M3541 in Combination With Radiotherapy in Solid Tumors

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 1

Conditions: Solid Tumors

Treatments: Radiation: Palliative Radiotherapy (RT); Drug: M3541

Study type: Interventional

Funder types: Industry

Identifiers

NCT03225105

MS200770_0001

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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15 participants in 4 patient groups

M3541 50 mg + RT

Experimental group

Description:

Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).

Treatment:

Drug: M3541

Radiation: Palliative Radiotherapy (RT)

M3541 100 mg + RT

Experimental group

Description:

Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).

Treatment:

Drug: M3541

Radiation: Palliative Radiotherapy (RT)

M3541 200 mg + RT

Experimental group

Description:

Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).

Treatment:

Drug: M3541

Radiation: Palliative Radiotherapy (RT)

M3541 300 mg + RT

Experimental group

Description:

Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).

Treatment:

Drug: M3541

Radiation: Palliative Radiotherapy (RT)