M3541 in Combination With Radiotherapy in Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: M3541; Palliative Radiotherapy (RT)
Intervention description: Participants received M3541 orally once per fraction day (FD) for two consecutive calendar weeks (that is, Monday through Friday, with Saturday and Sunday as M3541 holidays).; Participants received RT dose of 30 Gray (Gy) given in 10 fractions (3 Gy given per fraction day) administered over two consecutive calendar weeks (that is, Monday through Friday, with Saturday and Sunday as RT holidays).
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Subsequent cohorts of patients treated at different dose levels.
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Solid Tumors; M3541; Palliative radiotherapy; Adenosine triphosphate-competitive inhibitor

Summary:

      This dose-escalation study evaluated the safety, tolerability, pharmacokinetic (PK),
      pharmacodynamic, and explore antitumor activity of M3541 in combination with fractionated
      palliative radiotherapy (RT) in participants with solid tumors with malignant lesions in the
      thorax, abdominal cavity, head and neck region, or extremities likely to benefit from
      palliative RT.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have solid tumors with malignant lesions in the thorax, abdominal
             cavity, head and neck region, or extremities (any histology) likely to benefit from
             palliative radiotherapy; participants requiring palliative RT for lesions in the spine
             or lesions adjacent to the spinal cord are excluded from this study

          -  Eastern Cooperative Oncology Group performance status (ECOG PS) =< 2

          -  Life expectancy >= 3 months

          -  Adequate hematologic, hepatic, and renal function

          -  Agree to use highly effective contraception (that is, methods with a failure rate of
             less than 1 percent per year) if the participant is male or a female of childbearing
             potential (female partners of childbearing potential of male participants must also
             agree to use highly effective contraception)

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Use of other anticancer therapy within 15 days before the first dose of M3541
             administration and should not be within the "at risk follow-up period" for that
             specific anticancer therapy. The use of any investigational agent is not allowed
             within 28 days before the first dose of M3541

          -  Residual toxicity due to previous anticancer therapy with no return to baseline or =<
             Grade 1 (except alopecia) according to Common Terminology Criteria for Adverse Events
             (CTCAE) v4.03

          -  Extensive prior RT on more than 30 percent of bone marrow reserves (by Investigator
             judgment), or prior bone marrow/stem cell transplantation within 5 years before study
             start

          -  Prior RT to the same region that would be irradiated in this study

          -  Participants at increased risk for radiation toxicities, such as known collagen
             vascular disease (example, scleroderma, Sjogren's disease, etc) or other inherited
             radiation hypersensitivity syndromes (example, Gorlin syndrome, Fanconi anemia,
             ataxia-telangiectasia, etc.)

          -  Surgical intervention within 28 days prior to the first dose of M3541 administration

          -  Known central nervous system metastases causing clinical symptoms or metastases that
             require therapeutic intervention. Participants with a history of treated central
             nervous system (CNS) metastases (by surgery or radiation therapy) are not eligible
             unless they have fully recovered from treatment, demonstrated no progression for at
             least 2 months, and do not require continued steroid therapy. Participants with CNS
             metastases incidentally detected during Screening that do not cause clinical symptoms
             and for which standard of care suggests no therapeutic intervention is indicated,
             should be discussed with the Sponsor Medical Responsible

          -  Active difficulty swallowing, malabsorption or other chronic gastrointestinal disease
             or conditions (including pancreas deficiency requiring Creon therapy) that may hamper
             compliance and/or absorption of M3541

          -  Participants currently receiving or unable to stop using medications or herbal
             supplements known to be potent inhibitors of cytochrome P450 (CYP) 3A and / or
             P-glycoprotein (P-gp) (CYP and / P-gp must stop at least 1 week before treatment with
             M3541) or potent inducers of CYP3A or P-gp (must stop at least 3 weeks before
             treatment with M3541) or drugs mainly metabolized by CYP3A with a narrow therapeutic
             index (must stop at least 1 day prior).

          -  Other protocol defined exclusion criteria could apply