Cancer
Conditions
Keywords
cancer, advanced cancer, solid tumors, lymphoma, CGC-11047
Brief summary
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
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.
Interventions
DRUGCGC-11047 and gemcitabine
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).
DRUGCGC-11047 and docetaxel
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).
DRUGCGC-11047 and bevacizumab
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.
DRUGCGC-11047 and erlotinib
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.
DRUGCGC-11047 and cisplatin
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.
DRUGCGC-11047 and 5-flurouracil / leucovorin
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.
DRUGCGC-11047 and sunitinib
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.
Sponsors
Progen Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | End of Study | 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: 1. Any nonhematologic toxicity \> Grade 3 lasting \> 3 days 2. Grade 4 thrombocytopenia 3. Grade 4 Anemia on the next scheduled dosing day 4. Grade 4 Neutropenia (lasting \> than 5 days 5. Any febrile neutropenia (Grade 3 or 4)) 6. Inability to receive all scheduled doses of PG-11047 during the first dosing cycle due to drug related toxicity |
Secondary
| Measure | Time frame |
|---|---|
| Drug Safety | Ongoing |
| Pharmacokinetics | End of Study |
Countries
United States
Participant flow
Recruitment details
The recruitment period was June 2006 through March 2011, with last patient being treated May 2011. Patients were recruited through oncology clinics.
Pre-assignment details
There was no run-in phase. Patients were assigned to treatment arm based on their cancer type and which standard of care therapy was appropriate based on Investigators' discreation.
Participants by arm
| Arm | Count |
|---|---|
| PG11047/Gemcitabine PG-11047 (infusion on Days 1 and 15 of each cycle) in combination with Gemcitabine (1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle). | 12 |
| PG11047/Docetaxel PG-11047 (infusion on Day 1 of each 21 day cycle) in combination with Docetaxel (75 mg/m2 administered IV over 60 minutes every 21 days). | 9 |
| PG11047/Bevacizumab PG-11047 (infusion on Days 1, 8 and 15 of a 28 day cycle) in combination with Bevacizumab (5 mg/kg administered IV once every 14 days). | 34 |
| PG11047/Erlotinib PG-11047 (infusion on Days 1, 8 and 15 of a 28 day cycle) in combination with Erlotinib (150 mg taken orally every day of each 28-day cycle). | 34 |
| PG11047/Cisplatin Cisplatin: 80 mg/m2 administered IV over 1 hour once every 28 days. PG-11047 will be administered by infusion on Days 1, 8 and 15 of a 28 day cycle. | 48 |
| PG11047/5-Flurouracil PG-11047 (infusion on Days 1, 8 and 15 of a 28 day cycle) in combination with 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 weeks, repeated every 56 days). | 32 |
| PG11047/Sunitinib PG-11047 (infusion on Days 1 and 8 of a 21 day cycle) in combination with Sunitinib (50 mg orally once daily, 4 weeks on treatment followed by 2 weeks off (42 day cycle)). | 3 |
| Total | 172 |
Baseline characteristics
| Characteristic | PG11047/Docetaxel | PG11047/Bevacizumab | PG11047/Erlotinib | PG11047/Cisplatin | PG11047/Gemcitabine | PG11047/5-Flurouracil | PG11047/Sunitinib | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 8 Participants | 14 Participants | 17 Participants | 4 Participants | 12 Participants | 2 Participants | 62 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 26 Participants | 20 Participants | 31 Participants | 8 Participants | 20 Participants | 1 Participants | 110 Participants |
| Age, Continuous | 63.2 years STANDARD_DEVIATION 13.1 | 56.3 years STANDARD_DEVIATION 12.8 | 62.8 years STANDARD_DEVIATION 11 | 59.8 years STANDARD_DEVIATION 10.1 | 58.3 years STANDARD_DEVIATION 10.8 | 60.2 years STANDARD_DEVIATION 12.2 | 60.0 years STANDARD_DEVIATION 24.4 | 59.8 years STANDARD_DEVIATION 11.7 |
| Region of Enrollment United States | 9 participants | 34 participants | 34 participants | 48 participants | 12 participants | 32 participants | 3 participants | 172 participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 18 Participants | 19 Participants | 7 Participants | 14 Participants | 2 Participants | 80 Participants |
| Sex: Female, Male Male | 4 Participants | 19 Participants | 16 Participants | 29 Participants | 5 Participants | 18 Participants | 1 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 8 / 9 | 15 / 34 | 22 / 34 | 31 / 48 | 16 / 32 | 3 / 3 |
| serious Total, serious adverse events | 7 / 12 | 5 / 9 | 11 / 34 | 13 / 34 | 22 / 48 | 18 / 32 | 1 / 3 |
Outcome results
Primary
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: 1. Any nonhematologic toxicity \> Grade 3 lasting \> 3 days 2. Grade 4 thrombocytopenia 3. Grade 4 Anemia on the next scheduled dosing day 4. Grade 4 Neutropenia (lasting \> than 5 days 5. Any febrile neutropenia (Grade 3 or 4)) 6. Inability to receive all scheduled doses of PG-11047 during the first dosing cycle due to drug related toxicity
Time frame: End of Study
Population: Cohorts comprised 3 patients. When a patient experienced a treatment related toxicity qualifying as a DLT, up to 3 additional patients were to be enrolled at that dose. Patients who completed cycle 1 per protocol were evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG11047/Gemcitabine | Maximum Tolerated Dose (MTD) | NA mg |
| PG11047/Docetaxel | Maximum Tolerated Dose (MTD) | NA mg |
| PG11047/Bevacizumab | Maximum Tolerated Dose (MTD) | 590 mg |
| PG11047/Erlotinib | Maximum Tolerated Dose (MTD) | 590 mg |
| PG11047/Cisplatin | Maximum Tolerated Dose (MTD) | 590 mg |
| PG11047/5-Flurouracil | Maximum Tolerated Dose (MTD) | 590 mg |
| PG11047/Sunitinib | Maximum Tolerated Dose (MTD) | NA mg |
Secondary
Drug Safety
Time frame: Ongoing
Secondary
Pharmacokinetics
Time frame: End of Study