Pemetrexed Disodium/Observation in Treating Patients W/ Malignant Pleural Mesothelioma w/Out Progressive Disease After 1st Line Chemotherapy

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT01085630
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 72
• Locations: 145
• Arms: 2
• Actual Duration (Months): 132
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This randomized phase II trial is studying how well pemetrexed disodium or observation works in treating patients with malignant pleural mesothelioma without progressive disease after first-line chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Malignant Mesothelioma	Drug: pemetrexed disodium; Other: clinical observation	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine if maintenance therapy with pemetrexed disodium versus observation improves progression-free survival of patients with malignant pleural mesothelioma who have at least stable disease after completion of first-line therapy comprising pemetrexed disodium with cisplatin or carboplatin.

Secondary

• To determine the overall survival of patients treated with this regimen versus observation.

• To evaluate the frequency of responses in patients treated with this regimen.

• To assess the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to first-line chemotherapy regimen (cisplatin/pemetrexed disodium vs carboplatin/pemetrexed disodium), histologic subtype (epithelioid vs other) and number of courses received (< 6 vs 6).

• Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo observation until disease progression. After completion of study therapy, patients are followed up every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study of Maintenance Pemetrexed Versus Observation for Patients With Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy
• Actual Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Apr 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: pemetrexed disodium; Given IV; Other Names: 150399-23-8
Active Comparator: Arm II Patients undergo observation until disease progression.	Other: clinical observation

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Baseline up to 3 years]

   Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Secondary Outcome Measures

1. Overall Survival [Baseline up to 3 years]

   Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

2. Response Rate [Up to 3 years]

   The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. Response rates (including complete and partial response) will be tested using Fisher's exact test

3. Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) [Baseline up to 3 years]

   The number of patients reporting grade 3 or higher adverse events considered at least possibly related to study treatment as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed malignant pleural mesothelioma meeting 1 of the following cell types:

• Epithelial

• Sarcomatoid

• Mixed type

• Histologically documented malignant pleural mesothelioma, epithelial, sarcomatoid or mixed type, not amenable to surgical resection

• Prior treatment

• Currently receiving first-line treatment with pemetrexed + platinum; patients are to be registered to Cancer and Leukemia Group B (CALGB) 30901 no later than the last day of cycle 4 of first line therapy

• Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) are acceptable; prior intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy

• Prior surgical treatment is allowed

• Prior radiation therapy is allowed

• Non-pregnant and non-nursing; women of child bearing potential and men must agree to use an appropriate method of birth control throughout their participation in this study; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives (Norplant), or double barrier methods (diaphragm plus condom)

• RANDOMIZATION ELIGIBILITY CRITERIA

• Patients with complete response, partial response, or stable disease following 4, 5 or 6 cycles of first-line chemotherapy with pemetrexed AND either cisplatin or carboplatin; a maximum of 6 cycles of chemotherapy may have been given

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Granulocytes >= 1,500/ul

• Platelet count >= 100,000/ul

• Total bilirubin =< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2 x ULN

• Calculated creatinine clearance >= 45 ml/min

• Disease not amenable to surgery

• Must be enrolled on imaging protocol CALGB-580903

• Complete response, partial response, or stable disease after completion of 4 courses of first-line chemotherapy comprising pemetrexed disodium AND cisplatin or carboplatin

• Study therapy will begin within 9 weeks following day 1 of cycle 4 of first-line treatment

• No clinically significant pleural or peritoneal effusions that cannot be adequately managed by drainage before or during pemetrexed disodium

PATIENT CHARACTERISTICS:

• ECOG performance status of 0-1

• Life expectancy ≥ 12 weeks

• Granulocytes ≥ 1,500/μL

• Platelet count ≥ 100,000/μL

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST ≤ 2 times ULN

• Creatinine clearance ≥ 45 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No psychiatric illness that would prevent the patient from giving informed consent

• No second malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix unless curatively treated with no evidence of active disease for ≥ 5 years

• No medical conditions that, in the opinion of the treating physician, would make study treatment unreasonably hazardous for the patient including, but not limited to, the following:

