Metastatic Adenocarcinoma of Gastric Cardia, Metastatic Adenocarcinoma of the Esophagus, Unresectable Adenocarcinoma of Gastric Cardia, Unresectable Adenocarcinoma of the Esophagus
Conditions
Keywords
Unresectable, Metastatic, Esophagus, Gastric Cardia
Brief summary
In this study, Erlotinib and 5-Fluorouracil (5-FU), Leucovorin and Oxaliplatin (a regimen known also as FOLFOX-6) will be the chemotherapy study drugs. The main purpose of this study is to test the safety and effectiveness of this combination of chemotherapy drugs and to see how they affect your cancer. Another purpose of this study is to examine samples from your blood and tumor. This research will be done to better understand how subjects respond to treatment. Specifically, researchers will look at the way your genes and proteins respond to drugs like those used in this study.
Interventions
DRUGFOLFOX
Once every two weeks all patients will receive Oxaliplatin 85 mg/m2 IV, Leucovorin 400 mg/m2 IV and 5-FU 400 mg/m2 IV infusions
DRUG5-FU
5-FU 2400 mg/m2 IV will be given via pump for 46-48 hours at home.
DRUGErlotinib
All patients will also be given Erlotinib, 100 mg orally daily for the first 4 weeks. Those patients who have not experienced toxicities will increase the dose level to 150 mg daily. Patients who have toxicities will remain at the 100 mg dose level or lower if necessary.
Sponsors
University of California, Los Angeles
Sanofi
OSI Pharmaceuticals
Translational Oncology Research International
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Metastatic or unresectable adenocarcinoma of the upper gastrointestinal tract that can be measured in at least one dimension according to RECIST criteria by CT or MRI 2. Gastric adenocarcinomas may be included if the primary tumor arises within 5 cm of the anatomic gastro-esophageal junction (distal esophagus) or from the gastric cardia as indicated by either endoscope or imaging. 3. Previously untreated with chemotherapeutic agents for unresectable or metastatic disease. 4. Adjuvant chemotherapy and/or radiotherapy are allowed as long as no oxaliplatin was used in the past 12 months. 5. ECOG performance status 0 or 1 6. Age \> 18 years old. 7. Life expectancy greater than 6 months. 8. Peripheral neuropathy: must be \< grade 1 9. Absolute neutrophil count \> 1,500/mm3 10. Hemoglobin \> 9.0 g/dl 11. Platelet count \> 100,000/mm3 12. Hepatic Function: 1. Total Bilirubin \< or = to 1.5 x ULN 2. AST and ALT must be \< or = to 3.0 x ULN (\< or = to 5.0 x ULN if there is liver metastasis). 13. Creatinine clearance of \> 60 ml/min as calculated by the Cockcroft Gault formula. (Ccr = ((140-Age) X Wt (kg))/ (72 X SCr (mg/100ml) for males). (Ccr = ((140-Age) X Wt (kg))/ (72 X SCr (mg/100ml) x 0.85 for females) 14. Women of childbearing potential must have a negative pregnancy test by urine or serum testing. 15. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 4 months after the last treatment. 16. Patients must have signed IRB approved informed consent 17. Patients must have the ability to comply with study and follow-up procedures.
