Study of Erlotinib and Chemotherapy for Unresectable or Metastatic Cancer of the Esophagus and Gastric Cardia

• Sponsor: Translational Oncology Research International (Other)
• Overall Status: Completed
• CT.gov ID: NCT00591123
• Collaborator: University of California, Los Angeles (Other), Sanofi (Industry), OSI Pharmaceuticals (Industry)
• Enrollment: 38
• Locations: 2
• Arm: 1
• Duration (Months): 93
• Patients Per Site: 19
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Unresectable Adenocarcinoma of the Esophagus; Metastatic Adenocarcinoma of the Esophagus; Unresectable Adenocarcinoma of Gastric Cardia; Metastatic Adenocarcinoma of Gastric Cardia	Drug: FOLFOX; Drug: 5-FU; Drug: Erlotinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Erlotinib and Modified FOLFOX-6 (5-Fluorouracil, Leucovorin and Oxaliplatin) in Previously Untreated Patients With Unresectable or Metastatic Adenocarcinoma of the Esophagus and Gastric Cardia
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: FOLFOX, plus 5-FU and Erlotinib single arm

Drug: FOLFOX; 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; Other Names: Leucovorin Calcium 5-FU Oxaliplatin ; Drug: 5-FU; 5-FU 2400 mg/m2 IV will be given via pump for 46-48 hours at home.; Other Names: Fluorouracil ; Drug: Erlotinib; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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:

13. Total Bilirubin < or = to 1.5 x ULN

14. AST and ALT must be < or = to 3.0 x ULN (< or = to 5.0 x ULN if there is liver metastasis).

15. 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)

1. Women of childbearing potential must have a negative pregnancy test by urine or serum testing.

2. 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.

3. Patients must have signed IRB approved informed consent

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Translational Oncology Research International (TORI) Network	Los Angeles	California	United States	90095
2	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Translational Oncology Research International
• University of California, Los Angeles
• Sanofi
• OSI Pharmaceuticals

Investigators

• Principal Investigator: Zev Wainberg, MD, University of California, Los Angeles
• Study Director: Fairooz Kabbinavar, MD, UCLA - TORI
• Study Chair: J Randolph Hecht, MD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Translational Oncology Research International
• ClinicalTrials.gov Identifier: NCT00591123
• Other Study ID Numbers: TORI GI-05; BB-IND 77,805
• First Posted: Jan 11, 2008
• Last Update Posted: Oct 1, 2021
• Last Verified: Feb 1, 2016

• Keywords provided by Translational Oncology Research International: Unresectable; Metastatic; Esophagus; Gastric Cardia
• Additional relevant MeSH terms: Adenocarcinoma; Esophageal Neoplasms; Leucovorin; Fluorouracil; Oxaliplatin; Erlotinib Hydrochloride; Levoleucovorin

Study Results

Participant Flow

Arm/Group Title	FOLFOX Plus 5-FU and Erlotinib
Arm/Group Description	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.
Period Title: Overall Study
STARTED	38
COMPLETED	38
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	FOLFOX Plus 5-FU and Erlotinib
Arm/Group Description	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.
Overall Participants	38
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	5 13.2%
Male	33 86.8%
Region of Enrollment (participants) [Number]
United States	38 100%
Eastern Cooperative Group performance status (participants) [Number]
0	23 60.5%
1	15 39.5%
Previous Treatment: Surgery (participants) [Number]
yes	5 13.2%
no	33 86.8%
Previous Treatment Chemotherapy (participants) [Number]
Neoadjuvant	8 21.1%
Adjuvant	30 78.9%
Previous Chemotherapy Regimens (participants) [Number]
Fluoropyrim/platinum (w/ adjuvant radiation)	2 5.3%
Cisplatin/5-FU based (with neoadjuvant radiation)	4 10.5%
Epirubicin/cisplatin/5-FU	2 5.3%
None	30 78.9%
Previous radiation therapy (participants) [Number]
yes	6 15.8%
no	32 84.2%
Neoadjuvant vs. Adjuvant Previous Radiation Therapy (participants) [Number]
Neoadjuvant	4 10.5%
Adjuvant	2 5.3%
None	32 84.2%
Oesophagus vs. gastro-oesophageal junction (participants) [Number]
Oesophagus	12 31.6%
gastro-oesophageal junction (GEJ)	26 68.4%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

33 patients who were evaluable for response per protocol

Arm/Group Title	FOLFOX Plus 5-FU and Erlotinib
Arm/Group Description	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.
Measure Participants	33
Number [percent of subjects that had response]	51.5

2. Secondary Outcome

Title	Toxicity of the Combination of FOLFOX, 5-FU, and Erlotinib
Description	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

Outcome Measure Data

Analysis Population Description

Number of subjects that experienced Grade 3 and 4 Adverse events associated with FOLFOX/5-FU/Erlotinib therapy

