Clinical trial NCT03555149: A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)
Official title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-06-13
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (mCRC) that became refractory to first- and second-line standard therapies. Eligible patients will be assigned to one of several treatment arms.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy ≥ 3 months, as determined by the investigator
* Histologically confirmed adenocarcinoma originating from the colon or rectum
* Metastatic disease not amenable to local treatment
* Disease progression during or following not more than two separate lines of treatment for metastatic colorectal cancer (mCRC) that consisted of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy in combination with a biologic agent
* Measurable disease (at least one target lesion) according to RECIST v1.1
* Adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment

Exclusion Criteria:

* High microsatellite instability (MSI-H) tumor
* Presence of BRAFV600E mutation
* Prior treatment with any of the protocol-specified study treatments
* Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Biologic treatment within 2 weeks prior to initiation of study treatment, or other systemic treatment for CRC within 2 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Eligibility only for the control arm
* Prior allogeneic stem cell or solid organ transplantation
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
* Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
* Current treatment with anti-viral therapy for HBV
* Uncontrolled pleural effusion, pericardial effusion, ascites requiring recurrent drainage procedures (once monthly or more frequently), or tumor related-pain,
* Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12 mg/dL, or corrected serum calcium \>ULN)
* Symptomatic, untreated, or actively progressing CNS metastases
* History of leptomeningeal disease
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Active tuberculosis
* Severe infection within 4 weeks prior to initiation of study treatment
* Significant cardiovascular disease
* Grade ≥3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment
* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
* History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
* Inability to swallow medications
* Malabsorption condition that would alter the absorption of orally administered medications
* Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
* Urine dipstick ≥ 2+ protein or ≥ 3.5 g of protein in a 24-hour urine collection

Primary outcomes:
measure: Best Confirmed Overall Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: From randomization until disease progression or loss of clinical benefit (up to 4 years)
Secondary outcomes:
measure: Progression-Free Survival (PFS) as Determined by Investigator According to RECIST v1.1
timeFrame: From randomization up to the first occurrence of disease or death from any cause (up to 4 years)
measure: Overall Survival (OS)
timeFrame: From randomization up to death from any cause (up to 4 years)
measure: Percentage of Participants Who Were Alive at Landmark Timepoints for Overall Survival (OS)
timeFrame: 3, 6, 12, and 18 months
measure: Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
timeFrame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 4 years)
measure: Disease Control Rate (DCR), as Determined by the Investigator Per RECIST v1.1
timeFrame: From randomization until disease progression or loss of clinical benefit (up to 4 years)
measure: Percentage of Participants With at Least One Adverse Event (AE)
timeFrame: Adverse event data were collected from baseline up to 6 months after the last dose of study treatment (up to 640 days); deaths (all-cause) were reported from baseline through survival follow-up (up to 4 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: North Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Dijon Cedex
country: France
facility: Centre Georges François Leclerc; Pharmacie des Essais Cliniques
city: Lyon
country: France
facility: Centre Leon Berard
city: Toulouse
country: France
facility: Institut Claudius Regaud; Departement Oncologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center.
city: Lausanne
country: Switzerland
facility: CHUV; Departement d'Oncologie
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: