M10-440 A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Evaluating the Efficacy of ABT-888 in Combination with Temozolomide Versus Temozolomide Alone in Subjects with Metastatic Melanoma. Lead PI - Professor Peter Hersey, Newcastle Melanoma Unit Contact person: Dr Pauline Hanrahan, Newcastle Melanoma Unit phone: 02 4985 0179 or Julie Coffey or Jin Og Sagong, Sydney Cancer Centre phone: 02 9515 7706
PI - A/Professor A. Hamilton, Sydney Cancer Centre
Inclusion Criteria
1. Subject must be ≥ 18 years of age
2. Histologically (or cytologically) confirmed metastatic melanoma
3. Unresectable Stage III or Stage IV metastatic melanoma
4. Subject has measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST
5. Subjects with no brain metastases or a history of previously treated brain metastases who:
- have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior to enrollment; and
- have a baseline MRI that shows no evidence of active intercranial disease; and have not had treatment with steroids within 1 week of study enrollment are eligible.
6. At least 28 days since prior anti-cancer therapy
7. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1
8. Subject must have adequate hematologic, renal and hepatic function as follows:
- Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5 × 109/L);
Platelets ≥ 100,000/mm3 (100 × 109/L); Hemoglobin ≥ 10.0 g/dL (1.4 mmol/L) - Renal function: Serum creatinine ≤ 1.5 × upper normal limit of institution's
normal range OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with
creatinine levels above institutional normal - Hepatic function: AST and/or ALT ≤ 2.5 × the upper normal limit of
institution's normal range. For subjects with liver metastases, AST and/or
ALT < 5 × the upper normal limit of institution's normal range; LDH≤ 2.0 × ULN;
bilirubin ≤ 1.5 × the upper normal limit of institution's normal range.
Subjects with Gilbert's Syndrome may have a bilirubin ≥ 1.5 × the
upper normal limit of institution's normal range. - Sodium levels must be between 130 mmol/L and 150 mmol/L
- Calcium levels must be between 8.00 mg/dL and 11.5 mg/dL.
9. Partial Thromboplastin Time (PTT) must be ≤ 1.5 × upper normal limit of institution's normal range and INR (International Normalized Ratio) < 1.5.
Subjects on anticoagulant (such as coumadin) will have PTT and INR as determined by the investigator.
10. Subject's with significant fluid retention, including ascites or pleural effusion, may be allowed at the discretion of the PI.
11. Life expectancy > 12 weeks.
12. Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below) prior to study entry, for the
duration of study participation and for 90 days following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test
within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Total abstinence from sexual intercourse (minimum one complete menstrual cycle)
- Vasectomized male subjects or vasectomized partner of female subjects
- Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
- Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
- IUD (Intra-Uterine Device)
- Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the
duration of the study and for 90 days following completion of therapy.
13. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
Exclusion Criteria
1. LDH > 2 × ULN.
2. Subjects with ocular malignant melanoma (all other melanoma subtypes are allowed).
3. A subject with a history of CNS metastases or leptomeningeal disease who does not meet the criteria outlined in inclusion criteria 5 is not eligible to participate.
4. Prior therapy with regimens containing DTIC or TMZ are excluded.
5. The subject has received prior DNA damaging agents or cytotoxic chemotherapy (prior therapies with biologic agents including IL-2, interferon, vaccines,
immunostimulants and signal transduction inhibitors are allowed).
6. Prior treatment with Whole Brain Radiation Therapy (WBRT).
7. The subject has received an investigational agent within 28 days prior to study drug administration.
8. Subjects with a history of seizure disorder and/or subjects currently receiving medications for seizure disorders (e.g., steroid or enzyme-inducing anticonvulsant drugs [EIACD's]).
9. The subject has had another active malignancy within the past five years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma
carcinoma of the skin. Questions regarding the inclusion of individual subjects should be directed to the Abbott Medical Monitor.
10. Clinically significant and uncontrolled major medical condition(s) including but not limited to:
- active uncontrolled infection,
- symptomatic congestive heart failure,
- unstable angina pectoris or cardiac arrhythmia,
- psychiatric illness/social situation that would limit compliance with study requirements.
11. Any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities.
12. Lactating or pregnant female.
