Clinical trial NCT03770689: Study of Peposertib in Combination With Capecitabine and RT in Rectal Cancer
Official title: A Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor Peposertib (M3814) in Combination With Capecitabine and RT in Participants With Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Rectal Cancer
Keywords: DNA-PK inhibitor
Peposertib
capecitabine
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2018-12-10
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC)
timeFrame: Time from first study intervention up to 19 weeks (including 5.5 weeks of treatment and 13.5 weeks of short term safety follow-up period)
Secondary outcomes:
measure: Number of Participants Wtih Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5.0
timeFrame: Time from first study intervention up to long term safety follow-up period (Up to Month 35)
measure: Number of Participants With Abnormalities [Grade Greater Than or Equals to (>=) 3] in Laboratory Test Values
timeFrame: Time from first study intervention up to long term safety follow-up period (Up to Month 35)
measure: Number of Participants With Markedly Abnormal Vital Sign Measurements
timeFrame: Time from first study intervention up to long term safety follow-up period (Up to Month 35)
measure: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
timeFrame: Time from first study intervention up to long term safety follow-up period (Up to Month 35)
measure: Percentage of Participants With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)
timeFrame: At Week 15
measure: Disease-free Survival
timeFrame: Time from first study intervention up to approximately 35 months
measure: Percentage of Participants With Pathological Complete Response (pCR)
timeFrame: At Week 15
measure: Percentage of Participants With Clinical Complete Response (cCR)
timeFrame: At Week 15
measure: Time From Surgery to Local Recurrence
timeFrame: Time from surgery up to 15 months
measure: Time From Surgery to Distant Metastasis
timeFrame: Time from surgery up to 15 months
measure: Neoadjuvant Rectal (NAR) Score
timeFrame: At Week 15
measure: Maximum Observed Plasma Concentration (Cmax) of Peposertib
timeFrame: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Fraction Day 1 and Fraction Day 9
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib
timeFrame: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Peposertib
timeFrame: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
measure: Total Body Clearance Following Oral Administration (CL/f) of Peposertib
timeFrame: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1
measure: Apparent Volume of Distribution (Vz/f) of Peposertib
timeFrame: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
measure: Apparent Terminal Half-life (t1/2) of Peposertib
timeFrame: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University - Pediatric Respiratory Medicine
state: Connecticut
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Great Neck
country: United States
facility: Northwell Health, Inc
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center (MSKCC) - New York
state: New York
city: Columbus
country: United States
facility: Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center - Hematology/Oncology
state: Ohio
city: Charleston
country: United States
facility: Med. Univ. of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System University Medical Center (ITOR)
state: South Carolina
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Dept of Oncology
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Oncologia
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: