Phase I Study Compound 451238 and Radiotherapy in Soft-tissue Sarcoma

NCT03602833 | Completed Phase 1 Results DMC

• 2 other identifiers: CCR 46402017-001316-11
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this trial is to assess the safety and tolerability of combining compound 451238 and radiotherapy, treating advanced STS.

Conditions

Soft-tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Count of Patients With Dose Limiting Toxicity

  To assess the safety and tolerability of combining radiotherapy with compound 451238(avelumab) as evidenced by the rate of occurrence of dose limiting toxicities assessed using CTCAE v4.0. .

  Dose limiting toxicity was assessed from first dose of avelumab in week 1, then weekly until and including week 7 and every other week thereafter until and including the 7th dose of avelumab at week 13

Secondary Outcomes (7)

• Evaluate Local Control (LC)

  3 months from end of radiotherapy

• Progression Free Survival (PFS)

  1 Year

• Overall Survival

  Start of treatment to 2 years

• Count of Patients by Worst Grade Acute Toxicity

  11 weeks

• Count of Patients by Worst Grade Late Toxicity

  From 13 weeks from start of treatment until 90 days after the end of treatment

Other Outcomes (2)

• Response Rate in Non-target Lesions

  3 months following first dose of trial treatment

• Overall Response by Immunological Biomarkers

  Best response within 6 months from commencing trial treatment

Study Arms (1)

Compound 451238

EXPERIMENTAL

To assess the safety and tolerability of combining radiotherapy with compound 451238, treating advanced STS.

Drug: Compound 451238

Interventions

Compound 451238 DRUG

Each patient will receive compound 451238 until disease progression unacceptable toxicities.

Compound 451238

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a diagnosis of soft tissue sarcoma with at least 2 metastases not suitable for cure using conventional treatments. At least one lesion must be suitable to receive palliative radiotherapy. The radiation tumour target volume must be between the neck and the diaphragm in the thorax, trunk of an extremity.
• Histological confirmed diagnosis of soft-tissue sarcoma .
• Age ≥ 18 years.
• Life expectancy of \> 12 weeks.
• At least one site of accessible disease of pre- and post-treatment core biopsies.
• At least two sites of measurable disease on CT
• ECOG Performance Status of ≤ 1.
• Adequate bone marrow function
• Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula.
• Adequate liver function.
• Written, voluntary informed consent.
• Patients may have received ≥ 1 or more lines systemic therapies. Women of childbearing potential (WOCBP) and male partners of WOCBP must agree to use 2 highly effective methods of contraception from giving informed consent for a period of 28 days prior to administration of first dose of compound 451238, throughout treatment with compound 451238 and for at least 60 days after treatment. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study as defined in section 7.3.7.
• Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study as defined in section 7.3.7. See CTFG Contraception Guidance 15.09.2015.
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
• Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.

You may not qualify if:

• Systemic chemotherapy within 28 days prior to study entry.
• Prior systemic therapy.
• Patients who are curable by conventional multidisciplinary management.
• Patients with known central nervous system metastatic disease are ineligible for enrollment.
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
• Patients who have received radiotherapy ≤ 4 weeks prior to Day 1 of study or who have not recovered adequately from side effects.
• Previous radiotherapy within the treatment area.
• Patients who have active infections requiring therapy.
• Patients with a history of Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C. Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive.
• Patients that have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
• Patients who received systemic anti-cancer treatment prior to the first dose of study drug within the following time frames:
• Patients who have received biologic therapy within 4 weeks.
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug
• Patients with active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients that require inhaled steroids or local steroid injections would not be excluded from the study. Patients with hypothyroidism not from autoimmune disease that is stable on hormone replacement will not be excluded from the study.
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). xvi. Active autoimmune disease that might deteriorate. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Angelie Tirona
• Organization: The Royal Marsden NHS Foundation Trust

apple.trial@rmh.nhs.uk

+44 20 8915 6788

Study Officials

• Shane Zaidi

  MRCP FRCR

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: July 27, 2018
• Study Start: November 5, 2018
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: March 2, 2026
• Results First Posted: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)