Radiation Therapy, Pemetrexed Disodium, and Carboplatin in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed By Surgery

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ClinicalTrials.gov Identifier: NCT00268437

Recruitment Status : Terminated (Trial closed early because, during an interim analysis, the primary endpoint fell short.)

First Posted : December 22, 2005

Results First Posted : March 27, 2015

Last Update Posted : July 6, 2016

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Alliance for Clinical Trials in Oncology

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Esophageal Cancer
Interventions	Drug: carboplatin Drug: Pemetrexed Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy
Enrollment	27

Participant Flow

Recruitment Details	This trial closed early because, during an interim analysis, the primary endpoint fell short. However, 26 eligible patients were accrued. Due to early closure not all the endpoints were analyzed.
Pre-assignment Details


Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description	Pemetrexed+Carboplatin+Radiation ca...
Arm/Group Description	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). Conventional surgery
Period Title: Overall Study
Started	27
Completed	26
Not Completed	1
Reason Not Completed
Ineligible	1

Baseline Characteristics

Arm/Group Title		Pemetrexed/Carboplatin
Arm/Group Description		Pemetrexed+Carboplatin+Radiation> ...
Arm/Group Description		Pemetrexed+Carboplatin+Radiation> > carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.> > Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.> > conventional surgery> > neoadjuvant therapy> > radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field).
Overall Number of Baseline Participants		27
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	27 participants
		66 (42 to 84)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	27 participants
	Female	7 25.9%
	Male	20 74.1%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	27 participants
United States		27

Outcome Measures

1.Primary Outcome


Title	Pathologic Complete Response Rate
Description	The proportion of pathologic complete responses will be estimated by t...
Description	The proportion of pathologic complete responses will be estimated by the number of pathologic complete responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true pathologic complete response rate will be calculated. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for Measurable disease is defined as at least one lesion whose longest diameter can be accurately measured as ≥2.0 cm with conventional techniques or as ≥1.0 cm with spiral CT. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung. However, CT is preferable.
Time Frame	Baseline to time of surgery (around 10 - 18 weeks post-baseline)

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description:	Pemetrexed+Carboplatin+Radiation ca...
Arm/Group Description:	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). conventional surgery
Overall Number of Participants Analyzed	26
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	23 (9 to 44)

