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Advanced Gastric CancerPhase 2PF299804-AGCNCT01152853

PF-00299804 Monotherapy in Patients With HER-2 Positive Advance Gastric Cancer

A Phase 2 study testing PF00299804 in people with Advanced Gastric Cancer and HER2, run by Seoul National University Hospital at 1 site in South Korea.

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

In case of gastric cancer, the incidence of HER-2 positivity (2+, 3+ on IHC and/or FISH (+)) is reported as similar as that of breast cancer, that is 22% of all cases. A recent ToGA Trial, phase III trial comparing trastuzumab combined with chemotherapy (fluoropyrimidine+cisplatin) versus chemotherapy alone in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Gastric Cancer, HER2
What is being tested?
PF00299804
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteSouth Korea
Study dates
Jul 2010to Sep 2012
Phase
Phase 2
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

  • Age > 18 years
  • A patient who is able to walk and should have ECOG performance status of 0-2.
  • Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy.
  • HER2 positive tumour (primary tumour or metastasis defined as 1) 3+ on IHC and/or 2) FISH (+)
  • Failure to at least one chemotherapy regimen
  • trastuzumab or lapatinib-pretreated patient is eligible
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  • Measurable or non-measurable-evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
  • Adequate bone marrow function, including:
  • Adequate renal function, including:
  • Adequate liver function, including:
  • Adequate Cardiac Function, including:
  • 12-Lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention;
  • QTc interval 470 msec and without history of Torsades de Pointes or other symptomatic QTc abnormality;
  • LVEF (by MUGA or echocardiogram) of ≥50%.
  • Brain metastasis allowed if any necessary treatment has been completed and the patient is radiologically and neurologically stable off corticosteroids at least 2 weeks prior to enrollment
  • A patient with the willingness to comply with the study protocol during the study period and capable of complying with it.
  • A patient who signed the informed consent prior to the participation of the study and who understands that he/she has a right to withdrawal from participation in the study at any time without any disadvantages.

Who cannot join

  • Patients with known active brain metastases or any leptomeningeal metastases;
  • Patients with previously diagnosed brain metastases for which treatment (radiation or surgery) is recommended in judgment of investigator are eligible if they have completed their CNS treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 2 weeks and are neurologically stable.
  • Radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non-target lesions), biological or investigational agents within 2 weeks of baseline disease assessments
  • Any surgery (not including minor procedures) within 4 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures;
  • Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication in tablet form;
  • Current enrollment in another therapeutic clinical trial;
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  • Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
  • Patients with known interstitial lung disease;
  • Uncontrolled or significant cardiovascular disease
  • Prior malignancy: Patients will not be eligible if they have evidence of other malignancy (other than non-melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer with PSA < ULN) within the last 5 years.
  • Organ allogenic transplantation requiring immunosuppressive therapy.
  • A patient who developed uncontrolled serious infection or other uncontrolled serious concomitant diseases.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Seoul National University Hospital

    Seoul, 110-744

Other trials in South Korea

About this study

Official title: A Phase II Open Label Trial of PF-00299804 Monotherapy in Patients With HER-2 Positive Advance Gastric Cancer After Failure of At Least One Prior Chemotherapy Regimen

In case of gastric cancer, the incidence of HER-2 positivity (2+, 3+ on IHC and/or FISH (+)) is reported as similar as that of breast cancer, that is 22% of all cases. A recent ToGA Trial, phase III trial comparing trastuzumab combined with chemotherapy (fluoropyrimidine+cisplatin) versus chemotherapy alone in chemotherapy-naïve HER-2 (+) gastric cancer shows the significant benefit of using trastuzumab in terms of overall survival and progression-free survival. It provides the clinical evidence of HER-2 as a reasonable and potential therapeutic target in gastric cancer.

Nowadays, lapatinib, HER-1 and HER-2 dual inhibitor, is also testing under the clinical trial in gastric cancer.

In preclinical study, PF-00299804 is highly active in HER-2 amplified gastric cancer cell lines.(SNU preclinical data) So, we plan this phase II trial of PF-00299804 monotherapy in patients with HER-2 positive advance gastric cancer after failure of at least one chemotherapy regimen.

Read the detailed description

The role of HER-2 during carcinogenesis and its prognostic role in breast cancer has been already well established. Furthermore the value of HER-2 as a reasonable therapeutic target in breast cancer has translated into the good clinical therapeutic result using HER-2 targeting agent, such as trastuzumab and lapatinib.

