A Study of Pemetrexed and Folic Acid Given Before Surgery (Neoadjuvant Treatment) to Patients With Rectal Cancer.

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00330915
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of this study is to help answer the following research questions:

If the study drug Pemetrexed can help patients with rectal cancer; If molecular biological parameters are correlated respectively changing due to cytotoxic treatment with Pemetrexed; To evaluate adverse events

Condition or Disease	Intervention/Treatment	Phase
Rectal Neoplasms	Drug: pemetrexed	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Feasibility Study of Pemetrexed Single Agent and Folic Acid Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: pemetrexed; 500 mg/m2, intravenous (IV), every 21 days x 3 cycles; Other Names: LY231514 Alimta

Outcome Measures

Primary Outcome Measures

1. Feasibility of Pemetrexed Prior to Surgery [3 cycles (21-day cycles)]

   Feasibility was defined as the ability to receive the total planned dose of Pemetrexed administered over a period of no more than 9 weeks permitting scheduling conflict. A ±5 percent variance in the calculated total dose was allowed.

Secondary Outcome Measures

1. Pathological Complete Response (pCR) [surgery following 3 cycles (21-day cycles) of chemotherapy]

   Pathological complete response was defined as the absence of any tumor cells.

2. Number of Participants With Complete Tumor Resection [surgery following 3 cycles (21-day cycles) of chemotherapy]

3. Number of Participants Receiving Sphincter Saving Surgery [surgery following 3 cycles (21-day cycles) of chemotherapy]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• no prior therapy for rectal cancer

• pathological/ cytological diagnosis of adenocarcinoma of the rectum. Patients must have operable rectal cancer that is amenable to surgery.

• adequate organ function

• Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1

• signed informed consent

• at least 18 years of age

• surgically sterile, postmenopausal (women) or compliant with a medically approved contraceptive regimen during and for 6 months after the treatment.

Exclusion Criteria:

• concurrent administration of any other anti-tumor therapy

• treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry

• serious concomitant systemic disorders

• previously completed or withdrawn from this study

• pregnant or breast-feeding

• second primary malignancy

• history of significant neurological or mental disorder, including seizures or dementia

• inability to interrupt aspirin or other nonsteroidal anto-inflammatory drugs (NSAIDs)

• presence of clinically relevant third space fluid collections that cannot be controlled by drainage or other procedure prior to the study entry

• inability or unwillingness to take folic acid, vitamin B12 or dexamethasone

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Göteborg		Sweden	41685

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5PM Eastern time (UTC/ GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00330915
• Other Study ID Numbers: 9732; H3E-MC-S077
• First Posted: May 29, 2006
• Last Update Posted: Jul 21, 2009
• Last Verified: Jun 1, 2009

• Additional relevant MeSH terms: Rectal Neoplasms; Pemetrexed

Study Results

Participant Flow

Arm/Group Title	Pemetrexed
Arm/Group Description	500 mg/m2, intravenous (IV), every 21 days x 3 cycles
Period Title: Overall Study
STARTED	37
COMPLETED	37
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pemetrexed
Arm/Group Description	500 mg/m2, intravenous (IV), every 21 days x 3 cycles
Overall Participants	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.3 (11.5)
Sex: Female, Male (Count of Participants)
Female	11 29.7%
Male	26 70.3%
Region of Enrollment (participants) [Number]
Sweden	37 100%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0 - Fully Active	37 100%
1 - Ambulatory, Restricted Strenuous Activity	0 0%
2 - Ambulatory, No Work Activities	0 0%
3 - Partially Confined to Bed, Limited Self Care	0 0%
4 - Completely Disabled	0 0%
Histopathological Diagnosis (participants) [Number]
G1 - Well-Differentiated	3 8.1%
G2 - Moderately Differentiated	25 67.6%
G3 - Poorly Differentiated	3 8.1%
Not Applicable	4 10.8%
Unspecified	2 5.4%
Race/Ethnicity (participants) [Number]
Caucasian	36 97.3%
East Asian	1 2.7%
Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Systolic Blood Pressure	136.5 (18.4)
Diastolic Blood Pressure	77.6 (9.1)
Body Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	173.4 (9.4)
Body Surface Area (meter squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meter squared]	2.0 (0.2)
Body Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	80.4 (15.2)
Heart Rate (beats per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats per minute]	80.4 (14.8)
Time Since Initial Pathological Diagnosis (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	3.2 (1.7)

Outcome Measures

1. Primary Outcome

Title	Feasibility of Pemetrexed Prior to Surgery
Description	Feasibility was defined as the ability to receive the total planned dose of Pemetrexed administered over a period of no more than 9 weeks permitting scheduling conflict. A ±5 percent variance in the calculated total dose was allowed.
Time Frame	3 cycles (21-day cycles)

Outcome Measure Data

Analysis Population Description

Number of participants enrolled.

