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

NCT01152853 | Completed Phase 2

• 1 other identifier: H-1004-031-315
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Advanced Gastric Cancer; HER2

Keywords

advanced gastric cancer; HER2; PF00299804

Outcome Measures

Primary Outcomes (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.

  10 months

Secondary Outcomes (3)

• Overall Response Rate

  6 months

• Overall Survival (OS)

  2 years

• toxicity

  12 months

Study Arms (1)

single arm

EXPERIMENTAL

PF00299804 treatment arm

Drug: PF00299804

Interventions

PF00299804 DRUG

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

Also known as: PF-00299804

single arm

Eligibility Criteria

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

You may qualify if:

• 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
• 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:
• 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

You may not qualify if:

• Patients with known active brain metastases or any leptomeningeal metastases;
• a. 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;
• 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.

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Pfizer: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Related Publications (1)

• 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.

  PMID: 26581547 DERIVED

MeSH Terms

Interventions

dacomitinib

Study Officials

• Yung-Jue Bang, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 20, 2010
• First Posted: June 29, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: September 1, 2012
• Last Updated: November 20, 2015

Record last verified: 2015-05

Locations

KR (1)