Appendix Adenocarcinoma, Locally Advanced Malignant Neoplasm, Locally Advanced Skin Squamous Cell Carcinoma, Metastatic Malignant Neoplasm, Metastatic Skin Squamous Cell Carcinoma, Metastatic Small Intestinal Adenocarcinoma, Rare Lesion, Rare Neoplastic Syndrome, Refractory Malignant Neoplasm, Skin Squamous Cell Carcinoma, Stage IV Small Intestinal Adenocarcinoma AJCC v8, Unresectable Malignant Neoplasm
Conditions
Brief summary
This phase II trial studies how well cobimetinib and atezolizumab work in treating participants with rare tumors that have spread to other places in the body (advanced) or that does not respond to treatment (refractory). Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cobimetinib and atezolizumab may work better in treating participants with advanced or refractory rare tumors.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the efficacy of cobimetinib plus atezolizumab (COTEZO) in cohorts of advanced rare tumors using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. SECONDARY OBJECTIVES: I. To determine progression-free survival (PFS) on COTEZO in cohorts of advanced rare tumors per RECIST v1.1 and immune-related (ir)RECIST. II. To determine overall survival (OS) on COTEZO in cohorts of advanced rare tumors. III. To determine disease control rate (DCR) and duration of response (DOR) on COTEZO in cohorts of advanced rare tumors per RECIST v1.1 and irRECIST. IV. To determine objective response rate (ORR) per immune-related RECIST criteria. V. To determine safety profile and adverse events encountered by patients with advanced rare tumors treated with COTEZO. VI. To collect and bank tumor tissue and peripheral blood for future correlative analyses from patients with advanced rare tumors treated with COTEZO. OUTLINE: Participants receive cobimetinib orally (PO) once daily (QD) on days 1-21 and atezolizumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants followed up every 3 months thereafter.
Interventions
DRUGAtezolizumab
Given IV
DRUGCobimetinib
Given PO
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be informed of the investigational nature of this study and must be willing to give written informed consent in accordance with institutional and federal guidelines. Patients must be able to comply with the requirements and assessments of the study protocol * Must have histologically or cytologically documented rare tumor as defined per protocol that is metastatic or locally advanced and unresectable. Patients with locally advanced cutaneous squamous cell carcinoma that are technically resectable but in whom surgery is expected to lead to substantial function impairment or disfigurement are eligible * Must be refractory or intolerant to standard lines of therapy * Must have completed prior chemotherapy, immunotherapy, or radiation therapy at least 14 days prior to start of treatment and all toxicity must be resolved to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 1 (with the exception of CTCAE v4.0 grade 2 neuropathy) prior to start of treatment * Presence of radiographically evaluable disease * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 * Tissue Parameters: a. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 4 unstained slides, with an associated pathology report, for testing of tumor PD-L1 expression (tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable). b. Tumor tissue should be of good quality based on total and viable tumor content. Fine needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable. For core-needle biopsy specimens, at least three cores should be submitted for evaluation. c. Patients who do not have tissue specimens meeting eligibility requirements must be willing to undergo a biopsy during the screening period * Absolute neutrophil count (ANC) \>= 1,000/mcL (obtained within 14 days prior to enrollment) * Platelets \>= 75,000/mcL (obtained within 14 days prior to enrollment) * Hemoglobin \>= 9 g/dL (obtained within 14 days prior to enrollment) * Calculated creatinine clearance \> 30 ml/min (obtained within 14 days prior to enrollment) * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =\< 3 x institutional upper limit of normal (IULN) without liver mets or =\< 5 x IULN with liver metastases (obtained within 14 days prior to enrollment) * Bilirubin =\< 1.5 mg/dL (obtained within 14 days prior to enrollment) * Able to swallow pills * Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for \>= 1 year * Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (e.g., implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception) * For individual baskets: * Appendiceal adenocarcinoma * Not considered candidate for curative surgery * Cutaneous squamous cell carcinoma * Patients with either metastatic or locally advanced cutaneous squamous cell carcinoma that are technically resectable but in whom surgery is expected to lead to substantial function impairment or disfigurement are eligible * Small bowel adenocarcinoma * Must be refractory or intolerant to at least one line of fluorouracil (5FU)-based chemotherapy for metastatic disease
