Purpose

The main purpose of the study is to define maximum tolerated dose (MTD), recommended Phase II dose (RP2D) of M3814 in combination with capecitabine and radiotherapy (RT) in Phase Ib and to evaluate the efficacy of M3814 in terms of Pathological Clinical Response (pCR)/Clinical Complete Response (cCR) when administered in combination with capecitabine and RT versus placebo, capecitabine, and RT in Phase II.

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 III).
  • Participants who received induction chemotherapy are allowed to be enrolled to this study except this induction is resulting in complete response.
  • 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 other than human immunodeficiency virus, hepatitis B virus, or hepatitis C virus, 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
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase Ib: M3814 + Capecitabine + RT
  • Drug: Phase Ib: M3814
    Participants will receive M3814 at an escalated dose starting from 50 mg once daily 5 days per week in first cohort up to week 6 and for the next cohorts M3814 dose will be determined by the Safety Monitoring Committee (SMC) guided by a Bayesian 2-parameter logistic regression model with overdose control.
  • Drug: Capecitabine
    Participants will receive capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week in Phase Ib and Phase II up to week 6.
  • Radiation: Radiotherapy (RT)
    Participants will receive RT of approximately 50 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions (corresponding to 5 to 5.5 weeks) Phase Ib and Phase II.
Experimental
Phase II: M3814 + capecitabine + RT
  • Drug: Capecitabine
    Participants will receive capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week in Phase Ib and Phase II up to week 6.
  • Radiation: Radiotherapy (RT)
    Participants will receive RT of approximately 50 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions (corresponding to 5 to 5.5 weeks) Phase Ib and Phase II.
  • Drug: Phase II: M3814
    Participants will receive M3814 50 mg or matching placebo at the RP2D once daily 5 days per week up to week 6.
Placebo Comparator
Phase II: Placebo + capecitabine + RT
  • Drug: Capecitabine
    Participants will receive capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week in Phase Ib and Phase II up to week 6.
  • Radiation: Radiotherapy (RT)
    Participants will receive RT of approximately 50 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions (corresponding to 5 to 5.5 weeks) Phase Ib and Phase II.
  • Drug: Phase II: Placebo
    Participants will receive Placebo matched to M3814 for 5 days per week up to week 6.

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10461

More Details

NCT ID
NCT03770689
Status
Recruiting
Sponsor
EMD Serono Research & Development Institute, Inc.

Study Contact

US Medical Information
888-275-7376
service@emdgroup.com

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.