2.Secondary Outcome


Title	Overall Survival
Description	Time from registration to death due to any cause.
Description	Time from registration to death due to any cause.
Time Frame	From baseline to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description:	Pemetrexed+Carboplatin+Radiation ca...
Arm/Group Description:	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). Conventional surgery
Overall Number of Participants Analyzed	26
Median (95% Confidence Interval) Unit of Measure: months
	17.8 (12.2 to 30.7)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Pemetrexed/Carboplatin
Arm/Group Description	Pemetrexed+Carboplatin+Radiation ca...
Arm/Group Description	Pemetrexed+Carboplatin+Radiation carboplatin: carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Pemetrexed: Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment. Radiation therapy: Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field). Conventional surgery
All-Cause Mortality
	Pemetrexed/Carboplatin
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events Serious Adverse Events
	Pemetrexed/Carboplatin
	Affected / at Risk (%)	# Events
Total	6/27 (22.22%)
Blood and lymphatic system disorders
Hemoglobin decreased ^† 1	1/27 (3.70%)	1
Cardiac disorders
Atrial fibrillation ^† 1	1/27 (3.70%)	1
Gastrointestinal disorders
Dysphagia ^† 1	1/27 (3.70%)	1
Esophageal fistula ^† 1	1/27 (3.70%)	1
Nausea ^† 1	1/27 (3.70%)	1
Small intestinal obstruction ^† 1	1/27 (3.70%)	1
Vomiting ^† 1	1/27 (3.70%)	1
Infections and infestations
Sepsis ^† 1	1/27 (3.70%)	1
Investigations
Leukocyte count decreased ^† 1	1/27 (3.70%)	1
Neutrophil count decreased ^† 1	1/27 (3.70%)	1
Platelet count decreased ^† 1	1/27 (3.70%)	1
Metabolism and nutrition disorders
Serum phosphate decreased ^† 1	1/27 (3.70%)	1
Serum potassium decreased ^† 1	1/27 (3.70%)	1
Renal and urinary disorders
Renal failure ^† 1	1/27 (3.70%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome ^† 1	1/27 (3.70%)	1
Dyspnea ^† 1	1/27 (3.70%)	1
Pneumonitis ^† 1	1/27 (3.70%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 6
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Pemetrexed/Carboplatin
	Affected / at Risk (%)	# Events
Total	27/27 (100.00%)
Blood and lymphatic system disorders
Hemoglobin decreased ^† 1	25/27 (92.59%)	59
Cardiac disorders
Atrial fibrillation ^† 1	2/27 (7.41%)	2
Myocardial ischemia ^† 1	1/27 (3.70%)	1
Pericardial effusion ^† 1	1/27 (3.70%)	1
Pericarditis ^† 1	1/27 (3.70%)	1
Gastrointestinal disorders
Constipation ^† 1	3/27 (11.11%)	4
Diarrhea ^† 1	11/27 (40.74%)	15
Dysphagia ^† 1	20/27 (74.07%)	48
Esophageal mucositis ^† 1	7/27 (25.93%)	10
Esophageal pain ^† 1	11/27 (40.74%)	21
Esophagitis ^† 1	16/27 (59.26%)	30
Nausea ^† 1	19/27 (70.37%)	36
Oesophagoscopy abnormal ^† 1	7/27 (25.93%)	9
Vomiting ^† 1	9/27 (33.33%)	12
General disorders
Death NOS ^† 1	1/27 (3.70%)	1
Edema limbs ^† 1	1/27 (3.70%)	1
Fatigue ^† 1	8/27 (29.63%)	12
Infections and infestations
Endocarditis infective ^† 1	1/27 (3.70%)	1
Pharyngitis ^† 1	1/27 (3.70%)	1
Pleural infection ^† 1	2/27 (7.41%)	2
Pneumonia ^† 1	2/27 (7.41%)	2
Small intestine infection ^† 1	1/27 (3.70%)	1
Soft tissue infection ^† 1	1/27 (3.70%)	1
Upper respiratory infection ^† 1	1/27 (3.70%)	1
Urinary tract infection ^† 1	1/27 (3.70%)	1
Wound infection ^† 1	1/27 (3.70%)	1
Injury, poisoning and procedural complications
Esophageal anastomotic leak ^† 1	1/27 (3.70%)	1
Vascular access complication ^† 1	1/27 (3.70%)	1
Investigations
Alkaline phosphatase increased ^† 1	1/27 (3.70%)	2
Aspartate aminotransferase increased ^† 1	8/27 (29.63%)	9
Blood bilirubin increased ^† 1	1/27 (3.70%)	1
Leukocyte count decreased ^† 1	24/27 (88.89%)	43
Lymphocyte count decreased ^† 1	1/27 (3.70%)	2
Neutrophil count decreased ^† 1	23/27 (85.19%)	37
Platelet count decreased ^† 1	23/27 (85.19%)	47
Weight loss ^† 1	2/27 (7.41%)	5
Metabolism and nutrition disorders
Anorexia ^† 1	4/27 (14.81%)	8
Blood glucose increased ^† 1	1/27 (3.70%)	1
Dehydration ^† 1	2/27 (7.41%)	3
Serum albumin decreased ^† 1	1/27 (3.70%)	1
Serum glucose decreased ^† 1	1/27 (3.70%)	1
Serum phosphate decreased ^† 1	1/27 (3.70%)	1
Serum potassium decreased ^† 1	1/27 (3.70%)	1
Musculoskeletal and connective tissue disorders
Chest wall pain ^† 1	1/27 (3.70%)	1
Muscle weakness ^† 1	1/27 (3.70%)	1
Neck pain ^† 1	1/27 (3.70%)	2
Nervous system disorders
Dysgeusia ^† 1	1/27 (3.70%)	1
Headache ^† 1	1/27 (3.70%)	1
Peripheral sensory neuropathy ^† 1	3/27 (11.11%)	8
Psychiatric disorders
Depression ^† 1	5/27 (18.52%)	5
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome ^† 1	2/27 (7.41%)	2
Aspiration ^† 1	1/27 (3.70%)	1
Atelectasis ^† 1	1/27 (3.70%)	1
Cough ^† 1	1/27 (3.70%)	1
Dyspnea ^† 1	8/27 (29.63%)	14
Hiccups ^† 1	1/27 (3.70%)	1
Hypoxia ^† 1	2/27 (7.41%)	3
Pleural effusion ^† 1	3/27 (11.11%)	3
Pneumonitis ^† 1	1/27 (3.70%)	1
Pneumothorax ^† 1	2/27 (7.41%)	2
Skin and subcutaneous tissue disorders
Decubitus ulcer ^† 1	1/27 (3.70%)	1
Erythema multiforme ^† 1	1/27 (3.70%)	1
Rash acneiform ^† 1	1/27 (3.70%)	1
Rash desquamating ^† 1	10/27 (37.04%)	12
Vascular disorders
Hypotension ^† 1	7/27 (25.93%)	10
Thrombosis ^† 1	2/27 (7.41%)	2
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 6

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Aminah Jatoi, M.D.
Organization:	Mayo Clinic
Phone:	507/284-4918
EMail:	jatoi.aminah@mayo.edu

Publications of Results:

Jatoi A, Soori G, Foster NR, Hiatt BK, Knost JA, Fitch TR, Callister MD, Nichols FC 3rd, Husted TM, Alberts SR. Phase II study of preoperative pemetrexed, carboplatin, and radiation followed by surgery for locally advanced esophageal cancer and gastroesophageal junction tumors. J Thorac Oncol. 2010 Dec;5(12):1994-8. doi: 10.1097/JTO.0b013e3181fb5c3e.

Katipamula R, Jatoi A, Foster NR, Nichols F, Rubin J, Callister M, Gunderson L, Alberts S. Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. Clin Med Oncol. 2008;2:223-5. Epub 2008 Apr 1.

Layout table for additonal information

Responsible Party:	Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:	NCT00268437
Other Study ID Numbers:	NCCTG-N044E NCI-2012-02678 ( Registry Identifier: CTRP (Clinical Trials Reporting System) ) CDR0000455635 ( Registry Identifier: PDQ (Physician Data Query) )
First Submitted:	December 20, 2005
First Posted:	December 22, 2005
Results First Submitted:	March 9, 2015
Results First Posted:	March 27, 2015
Last Update Posted:	July 6, 2016

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