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Cobimetinib and Atezolizumab in Advanced Rare Tumors

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ClinicalTrials.gov Identifier: NCT03108131
Recruitment Status : Recruiting
First Posted : April 11, 2017
Last Update Posted : February 19, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this research study is to learn if cobimetinib and atezolizumab can help to control advanced rare tumors. The safety of the drugs will also be studied.

This is an investigational study. Atezolizumab is FDA approved and commercially available for the treatment of metastatic (has spread) non-small cell lung cancer (NSCLC). Cobimetinib is FDA approved in combination with another drug called vemurafenib for the treatment of metastatic melanoma.

It is investigational to use atezolizumab and cobimetinib to treat advanced rare tumors.

The study doctor can explain how the study drugs are designed to work.

Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Digestive Organs Melanoma and Other Malignant Neoplasms of Skin Appendiceal Adenocarcinoma Cutaneous Squamous Cell Carcinoma Small Bowel Adenocarcinoma Drug: Cobimetinib Drug: Atezolizumab Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-label, Single-arm, Multi-cohort, Proof-of-principle Study to Investigate the Efficacy of Cobimetinib and Atezolizumab in Advanced Rare Tumors
Actual Study Start Date : April 7, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020


Arm Intervention/treatment
Experimental: Appendiceal Adenocarcinoma
Participants receive Cobimetinib 60 mg by mouth on Days 1−21 plus Atezolizumab 840 mg by vein on Day 1 and Day 15 in a 28-day cycle.
Drug: Cobimetinib
60 mg by mouth on Days 1−21 in a 28-day cycle.

Drug: Atezolizumab
840 mg by vein on Day 1 and Day 15 in a 28-day cycle.
Other Name: MPDL3280A

Experimental: Cutaneous Squamous Cell Carcinoma
Participants receive Cobimetinib 60 mg by mouth on Days 1−21 plus Atezolizumab 840 mg by vein on Day 1 and Day 15 in a 28-day cycle.
Drug: Cobimetinib
60 mg by mouth on Days 1−21 in a 28-day cycle.

Drug: Atezolizumab
840 mg by vein on Day 1 and Day 15 in a 28-day cycle.
Other Name: MPDL3280A

Experimental: Small Bowel Adenocarcinoma
Participants receive Cobimetinib 60 mg by mouth on Days 1−21 plus Atezolizumab 840 mg by vein on Day 1 and Day 15 in a 28-day cycle.
Drug: Cobimetinib
60 mg by mouth on Days 1−21 in a 28-day cycle.

Drug: Atezolizumab
840 mg by vein on Day 1 and Day 15 in a 28-day cycle.
Other Name: MPDL3280A




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 8 weeks ]
    ORR (partial response (PR) or complete response (CR) measured as per RECIST 1.1.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: 2 weeks after last dose of study drugs ]
    PFS assessed per RECIST v1.1.

  2. Progression-Free Survival (PFS) [ Time Frame: 2 weeks after last dose of study drugs ]
    PFS assessed per irRECIST.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Must be refractory or intolerant to standard lines of therapy.
  3. Presence of radiographically evaluable disease.
  4. 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 CTCAE v4.0 Grade 1 (with the exception of CTCAE v4.0 Grade 2 neuropathy) prior to start of treatment.
  5. ECOG Performance Status of 0-2.
  6. Age >/= 18 years.
  7. 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.
  8. Must have adequate hematologic function as evidenced by all of the following within 14 days prior to enrollment: ANC >/= 1,000/mcL; platelets >/= 75,000/mcL; and hemoglobin >/= 9 g/dL.
  9. Must have adequate hepatic function as evidenced by all of the following within 14 days prior to enrollment: AST, ALT, and ALP </= 3 x institutional upper limit of normal (IULN) without liver mets or </= 5 x IULN with liver metastases; and bilirubin </= 1.5 mg/dL.
  10. Must have adequate kidney function as evidenced by calculated creatinine clearance > 30 ml/min within 14 days prior to enrollment.
  11. Patients must be informed of 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
  12. 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.)

Exclusion Criteria:

  1. For individual baskets: Appendiceal Adenocarcinoma: Must not have clinically symptomatic malignant bowel obstruction; Cutaneous squamous cell carcinoma: None; Small bowel adenocarcinoma: Must not have clinically symptomatic malignant small bowel obstruction.
  2. 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).
  3. 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.
  4. 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.
  5. 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
  6. Active malignancy (other than 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.
  7. 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.
  8. Exclusion criteria related to study medication (any cancer immunotherapy including CD137 agonists, anti-PD-1, anti-PD-L1, or anti-CTLA4 or any MEK or ERK inhibitor).
  9. Left ventricular ejection fraction (LVEF) < institutional lower limit of normal or < 50%.
  10. History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis a. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. b. Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible. c. Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  11. Inclusion #10 cont'd) i. Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations ii. Rash must cover less than 10% of body surface area (BSA) iii. Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) iv. No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  12. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  13. History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection. a. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. b. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  14. Active tuberculosis or severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  15. Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN] or interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1.
  16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  17. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03108131


Contacts
Contact: Kanwal P. Raghav, MBBS 713-792-2828 KPRaghav@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech, Inc.
Investigators
Principal Investigator: Kanwal P. Raghav, MBBS M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03108131     History of Changes
Other Study ID Numbers: 2016-0869
NCI-2018-01399 ( Registry Identifier: NCI CTRP )
First Posted: April 11, 2017    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant Neoplasms of Digestive Organs
Melanoma and Other Malignant Neoplasms of Skin
Appendiceal Adenocarcinoma
Cutaneous Squamous Cell Carcinoma
Small Bowel Adenocarcinoma
Advanced rare tumors
Cobimetinib
Atezolizumab
MPDL3280A

Additional relevant MeSH terms:
Neoplasms
Melanoma
Carcinoma, Squamous Cell
Adenocarcinoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Neoplasms by Site
Skin Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs