The purpose of this study is:
- To find out if the chemotherapy treatment using Pemetrexed (Alimta) and Oxaliplatin
(Eloxatin) given together will kill the cancer cells in the patient's body and shrink
the size of their tumor. This may allow patients to live longer or decrease the
frequency and/or severity of the symptoms caused by the cancer. Pemetrexed has been
approved by the Food and Drug Administration (FDA) to treat Lung Cancer. Oxaliplatin
has been approved by the FDA for the treatment of Colon Cancer. The combination of
these two drugs has been used to treat patients with Non-Small Cell Lung Cancer in
Italy but not yet in the USA
Other purposes of this study are:
- To better detail the toxic effects of this chemotherapy combination.
- To determine whether the level of specific gene and/or gene products (genes are genetic
material that allows cells to make proteins such as enzymes) are useful to predict if
this chemotherapy combination will work or not.
This is a non-randomized, two stage design, open-label Phase II trial in newly diagnosed
patients with advanced or metastatic NSCLC who have previously received and failed adjuvant
platinum-based chemotherapy for early stage, resected NSCLC.
Correlative Studies; Molecular correlative studies (genomic and proteomic) are included in
this protocol. Prior to chemotherapy, all patients will undergo a biopsy of the safest
and/or most accessible site of tumor in order to obtain tissue for mRNA measurements.
Additionally, patients will undergo blood sampling prior to the start of chemotherapy and
after 2 and 4 cycles of therapy in order to obtain plasma for the mass spectrometry
Patients, whose second and/or third specimen cannot be collected for any reason, will remain
in the trial, and treatment will continue as outlined in the protocol.
Expected Number of Patients:
The number of patients was calculated according to the procedure described in the Sample
Size Calculation section of the protocol. It is estimated that up to 50 patients will be
enrolled to obtain the 43 evaluable patients needed to meet the statistical design of the
Method of Treatment Allocation:
A patient number will be assigned sequentially to each patient upon registration. The
patient number and the patient initials are to be entered on each page of the Case Report
Duration of Study for Each Patient:
All patients will be treated with up to 6 cycles of chemotherapy. However, at the discretion
of the treating physician and principle investigator, patients may continue chemotherapy,
beyond 6 cycles, until disease progression, intolerable toxicity, or the development of any
study removal criteria. Patients will undergo an evaluation for extent of disease after
every other treatment cycle.
Patients will be considered to be on-study for the duration of their treatment and during
the 30 days following treatment discontinuation. Treatment discontinuation is defined as the
last day of study treatment. All included patients will be followed up until recovery or
stabilization of all adverse events or return to baseline condition. Patients who
discontinue from the trial prior to experiencing disease progression will be followed
monthly until demonstration of progressive disease.
The H. Lee Moffitt Cancer Center will conduct this trial through the Moffitt Clinical
Research Affiliate Network. Patients will be evaluated and the biopsy will be performed at
the H. Lee Moffitt Cancer Center. Since all the chemotherapeutic drugs used in the protocol
are FDA approved, and phase I and II safety data regarding this regimen has been
published30,31, the chemotherapy may be administered at the patients' primary (referring)
oncologists' office. Documentation of the administration of the chemotherapy will be
obtained for record keeping purposes.
- History of completely resected NSCLC and adjuvant/neoadjuvant chemotherapy with
- Histologically/cytologically confirmed recurrence of NSCLC after curative therapy
with surgery and adjuvant/neoadjuvant chemotherapy
- Must have measurable disease according to RECIST criteria
- ECOG Performance Score of 0-2 determined within 2 weeks prior to enrollment
- Expected survival > 12 weeks
- Adequate bone marrow function,as evidenced by:
1. Absolute neutrophil count (ANC) > 1,500/µL
2. Platelet count > 100,000/µL
3. Hemoglobin > 8 g/dL (determined within 2 weeks prior to enrollment)
- Adequate renal function evidenced by:
1. serum creatinine < 1.5 mg/dL OR
2. calculated creatinine clearance >45 mL/min.
- Adequate hepatic function evidenced by:
1. Serum total bilirubin < 1.5 mg/dL OR less than the upper limit of normal (ULN)
2. Alkaline phosphatase < 3X the ULN for the reference lab (< 5X the ULN for
patients with known hepatic or bony metastases)
3. SGOT/SGPT < 3X the ULN for the reference lab (< 5X the ULN for patients with
known hepatic metastases)
- Must be recovered from both acute and late effects of any prior surgery,
radiotherapy, other antineoplastic therapy
- Signed informed written consent
- Patients of childbearing potential and their partners must agree to use an effective
form of contraception during the study and for 90 days following last dose of study
- Patients amenable to a "curative intent" therapeutic approach (re-resection with or
without preoperative or postoperative therapy or chemoradiotherapy without surgery
are not eligible for this study).
- An active infection or with fever > 101.00 F within 3 days of first scheduled day of
- Active CNS metastases. Patients with stable CNS disease, who have undergone
radiotherapy (or surgery ± radiotherapy) at least 4 weeks prior to planned first
protocol treatment and who have been on stable or decreasing dose of corticosteroids
for >2 weeks are eligible
- Prior malignancy within the past 5 years except for curatively treated basal cell
carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate
cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations, at least 3
months apart, with most recent evaluation no more than 4 weeks prior to entry.
- Any diagnosis of NSCLC occurring after 5 years of curative therapy (surgery plus
adjuvant chemotherapy) for original NSCLC will be considered a second primary rather
than a recurrence and will render patient ineligible for this study. An exception
will be if both tumors are considered the same after a direct pathologic comparison
if both, sponsor and investigator agree.
- Patients that at discretion of the PI have a second primary rather than metastasis
are not eligible
- Known hypersensitivity to any of the components of oxaliplatin or pemetrexed.
- Patients receiving concurrent investigational therapy or who have received
investigational therapy within 30 days of the first scheduled day of protocol
- Patients who received radiotherapy to more than 33% of their bone marrow or received
any radiotherapy within 4 weeks of entry
- Peripheral neuropathy ≥ Grade 2
- Patients pregnant or lactating
- Any other medical condition, including mental illness or substance abuse, deemed
likely to interfere with patient's ability to sign informed consent, cooperate and
participate in the study, or interfere with interpretation of the results.
- History of allogeneic transplant
- Known history of HIV or Hepatitis B or C infection. Patients with Hepatitis B carrier
status only are eligible.