Evaluation of Safety and Feasibility of OGX-011 in Combination With 2nd-line Chemotherapy in Patients With HRPC
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: custirsen (OGX-011)/mitoxantrone; custirsen (OGX-011)/docetaxel
Intervention description: All subjects began treatment with oral prednisone (5 mg twice daily, 10 mg/day) continued through completion of the final treatment cycle. Three IV administrations of OGX-011 (640 mg) were given as 2 hr infusions during the loading dose period (Days-9 to-1). Subjects were premedicated with either ibuprofen (400 mg) or acetaminophen (650 mg) 30 to 60 minutes prior to and every 4-6 hours for 24 hours following each of the three doses of OGX-011 during the loading dose period only. After the loading dose period, OGX-011 was given weekly on Days 1, 8, and 15 of each 21-day cycle.
Mitoxantrone was administered IV on Day 1 of each cycle at a planned dose of 12 mg/m² infused over 30 minutes.
Patients could receive a maximum of 9 cycles of treatment.; All subjects began treatment with oral prednisone (5 mg twice daily, 10 mg/day) continued through completion of the final treatment cycle. Three IV administrations of OGX-011 (640 mg) were given as 2 hr infusions during the loading dose period (Days-9 to -1). Subjects were premedicated with either ibuprofen (400 mg) or acetaminophen (650 mg) 30 to 60 minutes prior to and every 4-6 hours for 24 hours following each of the three doses of OGX-011 during the loading dose period only. After the loading dose period, OGX-011 was given weekly on Days 1, 8, and 15 of each 21 day cycle.
Docetaxel was administered IV on Day 1 of each cycle at a planned dose of 75 mg/m² infused over 60 minutes.
Patients could receive a maximum of 9 cycles of treatment.
Intervention MeSH terms: Docetaxel; Mitoxantrone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic hormone refractory prostate cancer (HRPC)

Summary:

      This study is for patients with cancer of the prostate gland that has metastasized or spread
      outside the prostate to other parts of the body. Patients have already been treated with a
      drug called docetaxel or Taxotere® (with or without the addition of a steroid called
      prednisone) some time in the recent past. They either did not respond to this therapy or
      responded to this therapy, but now the cancer is progressing (growing larger or has spread to
      other areas of the body).

      Custirsen (OGX-011) is an experimental drug that has been shown to increase the effectiveness
      of chemotherapy in several kinds of tumors, including prostate cancer.

      Both docetaxel and mitoxantrone have anticancer activity in prostate and are approved by
      Health Canada and the Food and Drug Administration for the treatment of patients with
      prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18 years

          2. Histologic diagnosis of adenocarcinoma of the prostate.

          3. Metastatic disease on chest X-ray, bone scan, or computed tomography (CT) scan.

          4. Failed after receiving a minimum of two cycles of a docetaxel based first line therapy
             regimen. Failure is defined as disease progression within 6 months of discontinuing
             first line docetaxel therapy. Disease progression is defined as one or more of the
             following:

               -  Progressive measurable (target) disease (by Response Evaluation Criteria in Solid
                  Tumors [RECIST] criteria): at least a 20% increase in the sum of the longest
                  diameters of measurable lesions (organ masses or lymph nodes) over the smallest
                  sum observed (baseline or nadir) or the appearance of one or more new lesions as
                  assessed by CT scan or chest X-ray.

               -  Bone scan progression: one or more new lesions on bone scan while on or following
                  docetaxel treatment.

               -  Increasing serum PSA level: rise in PSA on three consecutive measurements
                  obtained at least one week apart. If the third PSA value is less than the second,
                  an additional fourth test to confirm a rising PSA will be acceptable.

          5. Baseline laboratory values as stated below:

               -  Creatinine ≤ 1.5 x upper limit of normal (ULN)

               -  Bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's
                  disease)

               -  SGOT (AST) ≤ 1.5 x ULN

               -  Castrate serum testosterone level (< 50 ng/mL-or-< 1.7 mmol/L).

          6. If not treated with bilateral orchiectomy, patients must be willing to continue
             luteinizing hormone releasing hormone analogues throughout the study.

          7. Adequate bone marrow function defined as absolute neutrophil count (ANC) ≥ 1.5 x 10^9
             cells/L and platelet count ≥ 100 x 10^9/L.

          8. Karnofsky score ≥ 60

          9. Received no other chemotherapy, radioisotope therapy, strontium 89, or samarium 153.
             (Prior radiotherapy and steroids following first line docetaxel therapy are allowed.)

         10. Received no more than one prior biological response modifier therapy following first
             line docetaxel therapy.

         11. At least 21 days since completing the last dose of docetaxel, biological response
             modifier, and/or radiotherapy. (Exception for radiotherapy: at least 7 days since
             completing a single fraction of ≤ 800 cGy to a restricted field.)

         12. Has recovered from all therapy related toxicity to ≤ grade 2, (except alopecia and
             anemia.)

         13. Willing and able to give informed consent and follow protocol requirements.

        Exclusion Criteria:

          1. Life expectancy less than 12 weeks.

          2. Patient is beyond 6 months following the last dose of docetaxel.

          3. Patient could not tolerate a dose of docetaxel of at least 45 mg/m² at the end of
             first line therapy due to toxicity.

          4. History of or current documented brain metastasis or carcinomatous meningitis, treated
             or untreated. (Brain imaging in asymptomatic patients is not required.)

          5. Current symptomatic cord compression requiring surgery or radiation therapy. (Once
             treated, patients are eligible for the study.)

          6. Active second malignancy (except non melanomatous skin or superficial bladder cancer).

          7. Prior radiotherapy to > 25% of the bone marrow.

          8. Uncontrolled medical conditions such as a major active infection, myocardial
             infarction or stroke within 3 months, uncontrolled hypertension, and/or significant
             concurrent medical illness, that, in the opinion of the Investigator, would preclude
             protocol therapy.

          9. History of or active congestive heart failure.

         10. Known allergy or hypersensitivity to docetaxel or polysorbate 80 (diluent).