slow accrual

This phase II trial will evaluate phyto-therapy's, in the form of blueberry powder, synergistic effect on second-line therapy for non-small cell lung cancer (NSCLC). The proposition is that the addition of blueberry polyphenolics to routine docetaxel therapy will have a significant, positive effect in the response rate and overall survival.

This study is designed to evaluate the feasibility of using blueberry powder (rich in anthocyanidins) as an adjunct therapy with the conventional chemotherapy drug paclitaxel/docetaxel for treatment of NSCLC. The study is based on information from published studies in which blueberry anthocyanidins (bioflavonoids which give blueberries their color) have been shown to regulate a vast array of molecular targets, and on our own exciting and compelling preliminary data showing that blueberry anthocyanidins elicited potent synergistic chemo-sensitizing effects in two highly aggressive non-small cell lung cancer (NSCLC) cell lines.

Inclusion Criteria:

1. Provide written informed consent prior to screening

2. Male or female patients, age ≥ 18 years

3. Histologically or cytologically confirmed diagnosis of NSCLC

4. Stage IV disease (including patients with pleural effusion previously classified as Stage IIIB)

5. All of the following if patient has had prior radiation therapy:

   • lesion(s) used for determination of response were not previously irradiated or have increased in size since the completion of radiotherapy
   • the patient has recovered from any acute effects of the radiotherapy
   • radiotherapy was completed at least 4 weeks prior to screening

6. Part 1: Have at least non-measurable evaluable disease (e.g., lesions which are smaller than the minimum size required for measurability; other non-measurable lesions such as bone metastases, malignant pleural effusion)

7. Part 2: Have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as > 10 millimeters (mm) on cross-sectional imaging (where the CT slice thickness is no greater than 5 mm) or at least 20 mm by standard techniques; positron emissions tomography [PET] and ultrasound are not permitted methods for tumor measurements under this protocol.

8. Performance status of 0 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale

9. Have an estimated life expectancy of at least 12 weeks

10. Adequate organ function within 14 days prior to first berry powder dose or docetaxel whichever occurs first, including the following - absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L), patients may receive packed red blood cells (RBC) transfusion to achieve this level at the discretion of the investigator, total bilirubin < 1.5 x upper limit of normal (ULN) unless elevated secondary to conditions such as Gilbert's Disease, aspartate aminotransferase (AST) < 3 x ULN (< 5 x ULN in the presence of hepatic metastases), alanine aminotransferase (ALT) < 3 x ULN (< 5 x ULN in the presence of hepatic metastases), alkaline phosphatase < 3.0 x ULN, calculated creatinine clearance ≥ 60 mL/min per Cockcroft and Gault formula

11. Satisfy one of the following:

    • Females: non-pregnant and non-lactating; surgically sterile, post-menopausal, or patient/partner compliant with a reliable contraceptive regimen, as determined by the Investigator, for 4 weeks prior to screening. Patients of reproductive potential must test negative for pregnancy at screening and must agree to use a reliable method of birth control during the study period
    • Males: surgically sterile or patient/partner must agree to use a reliable contraceptive method, as determined by the Investigator, during the study period
    • The patient is willing and able to comply with the study visit schedule and procedures, and has geographical proximity (Investigator's discretion) that allows follow-up specified by the protocol
    • For Part 1: have discontinued all prior chemotherapies, biological therapies, and other investigational therapies for cancer for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study treatment and have recovered from the acute effects of therapy

Exclusion Criteria:

1. Part 1: More than one prior chemotherapy (single biological therapy, i.e., Erlotinib not included) regimens (approved or experimental) for NSCLC, not counting adjuvant and neoadjuvant treatment. A regimen is defined as two or more consecutive cycles of treatment. Part 2: Any prior chemotherapy or biological therapy (approved or experimental) for NSCLC including adjuvant and neoadjuvant treatments
2. Treatment with another investigational drug, biological agent, or device within 4 weeks (6 weeks for biological agents) before screening or 5 half-lives of study agent, whichever is longer
3. Patients with treated or untreated parenchymal brain metastases or leptomeningeal disease. Brain imaging is required for symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients
4. Patients with known pericardial effusion
5. Patients with active infection or serious concomitant systemic disorder (for example, heart failure) incompatible with the study (at the discretion of the Investigator)
6. Presence or history of malignancy other than NSCLC, carcinoma in situ of the cervix, or non-melanoma skin cancer. In the case of other malignancies, patients may be considered for participation if the prior malignancies were diagnosed and definitively treated at least two years previously with no subsequent evidence of recurrence.
7. Presence of an underlying disease state associated with active bleeding
8. Concurrent treatment with other anticancer drugs
9. Pre-existing peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE) Grade 2
10. Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device
11. Patients with any other medical conditions that in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study
12. Allergy to berries