Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01152853
Other study ID # H-1004-031-315
Secondary ID
Status Completed
Phase Phase 2
First received June 20, 2010
Last updated November 17, 2015
Start date July 2010
Est. completion date September 2012

Study information

Verified date May 2015
Source Seoul National University Hospital
Contact n/a
Is FDA regulated No
Health authority Republic of Korea: Food and Drug Administration
Study type Interventional

Clinical 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 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 28
Est. completion date September 2012
Est. primary completion date July 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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:

1. 12-Lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention;

2. QTc interval 470 msec and without history of Torsades de Pointes or other symptomatic QTc abnormality;

3. 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.

Exclusion Criteria:

- 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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
PF00299804
PF-00299804 will be given orally once daily at 45 mg daily. Patients will take study drug continuously, with cycles of 28 days.

Locations

Country Name City State
Korea, Republic of Seoul National University Hospital Seoul

Sponsors (2)

Lead Sponsor Collaborator
Seoul National University Hospital Pfizer

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 No
Secondary 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. 6 months No
Secondary Overall Survival (OS) Overall Survival (OS), defined as the time from enrollment to the date of death due to any cause. 2 years No
Secondary 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. 12 months Yes
See also
  Status Clinical Trial Phase
Recruiting NCT05028933 - IMC001 for Clinical Research on Advanced Digestive System Malignancies Phase 1
Completed NCT00821990 - Second-line Therapy Versus Supportive Care for Pretreated Advanced Gastric Cancer Phase 3
Recruiting NCT04385641 - Study on the Safety and Effectiveness of UCB-NK Cell Infusion in the Treatment of Advanced Gastric Cancer and Gastroesophageal Cancer N/A
Completed NCT01248403 - A Randomized, Double Blind Study Evaluating Paclitaxel With and Without RAD001 in Patients With Gastric Carcinoma After Prior Chemotherapy Phase 3
Not yet recruiting NCT01206218 - Evaluation of Customized Treatment According to BRCA1 Assessment in Patients With Advanced Gastric Cancer Phase 2/Phase 3
Completed NCT01851941 - A Phase II Trial of Perioperative Chemotherapy With Oxaliplatin, 5-Fluorouracil, Leucovorin(MODIFIED FOLFOX6) in Patients With Locally Advanced Operable Gastric Cancer Phase 2
Completed NCT00976768 - Biweekly FOLFIRI in Advanced Gastric Cancer (AGC) With Failure of Prior Taxane, Fluoropyrimidine, and Cisplatin Phase 2
Active, not recruiting NCT03223376 - A Phase III Study of Fruquintinib in Combination With Paclitaxel in Second Line Gastric Cancer(FRUTIGA) Phase 3
Completed NCT03609359 - Lenvatinib and Pembrolizumab Simultaneous Combination Study Phase 2
Completed NCT03350477 - Bioinformation Therapy for Gastric Cancer Phase 2/Phase 3
Completed NCT02935634 - A Study to Test Combination Treatments in Participants With Advanced Gastric Cancer Phase 2
Active, not recruiting NCT03579784 - Biomarker-oriented Study of Durvalumab (MEDI4736) in Combination With Olaparib and Paclitaxel in Gastric Cancer Phase 2
Completed NCT02952729 - Study of Antibody Drug Conjugate in Patients With Advanced Breast Cancer Expressing HER2 Phase 1
Recruiting NCT02072317 - Paclitaxel Plus Raltitrexed Plug Compare With Taxol Second-line Treatment for Advanced Gastric Cancer Phase 2
Completed NCT01472250 - A Prospective and Observational Cohort Study to Evaluate the Treatment Model and Medical Economics of Advanced Gastric Cancer Chemotherapy in Clinical Practice in China N/A
Terminated NCT01402401 - Phase II of AUY922 in Second-line Gastric Cancer in Combination With Trastuzumab in HER2 Positive Patients Phase 2
Completed NCT01503372 - FLO +/- Pazopanib as First-line Treatment in Advanced Gastric Cancer Phase 2
Recruiting NCT01015339 - Paclitaxel Plus Capecitabine With Capecitabine Maintenance Treatment in Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction Phase 3
Completed NCT01238055 - Sunitinib + Docetaxel as Second-line Treatment in Gastric Cancer Phase 2
Completed NCT01441336 - Laparoscopic Gastrectomy for Advanced Gastric Cancer Phase 2