Arm/Group Title	FOLFOX Plus 5-FU and Erlotinib
Arm/Group Description	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.
Measure Participants	38
Diarrhea / dehydration	9 23.7%
Anorexia	5 13.2%
Nausea/Vomiting	4 10.5%
Rash	3 7.9%
Fatigue	4 10.5%
Peripheral neuropathy	3 7.9%
Neutropenia	5 13.2%
Neutropenic Fever	1 2.6%
Hypokalemia	2 5.3%
AST / ALT Elevation	2 5.3%

Adverse Events

Time Frame	consent until 30 days post treatment
Adverse Event Reporting Description	Systemic adverse event assessment occurred every 14 days through investigator assessment during Treatment Period.
Arm/Group Title	Single Arm
Arm/Group Description	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.
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	7/38 (18.4%)
Blood and lymphatic system disorders
Elevated International Normalized Ratio (INR)	1/38 (2.6%)	1
Gastrointestinal disorders
Vomiting	1/38 (2.6%)	1
Diarrhea	3/38 (7.9%)	3
General disorders
Malnutrition	2/38 (5.3%)	2
Nausea	1/38 (2.6%)	1
Abdominal Pain	1/38 (2.6%)	2
Infections and infestations
Neutropenic Fever	1/38 (2.6%)	1
Septic Shock	1/38 (2.6%)	1
Finger Infection	1/38 (2.6%)	1
Injury, poisoning and procedural complications
Sacral Fracture	1/38 (2.6%)	1
Cranial Hematoma	1/38 (2.6%)	1
Metabolism and nutrition disorders
Anorexia	1/38 (2.6%)	1
Musculoskeletal and connective tissue disorders
Intractable Back Pain	1/38 (2.6%)	1
Nervous system disorders
Altered Mental State	1/38 (2.6%)	1
Renal and urinary disorders
Renal Failure	1/38 (2.6%)	1
Inability to Urinate	1/38 (2.6%)	1
Hematuria	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	1/38 (2.6%)	1
Surgical and medical procedures
diskectomy	1/38 (2.6%)	1
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	38/38 (100%)
Blood and lymphatic system disorders
Alkaline Phosphatase - elevated	11/38 (28.9%)	13
Alanine Aminotransferase - elevated	6/38 (15.8%)	7
Anemia	16/38 (42.1%)	19
Aspartate Aminotransferase - elevated	9/38 (23.7%)	12
Creatinine - elevated	2/38 (5.3%)	2
Diabetes mellitus	1/38 (2.6%)	2
Hyperalbuminemia	1/38 (2.6%)	1
Hypercholesterolemia	1/38 (2.6%)	1
Hyperglycemia	9/38 (23.7%)	11
Hyperkalemia	1/38 (2.6%)	1
Hypertension	1/38 (2.6%)	1
Hypoalbuminemia	7/38 (18.4%)	8
Hypocalcemia	7/38 (18.4%)	8
Hypokalemia	17/38 (44.7%)	24
Hypomagnesia	2/38 (5.3%)	2
Hyponatremia	5/38 (13.2%)	6
Hypotension	4/38 (10.5%)	5
Hypoxia	1/38 (2.6%)	1
International Normalized Ratio (INR) - elevated	2/38 (5.3%)	2
Leukopenia	15/38 (39.5%)	24
Lymphopenia	6/38 (15.8%)	11
Neutropenia	14/38 (36.8%)	32
Sepsis	1/38 (2.6%)	1
Serum Chloride - Decrease	2/38 (5.3%)	2
Serum Protein - Decreased	1/38 (2.6%)	1
Thrombocytopenia	1/38 (2.6%)	1
Cardiac disorders
Cardiac infarction	1/38 (2.6%)	1
Palpitation	1/38 (2.6%)	1
Tachycardia	5/38 (13.2%)	6
Ear and labyrinth disorders
Odynophagia	2/38 (5.3%)	2
Rhinitis	2/38 (5.3%)	2
Sinusitis	1/38 (2.6%)	1
Eye disorders
Blepharitis	1/38 (2.6%)	1
Blurred vision	2/38 (5.3%)	2
Ocular - drainage	1/38 (2.6%)	1
Ocular - ruptured vessel	1/38 (2.6%)	1
Gastrointestinal disorders
Abdominal distention	1/38 (2.6%)	1
Blood in stool	2/38 (5.3%)	2
Diarrhea	28/38 (73.7%)	53
