CompletedNCT00216203Updated Sep 29, 2016Results posted

Pemetrexed Plus Cetuximab in Patients With Recurrent Non Small Cell Lung Cancer

A Phase 1/2 interventional study of Pemetrexed and Cetuximab in Non-Small Cell Lung Cancer, sponsored by Nasser Hanna, M.D.. Completed at 11 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-09-29.

Sponsored by Nasser Hanna, M.D. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 36
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

Both pemetrexed and cetuximab have single agent activity in NSCLC and non-overlapping toxicity profiles. While 2-drug combination therapy has proven superior to single agent therapy in the first-line setting of NSCLC, no such phase III trials have been reported in the second-line setting. Therefore, the purpose of this study is to determine the feasibility of combining these drugs, assessing the toxicity profile, determining the MTD and evaluating the activity of the combination in an expanded phase II setting. If the combination appears to have promising activity, further evaluation of this regimen may be warranted comparing it to single agent pemetrexed or cetuximab alone.

Read the detailed description

OUTLINE: This is a multi-center study.

Week 1 (day 1):

Cetuximab 400mg/m2

Week 2 (Cycle 1, Day 1):

Cetuximab 250mg/m2 plus premetrexed at the assigned dose level.

Patients will be treated with cetuximab on day 1, 8, 15 of each 21 day cycle.

Patients will be treated with pemetrexed on day 1 of each 21 day cycle for a maximum of 6 cycles.

Acceptable toxicity and SD, PR or CR: treat up to 6 cycles then continue cetuximab weekly until PD or excess toxicity

Performance status: ECOG 0-2

Life expectancy: At least 12 weeks

Hematopoietic:

ANC > 1,500/mm3
Platelets > 100,000/mm3

Hepatic:

Bilirubin less than or equal to the upper limit of normal (ULN)
Aspartate aminotransferase (AST) \< 1.5 X ULN. AST may be \< 5 X ULN for patients with liver metastases
Alkaline phosphatase \< 5 X ULN

Renal:

Calculated creatinine clearance > 45 mL/min (by Cockcroft-Gault)

Cardiovascular:

No significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, and congestive heart failure)

Pulmonary:

Not specified

Conditions studied

Non-Small Cell Lung Cancer

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Keywords

Non-Small Cell Lung Cancer

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 36 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

Nasser Hanna, M.D. is the lead sponsor of 8 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Histologic or cytologic diagnosis of NSCLC
Recurrent or metastatic disease that is not amenable to curative therapyMeasurable disease according to RECIST
At least one prior platinum containing regimen for either locally advanced or metastatic disease
Prior chemotherapy must be completed at least 21 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxicity effects of the regimen
Ability and willingness to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period
Prior radiation therapy allowed to \< 25% of the bone marrow
Negative pregnancy test

Exclusion criteria

Exclusion Criteria:

No active infection that in the opinion of the investigator would compromise the subject's ability to tolerate therapy.
No serious concomitant systemic disorders that would compromise the safety of the subject or compromise the subject's ability to complete the study, at the discretion of the investigator.
No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for at least 2 years.
No major thoracic or abdominal surgery within 30 days prior to being registered for protocol therapy.
No current breastfeeding

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 36 participants (actual)

Study arms

Experimental
Investigational Treatment
Pemetrexed + cetuximab for patients with recurrent non-small cell lung cancer.
Drug: Pemetrexed · Drug: Cetuximab

Interventions

DrugPemetrexed
Pemetrexed at the assigned dose, day 1 of each 21 day cycle for a maximum of 6 cycles
DrugCetuximab
Cetuximab 400 mg/m2, week 1, day 1 Cetuximab 250 mg/m2, day 1, 8, 15 of each 21 day cycle

What researchers measure

Primary outcomes

Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cetuximab
The primary objective of the phase I portion of this study is to define the maximum tolerated dose (MTD) of the combination of pemetrexed and cetuximab
Time frame: 12 months
Time To Progression (TTP)
The primary objective of the phase II portion is to estimate the time to progression of this combination, evaluated per RECIST criteria where 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: 24 Months