Arm/Group Title	Pemetrexed
Arm/Group Description	500 mg/m2, intravenous (IV), every 21 days x 3 cycles
Measure Participants	37
Feasibility - Yes	33 89.2%
Feasibility - No	4 10.8%

2. Secondary Outcome

Title	Pathological Complete Response (pCR)
Description	Pathological complete response was defined as the absence of any tumor cells.
Time Frame	surgery following 3 cycles (21-day cycles) of chemotherapy

Outcome Measure Data

Analysis Population Description

Number of participants enrolled.

Arm/Group Title	Pemetrexed
Arm/Group Description	500 mg/m2, intravenous (IV), every 21 days x 3 cycles
Measure Participants	37
Complete Response - Yes	0 0%
Complete Response - No	1 2.7%
Complete Response - Not Determined	36 97.3%

3. Secondary Outcome

Title	Number of Participants With Complete Tumor Resection
Time Frame	surgery following 3 cycles (21-day cycles) of chemotherapy

Outcome Measure Data

Analysis Population Description

Number of participants enrolled.

Arm/Group Title	Pemetrexed
Arm/Group Description	500 mg/m2, intravenous (IV), every 21 days x 3 cycles
Measure Participants	37
Number [participants]	37 100%

4. Secondary Outcome

Title	Number of Participants Receiving Sphincter Saving Surgery
Time Frame	surgery following 3 cycles (21-day cycles) of chemotherapy

Outcome Measure Data

Analysis Population Description

Number of participants enrolled.

Arm/Group Title	Pemetrexed
Arm/Group Description	500 mg/m2, intravenous (IV), every 21 days x 3 cycles
Measure Participants	37
Surgery - Yes	25 67.6%
Surgery - No	12 32.4%

Adverse Events

Arm/Group Title	Pemetrexed
Arm/Group Description	500 mg/m2, intravenous (IV), every 21 days x 3 cycles
All Cause Mortality
	Pemetrexed
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pemetrexed
	Affected / at Risk (%)	# Events
Total	17/ (NaN)
Cardiac disorders
Atrial fibrillation	1/37 (2.7%)	1
Myocardial ischaemia	1/37 (2.7%)	1
Gastrointestinal disorders
Abdominal pain	1/37 (2.7%)	1
Diarrhoea	2/37 (5.4%)	2
Ileus	5/37 (13.5%)	5
Vomiting	1/37 (2.7%)	1
General disorders
Pyrexia	1/37 (2.7%)	1
Infections and infestations
Anorectal infection	1/37 (2.7%)	1
Infection	1/37 (2.7%)	1
Peritoneal abscess	1/37 (2.7%)	1
Pneumonia	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Gastrointestinal anastomotic leak	1/37 (2.7%)	1
Post procedural haemorrhage	1/37 (2.7%)	1
Procedural pain	1/37 (2.7%)	1
Wound complication	3/37 (8.1%)	3
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/37 (2.7%)	1
Vascular disorders
Haematoma	1/37 (2.7%)	1
Haemorrhage	1/37 (2.7%)	1
Other (Not Including Serious) Adverse Events
	Pemetrexed
	Affected / at Risk (%)	# Events
Total	37/ (NaN)
Blood and lymphatic system disorders
Neutropenia	2/37 (5.4%)	2
Eye disorders
Lacrimation increased	17/37 (45.9%)	18
Gastrointestinal disorders
Abdominal pain	2/37 (5.4%)	2
Constipation	2/37 (5.4%)	2
Diarrhoea	7/37 (18.9%)	7
Dry mouth	6/37 (16.2%)	6
Dyspepsia	3/37 (8.1%)	3
Frequent bowel movements	2/37 (5.4%)	2
Nausea	18/37 (48.6%)	23
General disorders
Fatigue	23/37 (62.2%)	33
Mucosal inflammation	4/37 (10.8%)	5
Pain	4/37 (10.8%)	5
Pyrexia	6/37 (16.2%)	7
Investigations
Alanine aminotransferase increased	4/37 (10.8%)	4
Haemoglobin decreased	2/37 (5.4%)	6
Neutrophil count decreased	3/37 (8.1%)	5
Weight decreased	2/37 (5.4%)	2
Metabolism and nutrition disorders
Anorexia	2/37 (5.4%)	2
Musculoskeletal and connective tissue disorders
Buttock pain	7/37 (18.9%)	7
Nervous system disorders
Dysgeusia	2/37 (5.4%)	2
Headache	7/37 (18.9%)	7
Renal and urinary disorders
Pollakiuria	2/37 (5.4%)	2
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	2/37 (5.4%)	2
Skin and subcutaneous tissue disorders
Hyperhidrosis	2/37 (5.4%)	3
Urticaria	9/37 (24.3%)	14
Vascular disorders
Haemorrhage	2/37 (5.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.