Phase II Trial of EP4 Receptor Antagonist, AAT-007 (RQ-07; CJ-023,423) in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase II trial of (RQ-07) in advanced solid tumors in prostate, breast or non-small cell lung cancer.

Detailed Description
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This is a phase II trial of (RQ-07) in advanced solid tumors in advanced prostate, breast or lung cancer. The purpose of this trial is to determine whether the administration of the study drug RQ-07 can decrease circulating tumor cells in advanced prostate, breast or lung cancer. Additionally, the study will evaluate whether the study drug may improve outcome in advanced prostate, breast or lungs cancer either by itself or when combined with gemcitabine, a standard chemotherapy drug. The combination of with gemcitabine will only be investigated after disease has worsened with the study drug RQ-07 by itself and only in patients with prostate or lung cancer.

Official Title
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15xxGCC: PHASE II TRIAL OF THE EP4 RECEPTOR ANTAGONIST, AAT-007 (RQ-07; CJ-023,423) IN ADVANCED SOLID TUMORS

Conditions
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Prostate Cancer, Non-Small Cell Lung Cancer, Breast Cancer

Intervention / Treatment
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* Drug: RQ-00000007
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed breast, prostate or non-small cell lung cancer or other A tissue block, 10 unstained slides or fresh tissue biopsy is required. At least 2 weeks should have elapsed since the last treatment and patients should have recovered from previous significant toxicity (i.e. to grade 1 or less). ECOG Performance Status <2. Patient at least 18 years of age or older. Adequate hematological function as defined by the protocol, section 4.1.5. Patients must have a serum creatinine within normal limits, or an estimated or measured creatinine clearance > 35 mg/ml/min. Normal serum electrolytes (no >grade 2 abnormalities), magnesium and phosphorus on the day of therapy. Correction of abnormalities is permitted. Adequate hepatic function per institutional standards (see exclusion). All patients must be informed of the investigational nature of this study and must sign and give written informed consent. Serum calcium, magnesium and potassium must be within normal limits. Supplementation to achieve normal values is permitted. Patients who are potentially fertile and sexually active must be willing to utilize effective birth control. Patients with CNS metastases which are/were symptomatic must have completed therapy (surgery, gamma knife, XRT) and be neurologically stable. Patients must have > or = 4 circulating tumor cells Exclusion Criteria: Patients must not have serious infection or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment. Current uncontrolled cardiac disease Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 4 weeks of registration. Patients with acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition or patients known to be HIV positive Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RQ-00000007 Alone<br>RQ-0000007 250 mg will be self-administered orally, with or without food, each morning and evening, approximately 12 hours apart. | Drug: RQ-00000007<br>* RQ-07 250 mg will taken orally, with or without food, each morning and evening, approximately 12 hours apart. Drug administration will be continuous. Every 21 day period will be considered one cycle of treatment.<br>* Other names: CJ-023,423;|
| Active Comparator: Gemcitabine<br>For patients with breast or lung cancer who have not previously received gemcitabine as part of their therapy or who may benefit from re-challenge with gemcitabine, gemcitabine will be given as an IV. | Drug: RQ-00000007<br>* RQ-07 250 mg will taken orally, with or without food, each morning and evening, approximately 12 hours apart. Drug administration will be continuous. Every 21 day period will be considered one cycle of treatment.<br>* Other names: CJ-023,423;Drug: Gemcitabine<br>* For patients with breast or lung cancer who have not previously received gemcitabine as part of their therapy or who may benefit from re-challenge with gemcitabine, gemcitabine will be administered at 1000 mg/m2 IV over 30 minutes for 3 out of 4 weeks after appropriate pre-medications. Every 4 week period (28 days) will be considered one cycle.<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating Tumor Cells (CTC) | The efficacy of the treatment drug will be assessed by the reduction of the number of CTCs. Blood sample collection will be done to assess CTCs. | Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myeloid Derived Suppressor Cell (MDSC) | The efficacy of the treatment drug RQ-07 will be assessed as a single agent and in combination with gemcitabine in breast cancer and lung cancer patients only. MDSC evaluation will be done via a blood sample collection | Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Disease Progression, Non-Responsive Disease, Advanced Disease