Secondary outcomes

Median Survival Time
Time frame: 24 Months
Toxicity and Safety Profile
Time frame: 12 months
Clinical Benefit Rate
Clinical Benefit Rate (CR + PR + SD lasting more than 90 days)
Time frame: 12 months

Results

Posted Jun 2, 2016

Participant flow

Participant flow — Overall Study
Milestone	Pemetrexed + Cetuximab
Started	36
Completed	34
Not completed	2
Withdrew: Withdrawal by subject	2

Outcome measures

PrimaryMaximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cetuximab

The primary objective of the phase I portion of this study is to define the maximum tolerated dose (MTD) of the combination of pemetrexed and cetuximab

Time frame:: 12 months
Reported as:: Number · mg/m^2 every 21 days

Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cetuximab
mg/m^2 every 21 days	Investigational Treatment
Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cetuximab	750

PrimaryTime To Progression (TTP)

The primary objective of the phase II portion is to estimate the time to progression of this combination, evaluated per RECIST criteria where 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:: 24 Months
Reported as:: Median · Weeks

Time To Progression (TTP)
Weeks	Pemetrexed + Cetuximab
Time To Progression (TTP)	14.6 (6.0 to 78.7)

SecondaryMedian Survival Time

Time frame:: 24 Months
Reported as:: Median · weeks

Median Survival Time
weeks	Pemetrexed + Cetuximab
Median Survival Time	42.0 (8.6 to 103.9)

SecondaryToxicity and Safety Profile

Time frame:: 12 months
Reported as:: Number · percentage of particpants

Toxicity and Safety Profile
percentage of particpants	Pemetrexed + Cetuximab
Acne-like rash: Phase I - Any Grade	58.3
Acne-like rash: Phase I - Grade 3/4	16.7
Acne-like rash: Phase II - Any Grade	57
Acne-like rash: Phase II - Grade 3/4	23.8
ALT elevation: Phase I - Any Grade	33.3
ALT elevation: Phase I - Grade 3/4	16.7
ALT elevation: Phase II - Any Grade	0
ALT elevation: Phase II - Grade 3/4	0
Anemia: Phase I - Any Grade	0
Anemia: Phase I - Grade 3/4	0
Anemia: Phase II - Any Grade	14.3
Anemia: Phase II - Grade 3/4	0
Thrombocytopenia: Phase I - Any Grade	8.3
Thrombocytopenia: Phase I - Grade 3/4	0
Thrombocytopenia: Phase II - Any Grade	14.3
Thrombocytopenia: Phase II - Grade 3/4	0
Neutropenia: Phase I - Any Grade	8.3
Neutropenia: Phase I - Grade 3/4	0
Neutropenia: Phase II - Any Grade	4.8
Neutropenia: Phase II - Grade 3/4	4.8
Febrile Neutropenia: Phase I - Any Grade	8.3
Febrile Neutropenia: Phase I - Grade 3/4	8.3
Febrile Neutropenia: Phase II - Any Grade	0
Febrile Neutropenia: Phase II - Grade 3/4	0
Dizziness: Phase I - Any Grade	8.3
Dizziness: Phase I - Grade 3/4	8.3
Dizziness: Phase II - Any Grade	19
Dizziness: Phase II - Grade 3/4	4.8
Dyspnea: Phase I - Any Grade	25
Dyspnea: Phase I - Grade 3/4	8.3
Dyspnea: Phase II - Any Grade	33.3
Dyspnea: Phase II - Grade 3/4	0
Cough: Phase I - Any Grade	25
Cough: Phase I - Grade 3/4	0
Cough: Phase II - Any Grade	28.6
Cough: Phase II - Grade 3/4	0
Fatigue: Phase I - Any Grade	33.3
Fatigue: Phase I - Grade 3/4	0
Fatigue: Phase II - Any Grade	76
Fatigue: Phase II - Grade 3/4	4.8
Anorexia: Phase I - Any Grade	33.3
Anorexia: Phase I - Grade 3/4	0
Anorexia: Phase II - Any Grade	19
Anorexia: Phase II - Grade 3/4	4.8
Mucositis: Phase I - Any Grade	41.7
Mucositis: Phase I - Grade 3/4	0
Mucositis: Phase II - Any Grade	38
Mucositis: Phase II - Grade 3/4	4.8
Nausea: Phase I - Any Grade	33.3
Nausea: Phase I - Grade 3/4	0
Nausea: Phase II - Any Grade	28.6
Nausea: Phase II - Grade 3/4	0
Diarrhea: Phase I - Any Grade	33.3
Diarrhea: Phase I - Grade 3/4	0
Diarrhea: Phase II - Any Grade	33.3
Diarrhea: Phase II - Grade 3/4	9.5
Constipation: Phase I - Any Grade	16.7
Constipation: Phase I - Grade 3/4	0
Constipation: Phase II - Any Grade	23.8
Constipation: Phase II - Grade 3/4	4.8
Fever(no neutropenia): Phase I - Any Grade	8.3
Fever(no neutropenia): Phase I - Grade 3/4	0
Fever(no neutropenia): Phase II - Any Grade	19
Fever(no neutropenia): Phase II - Grade 3/4	4.8
Headache: Phase I - Any Grade	50
Headache: Phase I - Grade 3/4	0
Headache: Phase II - Any Grade	23.8
Headache: Phase II - Grade 3/4	0
Hypomagnesmia: Phase I - Any Grade	0
Hypomagnesmia: Phase I - Grade 3/4	0
Hypomagnesmia: Phase II - Any Grade	19
Hypomagnesmia: Phase II - Grade 3/4	4.8
Vomiting: Phase I - Any Grade	16.7
Vomiting: Phase I - Grade 3/4	0
Vomiting: Phase II - Any Grade	23.8
Vomiting: Phase II - Grade 3/4	4.8