• Ongoing or active infection such as HIV positivity

• Inability to take oral medications

• Psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) allowed

• Prior intrapleural cytotoxic chemotherapy not considered systemic chemotherapy

• Prior surgery allowed

• Prior radiotherapy allowed

• No concurrent palliative radiotherapy

• No concurrent hormones or other chemotherapeutic agents except for the following:

• Steroids for adrenal failure

• Hormones for nondisease-related conditions (e.g., insulin for diabetes)

• Intermittent use of dexamethasone as an antiemetic or premedication for pemetrexed disodium

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
3	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
4	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut	United States	06050
5	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
6	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
7	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
8	Illinois CancerCare - Bloomington	Bloomington	Illinois	United States	61701
9	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
10	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
11	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
12	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
13	Eureka Community Hospital	Eureka	Illinois	United States	61530
14	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
15	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
16	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
17	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
18	La Grange Memorial Hospital	La Grange	Illinois	United States	60525
19	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
20	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
21	OSF Holy Family Medical Center	Monmouth	Illinois	United States	61462
22	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
23	Community Cancer Center	Normal	Illinois	United States	61761
24	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
25	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
26	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
27	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
28	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
29	Proctor Hospital	Peoria	Illinois	United States	61614
30	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
31	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
32	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
33	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
34	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
35	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
36	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
37	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
38	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
39	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
40	Elkhart General Hospital	Elkhart	Indiana	United States	46515
41	Howard Community Hospital	Kokomo	Indiana	United States	46904
42	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
43	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
44	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
45	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
46	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
47	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
48	Michiana Hematology Oncology PC - La Porte	Westville	Indiana	United States	46391
49	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
50	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
51	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
52	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
53	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
54	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
55	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
56	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
57	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
58	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
59	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
60	Cancer Center of Kansas, PA - McPherson	McPherson	Kansas	United States	67460
61	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
62	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
63	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
64	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
65	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
66	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
67	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
68	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
69	CCOP - Wichita	Wichita	Kansas	United States	67214
70	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
71	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
72	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana	United States	70809
73	Ochsner Health Center - Covington	Covington	Louisiana	United States	70433
74	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana	United States	70115
75	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
76	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
77	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
78	Veterans Affairs Medical Center - Baltimore	Baltimore	Maryland	United States	21201
79	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
80	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
81	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
82	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
83	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
84	Hurley Medical Center	Flint	Michigan	United States	48503
85	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
86	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
87	Foote Memorial Hospital	Jackson	Michigan	United States	49201
88	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
89	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
90	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
91	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
92	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
93	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
94	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
95	St. John Macomb Hospital	Warren	Michigan	United States	48093
96	St. Joseph's Medical Center	Brainerd	Minnesota	United States	56401
97	Essentia Health - Duluth Clinic	Duluth	Minnesota	United States	55805-1983
98	CCOP - Duluth	Duluth	Minnesota	United States	55805
99	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
100	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota	United States	55455
101	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
102	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
103	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
104	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
105	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
106	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
107	Duke Cancer Institute	Durham	North Carolina	United States	27710
108	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
109	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
110	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
111	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
112	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
113	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
114	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
115	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
116	Cleveland Clinic Beachwood Family Health and Surgery Center	Beachwood	Ohio	United States	44122
117	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio	United States	44111
118	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
119	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
120	Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
121	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
122	Parma Community General Hospital	Parma	Ohio	United States	44129
123	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
124	Cleveland Clinic Foundation - Strongsville	Strongsville	Ohio	United States	44136
125	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
126	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
127	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
128	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
129	Willamette Falls Hospital	Oregon City	Oregon	United States	97045
130	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
131	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
132	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
133	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
134	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
135	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
136	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
137	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
138	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
139	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
140	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
141	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina	United States	29401
142	Danville Regional Medical Center	Danville	Virginia	United States	24541
143	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98664
144	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington	United States	98684
145	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Arkadiusz Dudek, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 3, 2018

