M3541 in Combination With Radiotherapy in Solid Tumors

NCT ID: NCT03225105

Last Updated: 2023-11-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-06

Study Completion Date

2020-04-27

Brief Summary

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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.

Detailed Description

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Conditions

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Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Subsequent cohorts of patients treated at different dose levels.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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M3541 50 mg + RT

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).

Group Type EXPERIMENTAL

M3541

Intervention Type DRUG

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).

Palliative Radiotherapy (RT)

Intervention Type RADIATION

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).

M3541 100 mg + RT

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).

Group Type EXPERIMENTAL

M3541

Intervention Type DRUG

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).

Palliative Radiotherapy (RT)

Intervention Type RADIATION

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).

M3541 200 mg + RT

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).

Group Type EXPERIMENTAL

M3541

Intervention Type DRUG

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).

Palliative Radiotherapy (RT)

Intervention Type RADIATION

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).

M3541 300 mg + RT

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).

Group Type EXPERIMENTAL

M3541

Intervention Type DRUG

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).

Palliative Radiotherapy (RT)

Intervention Type RADIATION

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).

Interventions

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M3541

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).

Intervention Type DRUG

Palliative Radiotherapy (RT)

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).

Intervention Type RADIATION

Eligibility Criteria

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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)

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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

Locations

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IU Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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Waqar SN, Robinson C, Olszanski AJ, Spira A, Hackmaster M, Lucas L, Sponton L, Jin H, Hering U, Cronier D, Grinberg M, Seithel-Keuth A, Diaz-Padilla I, Berlin J. Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors. Invest New Drugs. 2022 Jun;40(3):596-605. doi: 10.1007/s10637-022-01216-8. Epub 2022 Feb 12.

Reference Type DERIVED
PMID: 35150356 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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MS200770_0001

Identifier Type: -

Identifier Source: org_study_id