SecondaryClinical Benefit Rate

Clinical Benefit Rate (CR + PR + SD lasting more than 90 days)

Time frame:: 12 months

No measurements were reported for this outcome.

Adverse events

Collected over Participants were monitored for adverse events for the duration of their participation in the trial, generally up to one year.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Pemetrexed + Cetuximab	—	11/36 (30.6%)	32/36 (88.9%)

Most frequent serious events

Showing 10 of 14

Most frequent serious events
Event	Pemetrexed + Cetuximab
DEATH NOT ASSOCIATED WITH CTCAE TERM / DISEASE PROGRESSION NOSGeneral disorders	2/36
DIZZINESSNervous system disorders	2/36
CNS CEREBROVASCULAR ISCHEMIANervous system disorders	1/36
DEHYDRATIONGastrointestinal disorders	1/36
DYSPNEA (SHORTNESS OF BREATH)Respiratory, thoracic and mediastinal disorders	1/36
HEMORRHAGE, PULMONARY/UPPER RESPIRATORY / LUNGRespiratory, thoracic and mediastinal disorders	1/36
INFECTION - OTHER (SPECIFY, __)Infections and infestations	1/36
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / BONE (OSTEOMYELITIS)Infections and infestations	1/36
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / LUNG (PNEUMONIA)Infections and infestations	1/36
MAGNESIUM, SERUM-LOW (HYPOMAGNESEMIA)Investigations	1/36

Most frequent other events

Showing 10 of 97

Most frequent other events
Event	Pemetrexed + Cetuximab
FATIGUE (ASTHENIA, LETHARGY, MALAISE)General disorders	21/36
RASH: ACNE/ACNEIFORMSkin and subcutaneous tissue disorders	18/36
ANOREXIAGastrointestinal disorders	13/36
DYSPNEA (SHORTNESS OF BREATH)Respiratory, thoracic and mediastinal disorders	12/36
COUGHRespiratory, thoracic and mediastinal disorders	11/36
MUCOSITIS/STOMATITIS (CLINICAL EXAM) / ORAL CAVITYSurgical and medical procedures	11/36
NAUSEAGastrointestinal disorders	10/36
PAIN / HEAD/HEADACHEGeneral disorders	9/36
DIARRHEAGastrointestinal disorders	8/36
HAIR LOSS/ALOPECIA (SCALP OR BODY)Skin and subcutaneous tissue disorders	8/36

Baseline characteristics

33 of 36 consented participants received treatment.

Age, Continuous
Age, Continuous(years)	Pemetrexed + Cetuximab
Median	64 (37 to 80)

Sex: Female, Male
Sex: Female, Male(Participants)	Pemetrexed + Cetuximab
Female	13
Male	20

Region of Enrollment
Region of Enrollment(participants)	Pemetrexed + Cetuximab
United States	33

Eastern Cooperative Oncology Group (ECOG) performance status
Eastern Cooperative Oncology Group (ECOG) performance status(participants)	Pemetrexed + Cetuximab
ECOG PS 0	19
ECOG PS 1	14

Disease Stage
Disease Stage(participants)	Pemetrexed + Cetuximab
Disease Stage III	2
Disease Stage IV	31

Tumor Histology
Tumor Histology(participants)	Pemetrexed + Cetuximab
Adenocarcinoma	18
Squamous cell carcinoma	8
Large cell carcinoma	2
Non-small cell carcinoma (NOS)	5

Smoking History
Smoking History(participants)	Pemetrexed + Cetuximab
Current Smoker	6
Former Smoker	24
Never a Smoker	3

Previous Treatment
Previous Treatment(participants)	Pemetrexed + Cetuximab
1 Chemotherapy	26
2 Chemotherapy	5
>2 Chemotherapy	2
Previous Targeted Therapy	6
Previous radiotherapy	14

Study locations

11 sites

Medical & Surgical Specialists, LLC
Galesburg, Illinois 61401, United States
Cancer Care Center of Southern Indiana
Bloomington, Indiana 47403, United States
Elkhart Clinic
Elkhart, Indiana 46515, United States
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana 46815, United States
Center for Cancer Care at Goshen Health System
Goshen, Indiana 46527, United States
Indiana University Cancer Center
Indianapolis, Indiana 46202, United States
Medical Consultants, P.C.
Muncie, Indiana 47303, United States
Northern Indiana Cancer Research Consortium
South Bend, Indiana 46601, United States
Greenebaum Cancer Center
Baltimore, Maryland 21201, United States
Oncology Hematology Care, Inc.
Cincinnati, Ohio 45242, United States
Texas Oncology Cancer Center
Austin, Texas 78731, United States

References and documents

Publications

Jalal S, Waterhouse D, Edelman MJ, Nattam S, Ansari R, Koneru K, Clark R, Richards A, Wu J, Yu M, Bottema B, White A, Hanna N. Pemetrexed plus cetuximab in patients with recurrent non-small cell lung cancer (NSCLC): a phase I/II study from the Hoosier Oncology Group. J Thorac Oncol. 2009 Nov;4(11):1420-4. doi: 10.1097/JTO.0b013e3181b624ae. PubMed 19701110 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 29, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00216203
Lead sponsor: Nasser Hanna, M.D.
Collaborators: Eli Lilly and Company, Bristol-Myers Squibb, Walther Cancer Institute
Responsible party: Nasser Hanna, M.D. (Sponsor-Investigator, Hoosier Cancer Research Network) — Sponsor-investigator
First posted: Sep 22, 2005
Start date: May 2005
Primary completion: Dec 2008
Completion: Dec 2008
Results posted: Jun 2, 2016
Last update: Sep 29, 2016

Study contacts

Nasser Hanna, M.D.

study chair · Hoosier Oncology Group, LLC

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2016. You cannot join it, but the record below documents what was studied.

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