High-dose Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases

• ClinicalTrials.gov Identifier: NCT02284490
• Recruitment Status: Unknown
• First Posted: November 6, 2014
• Last Update Posted: November 6, 2014
• Sponsor: Rongjie Tao
• Collaborator: National Natural Science Foundation of China
• Information provided by (Responsible Party): Rongjie Tao, Shandong Cancer Hospital and Institute

Tracking Information

• First Submitted Date: October 10, 2014
• First Posted Date: November 6, 2014
• Last Update Posted Date: November 6, 2014
• Study Start Date: November 2014
• Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 3, 2014): Determine the 6-month progression-free survival rate in patients with brain metastases from lung adenocarcinoma treated with pemetrexed disodium. [ Time Frame: 1.5 years ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: November 3, 2014)

• Determine the radiographic response in patients with brain metastases from lung adenocarcinoma treated with pemetrexed disodium. [ Time Frame: 2 years ]
• Determine the time to response in patients treated with this drug. [ Time Frame: 2 years ]
• Determine the duration of response in patients treated with this drug. [ Time Frame: 2 years ]
• Determine the overall survival of patients treated with this drug. [ Time Frame: 2 years ]
• Collect safety data on patients with brain metastases from lung adenocarcinoma treated with this drug. [ Time Frame: 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High-dose Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases
• Official Title: High-dose Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases
• Brief Summary: This phase II trial is studying how well pemetrexed disodium works in treating patients with Lung Adenocarcinoma With Brain Metastases

Detailed Description

• Determine the 6-month progression-free survival rate in patients with Lung Adenocarcinoma With Brain Metastases treated with pemetrexed disodium.
• Determine the time to progression in patients with Lung Adenocarcinoma With Brain Metastases treated with pemetrexed disodium.

Secondary

• Determine the radiographic response in patients with Lung Adenocarcinoma With Brain Metastases treated with pemetrexed disodium.
• Determine the time to response in patients treated with this drug.
• Determine the duration of response in patients treated with this drug.
• Determine the overall survival of patients treated with this drug.
• Collect safety data on patients with intracranial tumors treated with this drug.

OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Brain Metastases

Intervention

Drug: pemetrexed

Administered intravenously at a dose of 900 mg/m2 every 21 days until disease progression.

Other Names:

• pemetrexed disodium
• Alimta

Study Arms

Experimental: Treatment Arm

Pemetrexed 900 mg/m² every 21 days until disease progression.

Intervention: Drug: pemetrexed

Publications *

• Bailon O, Chouahnia K, Augier A, Bouillet T, Billot S, Coman I, Ursu R, Belin C, Zelek L, Des Guetz G, Levy C, Carpentier AF, Morere JF. Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma. Neuro Oncol. 2012 Apr;14(4):491-5. doi: 10.1093/neuonc/nos004. Epub 2012 Feb 22.
• Ito S, Ogawa Y, Harada H, Yamaguchi T, Munakata K. [Long-term survival of patient with brain metastases from lung cancer treated by pemetrexed monotherapy]. Gan To Kagaku Ryoho. 2012 May;39(5):793-6. Japanese.
• Dinglin XX, Huang Y, Liu H, Zeng YD, Hou X, Chen LK. Pemetrexed and cisplatin combination with concurrent whole brain radiotherapy in patients with brain metastases of lung adenocarcinoma: a single-arm phase II clinical trial. J Neurooncol. 2013 May;112(3):461-6. doi: 10.1007/s11060-013-1079-5. Epub 2013 Feb 19.
• Zhuang H, Yuan Z, Wang J, Zhao L, Pang Q, Wang P. Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma. Drug Des Devel Ther. 2013 Oct 8;7:1179-86. doi: 10.2147/DDDT.S53011. eCollection 2013.
• Yang H, Yang X, Zhang Y, Liu X, Deng Q, Zhao M, Xu X, He J. Erlotinib in combination with pemetrexed/cisplatin for leptomeningeal metastases and cerebrospinal fluid drug concentrations in lung adenocarcinoma patients after gefitinib faliure. Target Oncol. 2015 Mar;10(1):135-40. doi: 10.1007/s11523-014-0326-9. Epub 2014 Jul 2.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 3, 2014): 25
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2017
• Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed brain metastases from lung adenocarcinoma.
• Measurable (greater than 1 cm in diameter) tumor by CT scan or MRI.
• ECOG (Eastern Cooperative Oncology Group) Performance status of 0-1.
• Measurable disease as defined by bidimensionally measurable lesions with clearly defined margins by CT scan or MRI.
• Biopsy is not required if radiographic imaging is consistent with brain metastases.
• Must have failed prior whole-brain radiotherapy.
• Patients with leptomeningeal metastases with or without brain metastases are eligible for therapy (may be diagnosed by MRI or cytology).
• Karnofsky performance score ≥ 60
• WBC > 3,000/mm^3
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 10 mg/dL (transfusion allowed)
• SGOT/SGPT < 3.0 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN
• Creatinine < 1.5 mg/dL
• Creatinine clearance > 45 mL/min
• Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study and for 3 months after completing study treatment
• Women who are pregnant or breast-feeding are not eligible for study treatment
• Negative pregnancy test
• Able to take steroids, vitamin B12, or folate
• No significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

Exclusion Criteria:

• Symptomatic brain metastasis
• Have received prior radiotherapy for brain metastasis
• Unable or unwilling to take folic acid, vitamin B12 supplementation or dexamethasone (or equivalent corticosteroid); or any other inability to comply with protocol or study related procedures.
• A prior malignancy other than NSCLC, except carcinoma in situ of the cervix or non-melanoma skin cancer, adequately treated low grade [Gleason score <6] localized prostate cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
• Serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete study.
• Inability to discontinue administration of aspirin at a dose >1.3g/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam).
• Presence of fluid accumulations in third spaces, e.g., ascite or pleural effusion, which can be detected clinically (during physical examination), and which cannot be adequately controlled by drainage or other procedures prior to inclusion in the study.
• Peripheral neuropathy > CTC Grade 2
• Patient compliance or geographic distance precluding adequate follow up.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 95 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02284490
• Other Study ID Numbers: ShandongCHI003; ShandongCHI ( Registry Identifier: ShandongCHI )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Rongjie Tao, Shandong Cancer Hospital and Institute
• Study Sponsor: Rongjie Tao
• Collaborators: National Natural Science Foundation of China
• Investigators: Not Provided
• PRS Account: Shandong Cancer Hospital and Institute
• Verification Date: November 2014