This is an open label trial to assess the efficacy of MBM-02 (Tempol) as a treatment for
patients diagnosed with prostate cancer in biochemical recurrence.
Preliminary data shows MBM-02 has anti-prostate cancer activity without hormone suppression
or toxicity to non-cancerous cells and organs.
Solid tumors contain hypoxic regions (low oxygen) due to their high rates of cell
proliferation and formation of aberrant blood vessels. Intratumoral hypoxia is associated
with increased risk of invasion, metastasis, and patient mortality. Cancer cells respond to
hypoxia by stabilizing hypoxia-inducible factor 1 (HIF-1) and hypoxia inducible factor 2
(HIF-2). HIF-1 and HIF-2 activate a transcription of genes encoding proteins that mediate
major adaptive responses to hypoxia that are critical for cancer cell survival. Without
activation of HIF-1 and HIF-2, cancer cells would not survive.
MBM-02 has been shown to inhibit the genes responsible for prostate carcinogenesis, HIF-1 and
HIF-2.
This trial is an open label study that will employ a 3+3 escalation design up to 1600 mg/day.
Patients will be exposed to study drug for 20 weeks. PSA and scans will be taken at baseline
and week 20 for efficacy.
Inclusion Criteria:
1. Male 18 years or older;
2. Histologically or cytologically confirmed diagnosis of prostate cancer;
3. Patient must have had previous treatment with definitive surgery or radiation therapy,
cryoablation, or brachytherapy;
4. Patient may have prior salvage therapy (surgery, radiation or other local ablative
procedures) within 6 months prior to randomization if the intent was for cure.
Prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to
randomization is allowed
5. Patient must have evidence of biochemical failure after primary therapy and subsequent
progression. Biochemical failure is declared when the PSA reaches a threshold value
after primary treatment and it differs for radical prostatectomy or radiation therapy:
1. For radical prostatectomy the threshold for this study is PSA ≥ 0.8ng/mL
2. For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA
achieved post radiation with or without hormone therapy (2006 RTOG-ASTRO
Consensus definition).
6. PSA progression requires a PSA rise above the threshold measured at any time point
since the threshold was reached;
7. PSA doubling time ≤ 12 months. PSA calculation requires two consecutive PSA rises
(PSA2 and PSA3) above the threshold PSA (total 3 PSA values); PSA2 and PSA3 must be
obtained within 12 months of study entry. All baseline PSAs should be obtained at the
same reference lab.
8. ECOG performance status less than or equal to 2;
9. Ability to swallow the study drugs;
10. If a male with a female partner of child bearing potential, adequate methods of
contraception must be employed;
11. If male, no sperm donation for 90 days until after the conclusion of the study;
12. Be properly informed of the nature and risks of the clinical investigation, comply
with all clinical investigation-related procedures, and sign an Informed Consent Form
prior to entering the clinical investigation;
13. Be able to participate for the full term of the clinical investigation;
14. Have a Karnofsky performance status of >70;
15. Have a life expectancy ≥ 6 months; and
16. Have adequate baseline organ function (hematologic, liver, renal, nutritional and
metabolic):
Hematology:
Absolute neutrophil count (ANC) ≥1.5 Hemoglobin ≥ 10 g/dL Platelets ≥ 100,000 per
microliter of blood
Hepatic:
Total bilirubin ≤ 2 x ULN Alanine aminotransferase (ALT) and Aspartate aminotransferase
(AST) ≤2.5 x ULN
Renal:
creatinine clearance (CrCl) ≥ 60 ml/min within 2 weeks prior to registration determined by
24-hour collection or estimated by Cockcroft-Gault formula: CrCl male = [(140 - age) x (wt
in kg)] [(Serum Cr mg/dl) x (72)] CrCl female = 0.85 x (CrCl male)
Exclusion Criteria:
1. Evidence of metastatic disease on imaging studies (CT and/or bone scan);
2. Diagnosis of diabetes mellitus defined as:
1. Fasting blood glucose > 126 mg/dl or,
2. Random blood glucose > 200 mg/dl
3. Hemoglobin A1C > 6.5%
3. Patients with QTc >480 msec
4. Need for treatment with any conventional modality for prostate cancer (surgery,
radiation therapy, and hormonal therapy);
5. Treatment within the last 30 days with any investigational drug;
6. Radiation therapy within prior 6 months (prophylactic radiotherapy to prevent
gynecomastia within 4 weeks prior to randomization is allowed);
7. Patient with previous or concurrent malignancy. Exceptions are made for patients who
meet any of the following conditions: Basal cell or squamous cell carcinoma of the
skin or prior malignancy that has been adequately treated and patient has been
continuously disease free for ≥ 2 years;
8. Evidence of a significant medical illness, or a psychiatric illness/social situation
that would, in the investigator's judgment, make the patient inappropriate for this
study;
9. Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel
resection that would preclude adequate absorption of the study drug;
10. Have had a recent, serious, non-malignant medical complication that, in the opinion of
the investigator, makes the individual unsuitable for study participation;
11. Have used an investigational drug within 28 days of the initiation of study treatment;
12. Have a history of a positive blood test for HIV;
13. At the time of screening, have a significant active medical illness which, in the
opinion of the investigator, would preclude completion of the study; and
14. Body weight less than 35 kg (77 lbs.)