In case of gastric cancer, the incidence of HER-2 positivity (2+, 3+ on IHC and/or FISH (+)) is reported as similar as that of breast cancer, that is 22% of all cases. A recent ToGA Trial, phase III trial comparing trastuzumab combined with chemotherapy (fluoropyrimidine+cisplatin) versus chemotherapy alone in chemotherapy-naïve HER-2 (+) gastric cancer shows the significant benefit of using trastuzumab in terms of overall survival and progression-free survival. It provides the clinical evidence of HER-2 as a reasonable and potential therapeutic target in gastric cancer.

Nowadays, lapatinib, HER-1 and HER-2 dual inhibitor, is also testing under the clinical trial in gastric cancer.

PF-00299804 is an orally available, potent, and highly selective irreversible small molecule inhibitor of the Human Epidermal Growth Factor Receptor (HER) family of tyrosine kinases:HER-1 (EGFR), HER-2 and HER-4 (HER-3 does not possess kinase activity). PF-00299804 inhibits the tyrosine kinase activity of the HER family through binding at the ATP binding site, which results in covalent modification of a cystine in the ATP binding pocket. The unique irreversible and highly selective properties of PF-00299804 for the HER kinase family results in sustained suppression of receptor tyrosine kinase activity. The long-lasting inhibition of receptor phosphorylation reduces concern over potentially short plasma half-lives. Furthermore, the low nanomolar potency and irreversible binding of the intended targets reduce the need for high peak plasma levels, which in turn could minimize target-nonspecific toxicities.

In preclinical study, PF-00299804 is highly active in HER-2 amplified gastric cancer cell lines.(SNU preclinical data)

Overall, the standard of care for advanced gastric cancer has been of modest benefit with plateau in response rates using various combination chemotherapies. Therefore, development of treatment options for these advanced gastric cancer patients, especially HER-2 (+) gastric cancer patients, remains a target of active research.

So, the investigators plan this phase II trial of PF-00299804 monotherapy in patients with HER-2 positive advance gastric cancer after failure of at least one chemotherapy regimen.

Being tested
PF00299804
Keywords
advanced gastric cancer, HER2, PF00299804

What participants receive

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

  • PF00299804Drug

    Also called PF-00299804

    PF-00299804 will be given orally once daily at 45 mg daily. Patients will take study drug continuously, with cycles of 28 days.

Study groups in NCT01152853
Study groupRoleWhat they receive
single armExperimentalPF00299804 treatment arm
Receives: Drug: PF00299804

What is being measured

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

  1. progression-free survival at 4-months (PFS4mo)

    PFS is defined as the interval from the date of enrollment to the date of disease progression or death due to any cause, whichever occurs first. PFS4m is defined as the proportion of patients alive and progression-free at 4 months relative to all enrolled patients.

    Measured: 10 months

Secondary outcomes (3)

  1. Overall Response Rate

    Overall Response Rate (BOR) per RECIST Confirmed responses are defined as those that persist on a follow-up imaging assessment 4 weeks after the initial objective documentation of response.

    Measured: 6 months

  2. Overall Survival (OS)

    Overall Survival (OS), defined as the time from enrollment to the date of death due to any cause.

    Measured: 2 years

  3. toxicity

    Overall Safety Profile, as characterized by type, frequency, severity as graded by NCI Common Toxicity Criteria for Adverse Events version 3.0 (NCI CTCAEv3.0), timing and relationship to treatment, and laboratory abnormalities observed.

    Measured: 12 months

Timeline

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

  1. First posted29 Jun 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionJul 2011
  4. Study completionSep 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01152853
Sponsor's protocol ID
H-1004-031-315
Acronym
PF299804-AGC
Status last verified
May 2015
First submitted
20 Jun 2010
Last updated
20 Nov 2015
Results posted
No
Data monitoring committee
No

Publications

  • Oh DY, Lee KW, Cho JY, Kang WK, Im SA, Kim JW, Bang YJ. Phase II trial of dacomitinib in patients with HER2-positive gastric cancer. Gastric Cancer. 2016 Oct;19(4):1095-1103. doi: 10.1007/s10120-015-0567-z. Epub 2015 Nov 18.

    PubMed 26581547

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PF00299804 in people with Advanced Gastric Cancer and HER2, run by Seoul National University Hospital at 1 site in South Korea.

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 17 inclusion and 12 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 20 Nov 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 South Korea. 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 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?

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?

progression-free survival at 4-months (PFS4mo) (time frame: 10 months). 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 NCT01152853, 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 20 Nov 2015.

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