Exclusion criteria
* Presence of brain metastases (unless they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to enrollment provided patient is neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to enrollment) * Uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, severe infection, severe malnutrition, unstable angina, class III-IV New York Heart Association (NYHA) congestive heart failure, ventricular arrhythmias, active ischemic heart disease, or myocardial infarction within 6 months prior to enrollment * History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration * Patients will be excluded from study participation if they currently are known to have any of the following risk factors for RVO: a. Glaucoma with intraocular pressure \>= 21 mmHg b. Grade \>= 2 serum cholesterol c. Grade \>= 2 hypertriglyceridemia d. Grade \>= 2 or symptomatic hyperglycemia (fasting) e. Grade \>= 2 uncontrolled hypertension (patients with a history of hypertension controlled with anti-hypertensive medication to grade =\< 1 are eligible) * Active malignancy (other than colorectal carcinoma \[CRC\]) or a history of prior malignancy within the past 3 years. Adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ, other low grade lesions such as incidental appendix carcinoid, or any other cancer from which the patient has been disease and treatment free for two years are allowed. Prostate cancer patients on active surveillance are eligible * Pregnant or nursing patients due to risk of fetal or nursing infant harm. Women/men of reproductive potential who do not agree to use an effective contraceptive method while on study and for at least 6 months after study treatment *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Patient will be on study up to 3 years | To evaluate the efficacy of cobimetinib plus atezolizumab (COTEZO) in cohorts of advanced rare tumors using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Efficacy as determined by complete response and partial response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | 3 years | Disease Control Rate (DCR) includes patients with tumor maintained at Stable Disease (SD), Partial Response (PR) and Complete Response (CR). |
| Progression-Free Survival (PFS) | 3 years | Progression free survival (PFS) is defined as the time from randomization until first evidence of disease progression or death |
| Overall Survival | 3 years | Overall survival (OS) is defined as the time from randomization to death |
Countries
United States
Participant flow
Recruitment details
Out of the 49 patients that was enrolled at MD Anderson Cancer Center Houston, Tx, only 20 patients had Small Bowel Adenocarcinoma. The rest had other solid tumors and their data was not used in the analysis for the group of patients with Small Bowel Adenocarcinoma.
Participants by arm
| Arm | Count |
|---|---|
| Small Bowel Adenocarcinoma Must be refractory or intolerant to at least one line of 5FU-based chemotherapy for metastatic disease and must not have clinically symptomatic malignant small bowel obstruction. Cobimetinib (60 mgorally once daily for days 1 - 21) and atezolizumab (840 mg intravenously every 2 weeks) every 28-day cycle. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Small Bowel Adenocarcinoma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 20 |
| other Total, other adverse events | 9 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Overall Response Rate (ORR)
To evaluate the efficacy of cobimetinib plus atezolizumab (COTEZO) in cohorts of advanced rare tumors using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Efficacy as determined by complete response and partial response.
Time frame: Patient will be on study up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Small Bowel Adenocarcinoma | Overall Response Rate (ORR) | 2 Participants |
Secondary
Disease Control Rate (DCR)
Disease Control Rate (DCR) includes patients with tumor maintained at Stable Disease (SD), Partial Response (PR) and Complete Response (CR).
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Bowel Adenocarcinoma | Disease Control Rate (DCR) | 45 percentage of participants |
Secondary
Overall Survival
Overall survival (OS) is defined as the time from randomization to death
Time frame: 3 years
Population: 2 of the patients was not included in the analysis of PFS because their surgical cancellations were unrelated to progressive disease.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Small Bowel Adenocarcinoma | Overall Survival | 8.8 months |
Secondary
Progression-Free Survival (PFS)
Progression free survival (PFS) is defined as the time from randomization until first evidence of disease progression or death
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Small Bowel Adenocarcinoma | Progression-Free Survival (PFS) | 2.4 months |