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT01085630
• Other Study ID Numbers: CALGB-30901; CALGB-30901; U10CA180821; U10CA031946; CDR0000667496
• First Posted: Mar 12, 2010
• Last Update Posted: Aug 18, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Alliance for Clinical Trials in Oncology: epithelial mesothelioma; sarcomatous mesothelioma; stage II malignant mesothelioma; stage III malignant mesothelioma; stage IV malignant mesothelioma
• Additional relevant MeSH terms: Mesothelioma; Mesothelioma, Malignant; Pemetrexed

Study Results

Participant Flow

Pre-assignment Detail	19 enrolled patients were not randomized for the following reasons: progression during first-line therapy, patient refusal, new disease grade 4 brain tumor, patient expired prior to randomization, insufficient creatinine levels, > 1 week needed to randomize, prolonged adverse events, ineligible due to ECOG performance status being 2 or 3.

Arm/Group Title	Arm A (Observation)	Arm B (Pemetrexed)
Arm/Group Description	Patients undergo observation until disease progression.	Patients receive pemetrexed 500 mg/m2 IV over 10 minutes (or per institutional guidelines) every three weeks. Patients will continue treatment until disease progression or excess toxicity.
Period Title: Overall Study
STARTED	26	27
COMPLETED	22	27
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Arm A (Observation)	Arm B (Pemetrexed)	Total
Arm/Group Description	Patients undergo observation until disease progression.	Patients receive pemetrexed 500 mg/m2 IV over 10 minutes (or per institutional guidelines) every three weeks. Patients will continue treatment until disease progression or excess toxicity.	Total of all reporting groups
Overall Participants	22	27	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.1 (10.2)	71.0 (9.0)	69.7 (9.6)
Sex: Female, Male (Count of Participants)
Female	7 31.8%	6 22.2%	13 26.5%
Male	15 68.2%	21 77.8%	36 73.5%
Race/Ethnicity, Customized (Count of Participants)
Unknown	1 4.5%	3 11.1%	4 8.2%
White	21 95.5%	23 85.2%	44 89.8%
Black/African American	0 0%	1 3.7%	1 2%
Region of Enrollment (Count of Participants)
United States	22 100%	27 100%	49 100%
ECOG Performance Status (Count of Participants)
0	6 27.3%	9 33.3%	15 30.6%
1	16 72.7%	18 66.7%	34 69.4%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame	Baseline up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Observation)	Arm B (Pemetrexed)
Arm/Group Description	Patients undergo observation until disease progression.	Patients receive pemetrexed 500 mg/m2 IV over 10 minutes (or per institutional guidelines) every three weeks. Patients will continue treatment until disease progression or excess toxicity.
Measure Participants	22	27
Median (95% Confidence Interval) [months]	3.0	3.4

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame	Baseline up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Observation)	Arm B (Pemetrexed)
Arm/Group Description	Patients undergo observation until disease progression.	Patients receive pemetrexed 500 mg/m2 IV over 10 minutes (or per institutional guidelines) every three weeks. Patients will continue treatment until disease progression or excess toxicity.
Measure Participants	22	27
Median (95% Confidence Interval) [months]	11.8	16.3

3. Secondary Outcome

Title	Response Rate
Description	The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. Response rates (including complete and partial response) will be tested using Fisher's exact test
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

One patient on the observation arm did not submit any follow-up forms and withdrew consent to all follow-up and thus excluded in this analysis.

