Phase I Study of KPT330 in Asian Patients

Inclusion Criteria:

* All patients must sign an informed consent in accordance with local institutional guidelines
* Age ≥ 21
* Dose Escalation Phase: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have radiological evidence of progressive disease on study entry that is deemed unlikely to benefit from further conventional therapy, or for which no standard therapy is available.

Dose Expansion Phase: Patients with previously treated, metastatic or advanced recurrent malignancy (including gastric, colorectal, lung, head and neck and gynaecological malignancies) which has been confirmed histologically or cytologically, and who have evidence of progressive disease on study entry that is deemed unlikely to benefit from further conventional therapy, or for which no standard therapy is available. Depending on the total number of patients enrolled in the dose escalation phase, the number of patients recruited in the subsequent dose expansion phase may be adjusted accordingly.

There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimens.

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 1;
* Patients must have adequate bone marrow function and organ function within 2 weeks of study treatment;

  1. Adequate hematologic function defined as:

     * platelets ≥ 125 x 109/L in dose escalation phase, and platelets ≥ 100 x 10(9)/L in dose expansion phase.
     * hemoglobin ≥ 5.59 mmol/L or 9 g/dL,
     * ANC ≥ 1.5 x 109/L,
     * WBC ≥ 3.0 x 109/L.
     * Up to 5% deviation is tolerated. Transfusions and growth factors are allowed prior to and throughout the study.
  2. Hepatic function: bilirubin \< 2.0 times the upper limit of normal (ULN), ALT \< 2.5 times ULN

     * Up to 10% deviation is acceptable
  3. Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault: (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.
  4. Amylase and lipase ≤ 1.5 x ULN;
  5. Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer);
  6. International normalization ratio (INR) (if not on anticoagulation therapy) and partial thromboplastin time (PTT) ≤ 1.5 x ULN;
* All patients (male and female) of childbearing potential must agree to use adequate birth control (barrier methods) during and for 3 months after participation in this study. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.

Exclusion Criteria:

* Patients with significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy;
* Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) ≤ 3 weeks prior to cycle 1 day 1
* Chemotherapy, or immunotherapy or any other systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1.
* Unstable cardiovascular function;
* Uncontrolled active infection (Hepatitis B and C infection are NOT exclusion criteria).
* Known HIV infection;
* Renal failure requiring haemodialysis or peritoneal dialysis;
* Clinically unstable, active infection requiring systemic antibiotics;
* Patients who are pregnant or breast-feeding;
* Concurrent cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years;
* Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications;
* Patients with serious psychiatric or medical conditions that could interfere with treatment.
* History of organ allograft within a period of 6 months or less prior to commencing study
* Concurrent therapy with approved or investigational anticancer therapeutics;
* Body weight significantly below ideal body weight in the opinion of the investigator
* Significant episode of bleeding in the last 4 weeks (e.g. hemorrhoids, epistaxis etc.)