoscopically, radiologically, or surgically to be or have been in the large bowel
  • No known brain metastases
  • No concurrent fluconazole

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase I/II Trial of Pertuzumab in Combination With Cetuximab and Irinotecan in Previously Treated Metastatic Colorectal Cancer

Monoclonal antibodies, such as pertuzumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving pertuzumab together with cetuximab may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of pertuzumab when given together with cetuximab and to see how well they work in treating patients with previously treated locally advanced or metastatic colorectal cancer

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety, tolerability, and recommended phase II dose of pertuzumab when administered in combination with cetuximab in patients with cetuximab-refractory locally advanced or metastatic colorectal cancer.

II. To evaluate the objective tumor response rate (RR) in patients treated with this regimen.

SECONDARY OBJECTIVES:

  1. To evaluate the median progression-free survival (PFS) of patients treated with this regimen.

II. To evaluate the median overall survival (OS) of patients treated with this regimen.

III. To evaluate the RR, PFS, and OS in a subgroup of patients who are EGFR-positive by immunohistochemistry.

IV. To explore the relationship between skin rash and the efficacy outcomes of RR, PFS, and OS in these patients.

  1. To explore the relationship between objective tumor response on positron emission tomography (PET) scan after course two and the efficacy outcomes of RR, PFS, and OS in these patients.

VI. To explore the relationship between a variety of laboratory correlates and the efficacy outcomes of RR, PFS, and OS in these patients.

OUTLINE: This is a multicenter, phase I dose-escalation study of pertuzumab followed by a phase II study.

PHASE I: Patients receive pertuzumab IV over 30-60 minutes on day 1. Patients also receive cetuximab IV over 60-120 minutes on days 2, 8, and 15 of course 1 and on days 1, 8, and 15 in all subsequent courses.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive treatment as in phase I. Pertuzumab is administered at the recommended phase II dose (determined in phase I). Previously collected tumor tissue samples are analyzed for correlative studies. Samples are analyzed for KRAS mutations via polymerase chain reaction and pyrosequencing; EGFR expression via immunohistochemistry and fluorescent in situ hybridization (FISH); HER receptor and ligand gene expression; and circulating tumor cells. Additional blood samples are collected periodically to isolate circulating tumor cells and are analyzed via FISH analysis.

After completion of study treatment, patients are followed at 30 days and then periodically thereafter.

Being tested
pertuzumab, cetuximab, irinotecan hydrochloride, immunohistochemistry staining method, fluorescence in situ hybridization
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

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

  • pertuzumabBiological

    Also called 2C4 antibody, monoclonal antibody 2C4, Perjeta, rhuMAb-2C4

    Given IV

  • cetuximabBiological

    Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225

    Given IV

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

  • immunohistochemistry staining methodOther

    Also called immunohistochemistry

    Correlative study

  • fluorescence in situ hybridizationOther

    Also called fluorescence in situ hybridization (FISH)

    Correlative study

  • gene expression analysisOther

    Correlative study

  • mutation analysisOther

    Correlative study

  • polymerase chain reactionOther

    Also called PCR

    Correlative study

  • laboratory biomarker analysisOther

    Correlative study

Study groups in NCT00551421
Study groupRoleWhat they receive
Arm IExperimentalPhase I: Patients receive pertuzumab IV over 30-60 minutes on day 1. Patients also receive cetuximab IV over 60-120 minutes on days 2, 8, and 15 of course 1 and on days 1, 8, and 15 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Phase II: Patients receive treatment as in phase I. Pertuzumab is administered at the recommended phase II dose (determined in phase I).
Receives: Biological: pertuzumab; Biological: cetuximab; Drug: irinotecan hydrochloride; Other: immunohistochemistry staining method; Other: fluorescence in situ hybridization; Other: gene expression analysis; Other: mutation analysis; Other: polymerase chain reaction; Other: laboratory biomarker analysis

What is being measured

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

  1. Recommended Phase II Dose of Pertuzumab When Administered in Combination With Cetuximab (Phase I)

    The regimen was deemed intolerable so there was no recommended phase II dose.

    Measured: 28 days

  2. Objective Tumor Response Rate Defined as the Proportion of Patients With a Best Overall Response of CR or PR, Per RECIST Criteria (Phase II)

    Objective tumor response rate defined as the proportion of patients with a best overall response of CR or PR, per RECIST criteria (Phase II).

    Measured: Best tumor response from time period of start of study treatment to study discontinuation.

Secondary outcomes (2)

  1. Progression-free Survival

    The duration of time from start of study treatment to time of objective disease progression or death.

    Measured: The duration of time from start of study treatment to time of objective disease progression or death.

  2. Overall Survival

    The duration of time from start of study treatment to death from any cause.

    Measured: The duration of time from start of study treatment to death from any cause.

Timeline

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

  1. First posted31 Oct 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionNov 2010
  4. Study completionJun 2012

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00551421
Sponsor's protocol ID
NCI-2009-00241
Other IDs
07-070, U01CA062490
Status last verified
Jul 2014
First submitted
30 Oct 2007
Last updated
31 Mar 2015
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing pertuzumab, cetuximab and irinotecan hydrochloride in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by National Cancer Institute (NCI) at 1 site in United States.

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 77 inclusion and 0 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 31 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 combined 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.

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 23 Feb 2015). 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?

Recommended Phase II Dose of Pertuzumab When Administered in Combination With Cetuximab (Phase I) (time frame: 28 days). 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 NCT00551421.

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 31 Mar 2015.

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