Exclusion criteria
1. Patients with known hypersensitivity to any components of oxaliplatin, leucovorin, 5-fluorouracil (or other fluoropyrimidines) or erlotinib. 2. Women who are breast-feeding or pregnant. 3. Presence of \> Grade 2 neuropathy 4. Patients with prior malignancy other than non-melanoma skin cancer or cervical carcinoma in situ within the past five years 5. Current or prior history of central nervous system or brain metastases 6. Any other medical conditions, which, in the opinion of the investigator, would preclude subjects to participate in the study. 7. Patients who have received chemotherapy, surgery or radiation therapy within 30 days prior to the first dose. 8. INR greater than 3.5 for patients on warfarin 9. Known HIV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate of Previously-untreated Patients With Unresectable or Metastatic Adenocarcinomas of the Upper Gastrointestinal Tract When Treated With the Combination of 5-fluorouracil, Leucovorin, Oxaliplatin, and Erlotinib. | 3.5 years | Per response evaluation criteria in solid tumors criteria (RECIST) for target lesions and assessed by computerized tomography (CT) scan. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | 3.5 years | Adverse event assessment by investigators and as reported by subjects from time of consent to 30 days after last dose. Up to 3.5 years. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FOLFOX Plus 5-FU and Erlotinib FOLFOX and Erlotinib: Once every two weeks all patients will receive Oxaliplatin 85 mg/m2 IV, Leucovorin 400 mg/m2 IV and 5-FU 400 mg/m2 IV infusions, after which 5-FU 2400 mg/m2 IV will be given via pump for 46-48 hours at home. All patients will also be given Erlotinib, 100 mg orally daily for the first 4 weeks. Those patients who have not experienced toxicities will increase the dose level to 150 mg daily. Patients who have toxicities will remain at the 100 mg dose level or lower if necessary. | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | FOLFOX Plus 5-FU and Erlotinib |
|---|---|
| Age, Continuous | 59 years |
| Eastern Cooperative Group performance status 0 | 23 participants |
| Eastern Cooperative Group performance status 1 | 15 participants |
| Neoadjuvant vs. Adjuvant Previous Radiation Therapy Adjuvant | 2 participants |
| Neoadjuvant vs. Adjuvant Previous Radiation Therapy Neoadjuvant | 4 participants |
| Neoadjuvant vs. Adjuvant Previous Radiation Therapy None | 32 participants |
| Oesophagus vs. gastro-oesophageal junction gastro-oesophageal junction (GEJ) | 26 participants |
| Oesophagus vs. gastro-oesophageal junction Oesophagus | 12 participants |
| Previous Chemotherapy Regimens Cisplatin/5-FU based (with neoadjuvant radiation) | 4 participants |
| Previous Chemotherapy Regimens Epirubicin/cisplatin/5-FU | 2 participants |
| Previous Chemotherapy Regimens Fluoropyrim/platinum (w/ adjuvant radiation) | 2 participants |
| Previous Chemotherapy Regimens None | 30 participants |
| Previous radiation therapy no | 32 participants |
| Previous radiation therapy yes | 6 participants |
| Previous Treatment Chemotherapy Adjuvant | 30 participants |
| Previous Treatment Chemotherapy Neoadjuvant | 8 participants |
| Previous Treatment: Surgery no | 33 participants |
| Previous Treatment: Surgery yes | 5 participants |
| Region of Enrollment United States | 38 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 38 |
| other Total, other adverse events | 38 / 38 |
| serious Total, serious adverse events | 7 / 38 |
Outcome results
Primary
Overall Response Rate of Previously-untreated Patients With Unresectable or Metastatic Adenocarcinomas of the Upper Gastrointestinal Tract When Treated With the Combination of 5-fluorouracil, Leucovorin, Oxaliplatin, and Erlotinib.
Per response evaluation criteria in solid tumors criteria (RECIST) for target lesions and assessed by computerized tomography (CT) scan. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time frame: 3.5 years
Population: 33 patients who were evaluable for response per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX Plus 5-FU and Erlotinib | Overall Response Rate of Previously-untreated Patients With Unresectable or Metastatic Adenocarcinomas of the Upper Gastrointestinal Tract When Treated With the Combination of 5-fluorouracil, Leucovorin, Oxaliplatin, and Erlotinib. | 51.5 percent of subjects that had response |
Secondary
Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib
Adverse event assessment by investigators and as reported by subjects from time of consent to 30 days after last dose. Up to 3.5 years.
Time frame: 3.5 years
Population: Number of subjects that experienced Grade 3 and 4 Adverse events associated with FOLFOX/5-FU/Erlotinib therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Diarrhea / dehydration | 9 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Anorexia | 5 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Nausea/Vomiting | 4 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Rash | 3 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Fatigue | 4 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Peripheral neuropathy | 3 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Neutropenia | 5 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Neutropenic Fever | 1 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | Hypokalemia | 2 participants |
| FOLFOX Plus 5-FU and Erlotinib | Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib | AST / ALT Elevation | 2 participants |