A Phase I Dose-escalation Study of Subcutaneous ALM201 in Patients With Advanced Ovarian Cancer and Other Solid Tumours
Condition: Solid Tumors; Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: ALM201
Intervention description: Drug: ALM201 administered subcutaneously
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

Summary:

      ALM201/0001 is a Phase I, open-label, dose-escalation study of the safety, tolerability and
      pharmacokinetics (PK) of ALM201.

      Part 1 will be a dose-escalation study. Patients with advanced solid tumours will receive
      daily doses of ALM201 on Days 1-5, 8-12 and 15-19 in 21 day cycles.

      Part 2 will be a dose-expansion of the Maximum Tolerated Dose (MTD) determined in Part 1.
      Patients with advanced ovarian cancer will be enrolled with the main objective to determine
      the recommended Phase II dose.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Part 1 Specific Inclusion Criterion

             *Patients with histologically and/or cytologically confirmed advanced solid tumour for
             whom no standard effective therapy is available or felt likely to be of limited
             efficacy and in whom a rationale for use of an anti-angiogenic treatment approach
             exists. Note: Previous use of anti-angiogenic therapy is allowed if tolerated

          -  Part 2 Specific Inclusion Criterion

             *Patients with advanced ovarian cancer, who are intolerant of or whose tumour is
             resistant to platinums and who have failed to respond to, or have relapsed following,
             standard therapy and whose tumour has a proangiogenic profile as assessed by the
             angiogenesis gene signature test. Note: Previous use of anti-angiogenic therapy is
             allowed if tolerated.

          -  General Inclusion Criteria for all Patients

               -  Measurable or evaluable disease.

               -  Recovery from previous treatment to baseline or CTCAE ≤ Grade 1, as determined by
                  CTCAE v4.03 criteria (Appendix B), of reversible toxicities related to prior
                  treatment, with the exception of alopecia, lymphopenia, other non-clinically
                  significant adverse events; recovery from previous radiotherapy other than
                  residual cutaneous effects or stable < Grade 2 gastrointestinal toxicity;
                  complete recovery from surgery other than stable < Grade 2 toxicity.

               -  ECOG Performance Status (PS) of 0 or 1.

               -  Acceptable haematological, renal and hepatic

               -  Women must have either a negative pregnancy test prior to first study drug
                  administration or be post menopausal. Male and female patients of childbearing
                  potential must use appropriate methods birth control.

               -  Patients must give written informed consent and understand the requirements of
                  the study

        Exclusion Criteria:

        For all Patients

          -  History of inability to tolerate anti-angiogenic therapies e.g. increased blood
             pressure (BP), proteinuria, prior thromboembolic events.

          -  Previous history of bowel obstruction, clinical evidence of gastro-intestinal
             obstruction, large burden of peritoneal disease or evidence of bowel involvement on
             computed tomography.

          -  Patents has received:

               -  any chemotherapy regimens (including investigational agents) with delayed
                  toxicity within 4 weeks (6 weeks for prior nitrosourea or mitomycin C) of Cycle
                  1, Day 1, or received chemotherapy regimens given continuously or on a weekly
                  basis which have limited potential for delayed toxicity within 2 weeks of Cycle
                  1, Day 1.

               -  radiotherapy, immunotherapy or biological agents (includes investigational
                  agents) within 4 weeks of Cycle 1, Day 1. Localised palliative radiotherapy is
                  permitted for symptom control.

          -  Documented, symptomatic or uncontrolled intracranial metastases or primary
             intracerebral tumours.

          -  Cancer with leptomeningeal involvement.

          -  On therapeutic anti-coagulation (aspirin dosing ≤100 mg per oral (PO) daily allowed).

          -  Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ
             of the uterine cervix, unless the tumour was treated with curative intent more than 2
             years prior to study entry.

          -  Active cardiac condition or history of significant cardiac condition. Known human
             immunodeficiency virus positivity.

          -  Active hepatitis B or C or other active liver disease (other than malignancy).

          -  Any active, clinically significant, viral, bacterial, or systemic fungal infection
             within 4 weeks prior to Cycle 1, Day 1.

          -  Any evidence of severe or uncontrolled systemic conditions or any other issues which
             make it undesirable for the patient to participate in the study or which could
             jeopardize compliance with the protocol.