MEDI4736 With Selumetinib for KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)

NCT03004105 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 2016-0060
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical research study is to learn if MEDI4736 given in combination with selumetinib can help to control advanced lung cancer. The safety of this drug combination will also be studied.

Conditions

Malignant Neoplasm of Respiratory and Intrathoracic Organ Carcinoma; Advanced Lung Cancer; Recurrent Nonsmall Cell Lung Cancer

Keywords

Malignant Neoplasm of Respiratory and Intrathoracic Organ Carcinoma; Advanced Lung Cancer; Recurrent Nonsmall Cell Lung Cancer; Selumetinib; AZD6244; Durvalumab; MEDI4736

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression-free survival (PFS) defined as the duration of time from start of treatment for patients in the safety run-in and from randomization for patients who are randomized to time of progression or death, whichever occurs first.

  42 months

Secondary Outcomes (1)

• Response Rate

  Every 8 weeks for 1 year

Study Arms (3)

Intermittent Arm - Selumetinib + Durvalumab

EXPERIMENTAL

Intermittent Arm - Participants receive Selumetinib at 75 mg by mouth twice a day for 7 days on and 7 days off, and Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle.

Drug: Selumetinib; Drug: Durvalumab; Behavioral: Phone Calls

Safety Run In

EXPERIMENTAL

Short safety run-in prior to the start of randomization. Participants on the safety run-in treated with Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle. Safety run-in beginning dose is Selumetinib 50 mg by mouth twice a day on Days 1 through 28 of a 28 day cycle. During the safety run in portion of the trial, enrollment will be open to all comers, regardless of KRAS mutation status.

Drug: Selumetinib; Drug: Durvalumab

Continuous Arm - Selumetinib + Durvalumab

EXPERIMENTAL

Continuous Arm - Participants take Selumetinib twice daily on Days 1 to 28 of a 28 day cycle. Dose determined by safety run-in. Participants receive Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle.

Drug: Selumetinib; Drug: Durvalumab; Behavioral: Phone Calls

Interventions

Selumetinib DRUG

Safety Run-In - Beginning dose is Selumetinib 50 mg by mouth twice a day on Days 1 through 28 of a 28 day cycle Intermittent Arm - Participants receive Selumetinib at 75 mg by mouth twice a day for 7 days on and 7 days off. Continuous Arm - Participants take Selumetinib twice daily on Days 1 to 28 of a 28 day cycle. Dose determined by safety run-in.

Also known as: AZD6244

Continuous Arm - Selumetinib + Durvalumab; Intermittent Arm - Selumetinib + Durvalumab; Safety Run In

Durvalumab DRUG

Safety Run-In, Intermittent Arm, Continuous Arm - Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle.

Also known as: MEDI4736

Continuous Arm - Selumetinib + Durvalumab; Intermittent Arm - Selumetinib + Durvalumab; Safety Run In

Phone Calls BEHAVIORAL

About every 6 months, participant called by a member of the study staff to ask how participant is doing and if participant has started any new treatments outside of the study. These calls should last about 10 minutes each time.

Continuous Arm - Selumetinib + Durvalumab; Intermittent Arm - Selumetinib + Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed recurrent non-small cell lung cancer not amendable to curative intent therapy or stage IV NSCLC.
• Known KRAS mutation status by CLIA certified test. Patients in the safety run-in are not required to have a tumor with mutant KRAS. In the randomized portion of the trial, only patients with KRAS mutation are eligible.
• Documented progression following at least one line of chemotherapy for metastatic or recurrent disease, or progression within 6 months of receiving adjuvant chemotherapy or concurrent chemotherapy for early stage or locally advanced disease.
• Biopsy accessible disease and willingness to undergo tumor biopsy.
• Measurable disease by RECIST 1.1.
• Age\>/= 18 years.
• ECOG performance status 0 or 1.
• Ability to take pills by mouth.
• Patients must have normal organ and marrow function as defined: leukocytes \>/=3,000/mcL, absolute neutrophil count \>/=1,500/mcL, platelets \>/=100,000/mcL, hemoglobin \>/9.0g/dL, total bilirubin \</=1.5 x upper limit of normal (ULN) (higher is allowed if in the setting of known Gilbert's disease), AST(SGOT)/ALT(SGPT) \</=2.5 x institutional upper limit of normal or \</=5 x ULN if liver metastases are present, Alkaline phosphatase \</=3.5 x institutional upper limit of normal or \<6 x ULN if liver metastases are present, creatinine clearance \>/=50 mL/min/1.73\^2 by Cockcroft-Gault equation (creatinine clearance= (\[140-age\]x body mass)/(plasma creatinine x 72) x gender correction factor) or by 24-hour urine collection.
• Brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids.
• Females of childbearing potential must have a negative serum pregnancy test and must agree to use adequate contraception for the duration of the study and six months after. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Continued in #12
• Continued from #11: a) Acceptable effective methods of contraception for women include implants, injectables, combined oral contraceptives, some intrauterine devices/systems and sterilization including vasectomy of the partner, all being used in combination with barrier methods of contraception (e.g. condoms). b) True sexual abstinence is also an acceptable method of contraception. Continued in #13
• Continued from #12: Women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following age-specific requirements must also apply: i.)Women \< 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) must also be in the post-menopausal range (as per the institution). ii.)Women \>/= 50 years old: they would be consider post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses \> 1 year ago, or have had chemotherapy-induced menopause with \>1 year interval since last menses, or have had surgical sterilisation by either bilateral oophorectomy or hysterectomy.
• Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and 90 days after the last dose of study medication. a) Acceptable methods of contraception for men include the use of condoms with spermicidal foams/gels or prior vasectomy. b) True sexual abstinence is also an acceptable method of contraception.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Have received or are receiving an investigational medicinal product (IMP) or other systemic anticancer treatment within 4 weeks prior to the first dose of study treatment, or within a period during which the IMP or systemic anticancer treatment has not been cleared from the body (e.g. a period of 5 'half-lives'), whichever is the most appropriate and as judged by the investigator.
• Current or prior use of immunosuppressive medication within 14 days of the 1st dose of durvalumab, with the exception of intranasal and inhaled corticosteroids or oral corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment.
• Receipt of radiation therapy within 4 weeks prior to starting study treatment. Limited field of radiation for palliation at any time prior to the start of study treatment is acceptable if: i.) The lung is not in the radiation field ii.) The irradiated lesions are not used as target lesions.
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
• Prior treatment with a MEK, Ras, or Raf inhibitor, or CTLA4 inhibitor.
• Patients who are receiving any other investigational agents.
• Have any unresolved chronic toxicity with CTCAE grade \>/= 2, from previous anticancer therapy, except for alopecia.
• Known hypersensitivity to selumetinib or durvalumab or any excipient or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib or durvalumab.
• Active or prior documented autoimmune disease within the past 3 years. Patients with a history of vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis).
• Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and / or radiation, and has been stable without requiring corticosteroids nor anti-convulsant medications for at least 4 weeks prior to the first dose of study medication.
• Known history of previous clinical diagnosis of tuberculosis.
• History of primary immunodeficiency.
• History of organ transplant requiring therapeutic immunosuppression.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• AstraZeneca: collaborator
• MedImmune LLC: collaborator

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

AZD 6244; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Don L. Gibbons, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 28, 2016
• Study Start: May 1, 2018
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2024
• Last Updated: March 16, 2018

Record last verified: 2018-03