Flatulence	3/38 (7.9%)	4
GERD	1/38 (2.6%)	1
Heart burn	1/38 (2.6%)	1
Hematemesis	2/38 (5.3%)	2
Hemorrhoid	1/38 (2.6%)	1
Obstruction - GI small bowel NOS	1/38 (2.6%)	1
Perforation gastrointestinal tract	1/38 (2.6%)	1
General disorders
Alopecia	6/38 (15.8%)	7
Bloating	5/38 (13.2%)	6
Cachexia	1/38 (2.6%)	1
Chills	1/38 (2.6%)	1
Cold sensitivity	5/38 (13.2%)	5
Cold-like symptoms	3/38 (7.9%)	5
Constipation	14/38 (36.8%)	14
Cramps - limbs	3/38 (7.9%)	3
Dehydration	14/38 (36.8%)	15
Diaphoresis	1/38 (2.6%)	1
Dizziness	4/38 (10.5%)	5
Dry eye	2/38 (5.3%)	2
Dry heaves	1/38 (2.6%)	1
Dry mouth	4/38 (10.5%)	4
Dry Nose	1/38 (2.6%)	1
Dry skin	9/38 (23.7%)	10
Dyspepsia	3/38 (7.9%)	5
Dysphagia	5/38 (13.2%)	6
Edema	7/38 (18.4%)	12
Esophagitis	1/38 (2.6%)	1
Facial flushing	1/38 (2.6%)	1
Fatigue	24/38 (63.2%)	37
Fever	2/38 (5.3%)	2
Flu-like syndrome	1/38 (2.6%)	1
Folliculitis	1/38 (2.6%)	1
Gait-Walking	1/38 (2.6%)	1
Glossitis	1/38 (2.6%)	1
Hand and Foot Syndrome	3/38 (7.9%)	4
Hemorrhage (GI, gums, nose, upper GI)	5/38 (13.2%)	5
Hemorrhage (nose, oral cavity)	2/38 (5.3%)	4
Hiccups	2/38 (5.3%)	2
Hypothermia	2/38 (5.3%)	2
Lactose intolerance	1/38 (2.6%)	1
Mental status	1/38 (2.6%)	1
Mood alteration - anxiety	7/38 (18.4%)	7
Mood alteration - depression	6/38 (15.8%)	9
Mucositis - oral cavity	15/38 (39.5%)	17
Nail Changes	1/38 (2.6%)	1
Nausea	21/38 (55.3%)	31
Neutropenic fever	1/38 (2.6%)	1
Night sweats	1/38 (2.6%)	1
Pain	29/38 (76.3%)	48
Performance Status Decrease	3/38 (7.9%)	4
Rigors-Chills	3/38 (7.9%)	3
Somnolence	1/38 (2.6%)	1
Stomatitis	1/38 (2.6%)	1
Sweating	2/38 (5.3%)	2
Syncope	2/38 (5.3%)	2
Taste alteration	5/38 (13.2%)	7
Urinary retention	1/38 (2.6%)	1
Voice changes	1/38 (2.6%)	1
Vomiting	16/38 (42.1%)	22
Weakness	10/38 (26.3%)	15
Weight loss	17/38 (44.7%)	22
Hepatobiliary disorders
Hyperbilirubinemia	4/38 (10.5%)	7
Jaundice	1/38 (2.6%)	1
Infections and infestations
Infection	10/38 (26.3%)	15
Infection (skin, upper airway, pneumonia)	4/38 (10.5%)	4
Thrush	1/38 (2.6%)	1
Metabolism and nutrition disorders
Anorexia	21/38 (55.3%)	24
Hot flashes	1/38 (2.6%)	1
Metabolic acidosis	1/38 (2.6%)	1
Musculoskeletal and connective tissue disorders
Fracture	1/38 (2.6%)	1
Joint effusion - Elbow	1/38 (2.6%)	1
Myotonia	1/38 (2.6%)	1
Nervous system disorders
Neuropathy	2/38 (5.3%)	3
Neuropathy - motor	1/38 (2.6%)	2
Neuropathy - sensory	22/38 (57.9%)	38
Renal and urinary disorders
Hematuria	2/38 (5.3%)	2
Renal failure	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Bronchitis	1/38 (2.6%)	1
Cough	6/38 (15.8%)	6
Dyspnea	10/38 (26.3%)	10
Wheezing	1/38 (2.6%)	1
Skin and subcutaneous tissue disorders
Erythema	1/38 (2.6%)	1
Pallor	1/38 (2.6%)	1
Pruritis	3/38 (7.9%)	3
Rash	30/38 (78.9%)	55
Hyperpigmentation - portacath site	1/38 (2.6%)	1
Skin Irritation	1/38 (2.6%)	1
Papule lower extremities	1/38 (2.6%)	1
Papule upper chest	1/38 (2.6%)	1
Skin abrasion	1/38 (2.6%)	1
Urticaria	2/38 (5.3%)	3
Vitiligo	1/38 (2.6%)	1
Vascular disorders
Cerebrovascular accident (CVA)	1/38 (2.6%)	1
Hematoma	1/38 (2.6%)	1
Thrombosis-Embolism	3/38 (7.9%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.