Study of CGC-11047 When Used in Individual Combinations With 1) Gemcitabine or 2) Docetaxel or 3) Bevacizumab or 4) Erlotinib or 5) Cisplatin or 6) 5-Flurouracil or 7) Sunitinib in Patients With Advanced Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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This study will aims to determine the maximum tolerated dose of CGC-11047 when used in individual combinations with gemcitabine, or docetaxel, or bevacizumab, or erlotinib or cisplatin or 5-flurouracil or sunitinib in one of 7 treatment arms. The dose of CGC-11047 will be escalated until the maximum tolerated dose is established.

Detailed Description
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This study will use a dose escalation design to determine the MTD of CGC-11047 when used in individual combinations with gemcitabine, or docetaxel, or bevacizumab, or erlotinib or cisplatin or 5-flurouracil or sunitinib in one of 7 treatment arms. The dose of CGC-11047 will be escalated in cohorts of 3 patients and dose escalation can proceed in each treatment group independent of dose escalation in the other treatment groups. CGC-11047 will be administered IV over 60 minutes and the doses of gemcitabine, docetaxel, bevacizumab, cisplatin, 5-flurouracil or sunitinib will remain fixed according to their respective product labeling.

Official Title
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A Phase I Open Label, Multicenter, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Dose Limiting Toxicity, Safety and Pharmacokinetics of CGC-11047 When Used in Individual Combinations With 1) Gemcitabine or 2) Docetaxel or 3) Bevacizumab or 4) Erlotinib or 5) Cisplatin or 6) 5-Flurouracil or 7) Sunitinib in Patients With Advanced Solid Tumors or Lymphoma

Conditions
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Cancer

Intervention / Treatment
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* Drug: CGC-11047 and gemcitabine
* Drug: CGC-11047 and docetaxel
* Drug: CGC-11047 and bevacizumab
* Drug: CGC-11047 and erlotinib
* Drug: CGC-11047 and cisplatin
* Drug: CGC-11047 and 5-flurouracil / leucovorin
* Drug: CGC-11047 and sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: non-hematological advanced solid tumor malignancy or lymphoma where no curative therapy exists in which monotherapy with gemcitabine or docetaxel or bevacizumab or erlotinib or cisplatin, or 5-flurouracil or sunitinib would otherwise be warranted. measurable disease based on radiographic evaluation or elevated tumor markers. ECOG - 0 or 1 (KPS >70). Life expectancy > 3 months. Exclusion Criteria: chemotherapy within 21 days or radiotherapy within 4 weeks prior to entering the study known active brain metastases or leptomeningeal carcinomatosis. history of a myocardial infarction within the prior 6 months or, hospitalizations for congestive heart failure within the prior 6 months, or active treatment for uncontrolled cardiac arrhythmias clinically significant gastrointestinal tract hemorrhage, requiring transfusion therapy, within the prior 3 months.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CGC-11047 in combination with Gemcitabine | Drug: CGC-11047 and gemcitabine<br>* Gemcitabine: (Closed to enrollment) 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle. CGC-11047 will only be given on days 1 and 15 of each cycle and will start at dose level -1 (50 mg).<br>* Other names: Gemzar;|
| Experimental: 2<br>CGC-11047 in combination with Docetaxel | Drug: CGC-11047 and docetaxel<br>* Docetaxel: (Closed to enrollment) 75 mg/m2 administered IV over 60 minutes every 21 days. CGC-11047 will be administered only on Day 1 of each 21-day cycle and will start at dose level -1 (50 mg).<br>* Other names: Taxotere;|
| Experimental: 3<br>CGC-11047 in combination with Bevacizumab | Drug: CGC-11047 and bevacizumab<br>* Bevacizumab: 5 mg/kg administered IV once every 14 days. CGC-11047 will be administered on Days 1, 8 and 15 of a 28 day cycle.<br>* Other names: Avastin;|
| Experimental: 4<br>CGC-11047 in combination with Erlotinib | Drug: CGC-11047 and erlotinib<br>* Erlotinib: 150 mg taken orally every day of each 28-day cycle. CGC-11047 will be administered on Days 1, 8 and 15 of a 28 day cycle.<br>* Other names: Tarceva;|
| Experimental: 5<br>Cisplatin: 80 mg/m2 administered IV over 1 hour once every 28 days. CGC-11047 will be administered on Days 1, 8 and 15 of a 28 day cycle. | Drug: CGC-11047 and cisplatin<br>* Cisplatin: 80 mg/m2 administered IV over 1 hour once every 28 days. CGC-11047 will be administered on Days 1, 8 and 15 of a 28 day cycle.<br>|
| Experimental: 6<br>CGC-11047 in combination with 5-Flurouracil / Leucovorin | Drug: CGC-11047 and 5-flurouracil / leucovorin<br>* 5-Flurouracil / Leucovorin: Leucovorin 500 mg/m2 IV over 2 hours with 5 - FU 500 mg/m2 IV bolus starting 1 hour into leucovorin infusion weekly for 6 wks, repeated every 56 days. CGC-11047 will be administered on Days 1, 8 and 15 of a 28 day cycle.<br>* Other names: Efudix;|
| Experimental: 7<br>CGC-11047 in combination with Sunitinib | Drug: CGC-11047 and sunitinib<br>* Sunitinib: 50 mg orally once daily, 4 weeks on treatment followed by 2 weeks off (42 day cycle). CGC-11047 will be administered on Days 1 and 8 of a 21 day cycle.<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | The MTD was defined as the dose below which one-third of at least 6 patients (2/6) experienced a dose limiting toxicity (DLT). DLTs had to occur during cycle 1 of treatment and had to be considered related to PG-11047: Any nonhematologic toxicity > Grade 3 lasting > 3 days Grade 4 thrombocytopenia Grade 4 Anemia on the next scheduled dosing day Grade 4 Neutropenia (lasting > than 5 days Any febrile neutropenia (Grade 3 or 4)) Inability to receive all scheduled doses of PG-11047 during the first dosing cycle due to drug related toxicity | End of Study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Safety |  | Ongoing | 
| Pharmacokinetics |  | End of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CGC-11047, cancer, advanced cancer, solid tumors, lymphoma