Arm/Group Title	Arm A (Observation)	Arm B (Pemetrexed)
Arm/Group Description	Patients undergo observation until disease progression.	Patients receive pemetrexed 500 mg/m2 IV over 10 minutes (or per institutional guidelines) every three weeks. Patients will continue treatment until disease progression or excess toxicity.
Measure Participants	21	27
Number (95% Confidence Interval) [percentage of participants]	0 0%	11.1 41.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Observation), Arm B (Pemetrexed)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2423
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
Description	The number of patients reporting grade 3 or higher adverse events considered at least possibly related to study treatment as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.
Time Frame	Baseline up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm B (Pemetrexed)
Arm/Group Description	Patients receive pemetrexed 500 mg/m2 IV over 10 minutes (or per institutional guidelines) every three weeks. Patients will continue treatment until disease progression or excess toxicity.
Measure Participants	27
Grade 3 Adverse Event	9 40.9%
Grade 4 Adverse Event	2 9.1%

Adverse Events

Time Frame	Adverse events were collected at the end of each cycle for patients randomized to the treatment arm; Up to 3 years.
Adverse Event Reporting Description	Each CTCAE term is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who received treatment (pemetrexed). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and appear in the SAE table.
Arm/Group Title	Arm B (Pemetrexed)
Arm/Group Description	Patients receive pemetrexed 500 mg/m2 IV over 10 minutes (or per institutional guidelines) every three weeks. Patients will continue treatment until disease progression or excess toxicity.
All Cause Mortality
	Arm B (Pemetrexed)
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Serious Adverse Events
	Arm B (Pemetrexed)
	Affected / at Risk (%)	# Events
Total	3/27 (11.1%)
Blood and lymphatic system disorders
Anemia	1/27 (3.7%)	1
Ear and labyrinth disorders
Hearing impaired	1/27 (3.7%)	2
Gastrointestinal disorders
Abdominal distension	1/27 (3.7%)	1
Abdominal pain	1/27 (3.7%)	1
Ascites	1/27 (3.7%)	1
Ileus	1/27 (3.7%)	1
Nausea	1/27 (3.7%)	1
General disorders
Fatigue	1/27 (3.7%)	2
Infections and infestations
Skin infection	1/27 (3.7%)	1
Urinary tract infection	1/27 (3.7%)	1
Investigations
Alanine aminotransferase increased	1/27 (3.7%)	1
Aspartate aminotransferase increased	1/27 (3.7%)	1
Creatinine increased	2/27 (7.4%)	2
INR increased	1/27 (3.7%)	1
Platelet count decreased	1/27 (3.7%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/27 (3.7%)	2
Hypoalbuminemia	2/27 (7.4%)	2
Hypocalcemia	1/27 (3.7%)	1
Hypokalemia	1/27 (3.7%)	1
Nervous system disorders
Peripheral sensory neuropathy	1/27 (3.7%)	2
Psychiatric disorders
Anxiety	1/27 (3.7%)	2
Renal and urinary disorders
Proteinuria	2/27 (7.4%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/27 (7.4%)	2
Pleural effusion	1/27 (3.7%)	1
Vascular disorders
Thromboembolic event	1/27 (3.7%)	2
Other (Not Including Serious) Adverse Events
	Arm B (Pemetrexed)
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Anemia	18/27 (66.7%)	101
Febrile neutropenia	1/27 (3.7%)	1
Cardiac disorders
Atrial fibrillation	1/27 (3.7%)	1
Palpitations	1/27 (3.7%)	1
