Purpose

The main purpose of the study was to define maximum tolerated dose (MTD), recommended Phase II dose (RP2D) safety and tolerability of Peposertib in combination with capecitabine and radiotherapy (RT).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Participants who have an Eastern Cooperative Oncology Group Performance Status less than or equals to (<=) 1 - Participants who have histologically confirmed and localized resectable rectal cancer (Stage 3) - Participants who received induction chemotherapy are allowed to be enrolled to this study except this induction is resulting in clinical complete response (cCR) or tumor progression - Participants who have lower edge of the tumor located in rectum - Adequate hematological, hepatic and renal function as defined in the protocol - Male participants if they agree to the following during the study intervention period and for at least 12 weeks after the last dose of study intervention - Female participants are eligible if not pregnant or breastfeeding - Other protocol defined inclusion criteria could apply

Exclusion Criteria

  • Participants with history of any other significant medical disease or psychiatric conditions that might in the assessment of the Investigator preclude safe participation in the study - Participants with history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study intervention - Unstable cardiovascular function within 6 months prior to enrollment - Hypertension uncontrolled by medication (ie, systolic blood pressure >= 150 millimeter of mercury (mmHg) and diastolic blood pressure >= 90 mmHg) - Participants with history of other malignant disease within the past 5 years, other than successfully treated basal carcinoma of the skin or carcinoma in situ of the cervix - Participants with known human immunodeficiency virus positivity, known active hepatitis (for example, hepatitis B virus or hepatitis C virus), current alcohol abuse, or cirrhosis - Participants with ongoing active infection or treatment with a live attenuated vaccine within 4 weeks of dosing - Participants with concomitant use of H2-blocker or proton pump inhibitors (PPIs) (or unable to stop at least 5 days prior to the first treatment). Note that calcium carbonate is acceptable - Participation in any interventional clinical study within 28 days prior to Screening or during participation in this study - Other protocol defined exclusion criteria could apply.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Peposertib 50 mg + RT + Capecitabine
Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
  • Drug: Peposertib 50 mg
    Participants received peposertib 50 milligram (mg) once daily 5 days per week up to 5.5 weeks.
    Other names:
    • M3814
    • MSC2490484A
  • Drug: Capecitabine
    Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.
  • Radiation: Radiotherapy (RT)
    Participants received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.
Experimental
Peposertib 100 mg + RT + Capecitabine
Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
  • Drug: Peposertib 100 mg
    Participants received peposertib 100 mg once daily 5 days per week up to 5.5 weeks.
  • Drug: Capecitabine
    Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.
  • Radiation: Radiotherapy (RT)
    Participants received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.
Experimental
Peposertib 150 mg + RT + Capecitabine
Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
  • Drug: Peposertib 150 mg
    Participants received peposertib 150 mg once daily 5 days per week up to 5.5 weeks.
  • Drug: Capecitabine
    Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.
  • Radiation: Radiotherapy (RT)
    Participants received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.
Experimental
Peposertib 250 mg + RT + Capecitabine
Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
  • Drug: Peposertib 250 mg
    Participants received peposertib 250 mg once daily 5 days per week up to 5.5 weeks.
  • Drug: Capecitabine
    Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.
  • Radiation: Radiotherapy (RT)
    Participants received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.

More Details

Status
Completed
Sponsor
EMD Serono Research & Development Institute, Inc.

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.