Sinus tachycardia	1/27 (3.7%)	1
Ear and labyrinth disorders
Hearing impaired	1/27 (3.7%)	3
Vertigo	1/27 (3.7%)	1
Eye disorders
Dry eye	1/27 (3.7%)	1
Eyelid function disorder	1/27 (3.7%)	2
Watering eyes	2/27 (7.4%)	2
Gastrointestinal disorders
Abdominal distension	1/27 (3.7%)	1
Abdominal pain	4/27 (14.8%)	10
Bloating	1/27 (3.7%)	16
Constipation	7/27 (25.9%)	56
Diarrhea	4/27 (14.8%)	14
Dry mouth	1/27 (3.7%)	14
Dyspepsia	1/27 (3.7%)	1
Dysphagia	1/27 (3.7%)	4
Hemorrhoids	1/27 (3.7%)	2
Mucositis oral	3/27 (11.1%)	13
Nausea	13/27 (48.1%)	88
Upper gastrointestinal hemorrhage	1/27 (3.7%)	1
Vomiting	5/27 (18.5%)	9
General disorders
Chills	1/27 (3.7%)	3
Edema limbs	4/27 (14.8%)	13
Fatigue	22/27 (81.5%)	170
Fever	2/27 (7.4%)	3
Infusion site extravasation	2/27 (7.4%)	2
Localized edema	2/27 (7.4%)	10
Non-cardiac chest pain	4/27 (14.8%)	23
Pain	6/27 (22.2%)	10
Infections and infestations
Anorectal infection	1/27 (3.7%)	6
Bronchial infection	1/27 (3.7%)	1
Eye infection	1/27 (3.7%)	2
Lung infection	1/27 (3.7%)	2
Prostate infection	1/27 (3.7%)	1
Skin infection	2/27 (7.4%)	14
Tooth infection	2/27 (7.4%)	3
Injury, poisoning and procedural complications
Fall	1/27 (3.7%)	3
Investigations
Alanine aminotransferase increased	5/27 (18.5%)	14
Alkaline phosphatase increased	3/27 (11.1%)	10
Aspartate aminotransferase increased	3/27 (11.1%)	5
CD4 lymphocytes decreased	1/27 (3.7%)	1
Creatinine increased	5/27 (18.5%)	11
GGT increased	1/27 (3.7%)	1
Lymphocyte count decreased	8/27 (29.6%)	68
Lymphocyte count increased	1/27 (3.7%)	3
Neutrophil count decreased	1/27 (3.7%)	1
Platelet count decreased	3/27 (11.1%)	6
Weight gain	1/27 (3.7%)	1
White blood cell decreased	2/27 (7.4%)	18
Metabolism and nutrition disorders
Acidosis	1/27 (3.7%)	1
Anorexia	5/27 (18.5%)	8
Dehydration	1/27 (3.7%)	1
Hyperglycemia	8/27 (29.6%)	72
Hyperkalemia	2/27 (7.4%)	9
Hypernatremia	1/27 (3.7%)	3
Hypoalbuminemia	4/27 (14.8%)	37
Hypocalcemia	1/27 (3.7%)	1
Hypomagnesemia	2/27 (7.4%)	7
Hyponatremia	4/27 (14.8%)	26
Musculoskeletal and connective tissue disorders
Arthralgia	2/27 (7.4%)	6
Arthritis	1/27 (3.7%)	4
Back pain	4/27 (14.8%)	8
Chest wall pain	2/27 (7.4%)	2
Flank pain	1/27 (3.7%)	14
Myalgia	1/27 (3.7%)	1
Pain in extremity	1/27 (3.7%)	4
Nervous system disorders
Dizziness	4/27 (14.8%)	15
Peripheral motor neuropathy	1/27 (3.7%)	4
Peripheral sensory neuropathy	5/27 (18.5%)	31
Psychiatric disorders
Anxiety	2/27 (7.4%)	27
Insomnia	1/27 (3.7%)	13
Renal and urinary disorders
Chronic kidney disease	1/27 (3.7%)	5
Proteinuria	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/27 (11.1%)	5
Dyspnea	6/27 (22.2%)	46
Nasal congestion	1/27 (3.7%)	8
Pleural effusion	1/27 (3.7%)	2
Pleuritic pain	1/27 (3.7%)	1
Productive cough	1/27 (3.7%)	1
Respiratory failure	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders - Other, specify	1/27 (3.7%)	1
Wheezing	1/27 (3.7%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/27 (3.7%)	14
Hyperhidrosis	1/27 (3.7%)	19
Purpura	1/27 (3.7%)	1
Rash maculo-papular	2/27 (7.4%)	5
Skin and subcutaneous tissue disorders - Other, specify	1/27 (3.7%)	5
Urticaria	1/27 (3.7%)	1
Vascular disorders
Flushing	1/27 (3.7%)	3
Hot flashes	1/27 (3.7%)	21
Hypertension	2/27 (7.4%)	25
Hypotension	1/27 (3.7%)	2
Thromboembolic event	2/27 (7.4%)	5
Vascular disorders - Other, specify	1/27 (3.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.