- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02419495
Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies
Study Overview
Status
Conditions
- Metastatic Renal Cell Carcinoma
- Metastatic Lung Non-Small Cell Carcinoma
- Stage IVA Lung Cancer AJCC v8
- Stage IVB Lung Cancer AJCC v8
- Metastatic Melanoma
- Fallopian Tube Carcinoma
- Advanced Malignant Solid Neoplasm
- Stage III Lung Cancer AJCC v8
- Stage IV Lung Cancer AJCC v8
- Stage III Renal Cell Cancer AJCC v8
- Stage IV Renal Cell Cancer AJCC v8
- Stage IIIA Lung Cancer AJCC v8
- Stage IIIB Lung Cancer AJCC v8
- Metastatic Malignant Solid Neoplasm
- Unresectable Melanoma
- Ovarian Carcinoma
- Clinical Stage III Cutaneous Melanoma AJCC v8
- Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
- Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
- Pathologic Stage IIID Cutaneous Melanoma AJCC v8
- Pathologic Stage III Cutaneous Melanoma AJCC v8
- Pathologic Stage IIIA Cutaneous Melanoma AJCC v8
- Triple-Negative Breast Carcinoma
- Clinical Stage IV Cutaneous Melanoma AJCC v8
- Pathologic Stage IV Cutaneous Melanoma AJCC v8
- Stage IIIC Lung Cancer AJCC v8
- Primary Peritoneal Carcinoma
- Unresectable Lung Non-Small Cell Carcinoma
- Unresectable Renal Cell Carcinoma
Intervention / Treatment
- Drug: Carboplatin
- Biological: Nivolumab
- Biological: Ipilimumab
- Drug: Paclitaxel
- Biological: Pembrolizumab
- Drug: Cyclophosphamide
- Drug: Pemetrexed
- Drug: Doxorubicin
- Drug: Olaparib
- Drug: Fluorouracil
- Drug: Oxaliplatin
- Drug: Selinexor
- Drug: Capecitabine
- Drug: Leucovorin Calcium
- Drug: Irinotecan Hydrochloride
- Drug: Eribulin
- Drug: Topotecan
Detailed Description
PRIMARY OBJECTIVE:
I. To establish the safety and tolerability of selinexor when given in combination with standard chemotherapy or immunotherapy regimens.
SECONDARY OBJECTIVE:
I. To determine disease control rate, objective tumor response rate, and progression free survival of selinexor administered with standard chemotherapy or immunotherapy treatments.
EXPLORATORY OBJECTIVES:
I. To determine the correlation of translational biomarkers. II. To compare serial assessment of mutation status in biopsies obtained at baseline and progression after clinical response to combination therapy.
III. To assess the efficacy of olanzapine as incorporated in the National Comprehensive Cancer Network (NCCN) guidelines for the management of chemotherapy-induced nausea and cachexia.
OUTLINE: This is a dose-escalation study of selinexor. Patients are assigned to 1 of 15 treatment arms.
ARM A: Patients receive selinexor orally (PO) on days 1, 8, and 15 and carboplatin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM B: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles, of combination treatment, patients can continue single agent selinexor until disease progression.
ARM C: Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
ARM D: Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM E: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending on cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM F: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM G: Patients receive selinexor PO on days 1, 8, and 15 and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM H: Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil continuous IV and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM I: Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM J: Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM K: Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (ARM CLOSED)
ARM L: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM M: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARMS N AND O: Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM P: Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients may continue to receive selinexor and chemotherapy after confirmed progressive disease in the absence of clinical deterioration and if the investigator considers that the patient continues to receive benefit from the treatment.
After completion of study treatment, patients are followed up every 12 weeks for 1 year.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Conroe, Texas, United States, 77384
- MD Anderson in The Woodlands
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
Houston, Texas, United States, 77079
- MD Anderson West Houston
-
League City, Texas, United States, 77573
- MD Anderson League City
-
Sugar Land, Texas, United States, 77478
- MD Anderson in Sugar Land
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment; patients in Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) that have Food and Drug Administration (FDA)-approved indications for nivolumab, ipilimumab, and pembrolizumab do not have to fail first line nivolumab, ipilimumab, or pembrolizumab, and these patients may be treatment naïve if they have disease where pembrolizumab or nivolumab are FDA approved for the first-line setting
- For all arms except Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) patients must have failed prior standard curative chemotherapy for their disease; subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
- Patients must have measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- The patient must be recovered from a prior major surgery; the major surgery must be performed at least 4 weeks prior to consent date
- Platelets >= 125 x 10^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab] and expansion cohorts for all arms, platelets >= 100 x 10^9/L)
- Hemoglobin >= 10 g/dL (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab] and expansion cohorts for all arms, hemoglobin >= 9 g/dL)
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab], ANC >= 1.0 x 10^9/L)
- Transfusions and growth factors are allowed
- Alanine transaminase (alanine aminotransferase [ALT]) =< 2 x upper normal limit (ULN) (in the expansion cohort, patients with known liver involvement may have ALT =< 5 x ULN); aspartate aminotransferase (AST) =< 2 x ULN (in the expansion cohort, patients with known liver involvement may have AST =< 5 x ULN)
- Alkaline phosphatase < 4 x ULN
- Total bilirubin =< 2 x ULN (in the expansion cohort, patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of =< 3 x ULN)
- Renal function defined as a calculated or measured glomerular filtration rate (GFR) >= 30 mL/min. For patients with renal cell carcinoma (RCC), the GFR may be defined as >= 25 mL/min
- The patient has recovered to grade =< 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia; the exceptions for such effects are allowed lab values of =< grade 2 specified elsewhere in these inclusion criteria
- Life expectancy of at least 12 weeks
- Able to swallow and retain oral medication
- Patients must give informed consent according to the rules and regulations of the individual participating sites
- Negative serum pregnancy test in women of childbearing potential within 7 days of first dose of treatment and patients of child-bearing potential must agree to use effective contraception during/after 3 months post dose; a woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant; this includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices
- For the Arm B (paclitaxel) expansion cohort, patients must have ovarian carcinoma, fallopian tube, or peritonea carcinoma
- For Arm C (eribulin) expansion cohort, patients must have triple negative breast cancer (eribulin naive)
- For Arm M (nivolumab) expansion phase, patients must have biopsiable disease
- For the Arm N (nivolumab and ipilimumab), patients must have metastatic or unresectable renal cell carcinoma (RCC)
- For the Arm O (nivolumab and ipilimumab) escalation and expansion Cohort O-1, patients must have metastatic or unresectable melanoma
- For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must have metastatic or advanced solid tumors (non-melanoma, non-renal cell carcinoma, or non- non-small cell lung carcinoma)
- For the Arm P (nivolumab and ipilimumab), patients must have metastatic or unresectable non-small cell lung carcinoma (NSCLC)
Exclusion Criteria:
- Evidence of complete or partial bowel obstruction
Patients with primary central nervous system (CNS) tumor or CNS tumor involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is:
- > 4 weeks from prior therapy completion (including radiation and/or surgery)
- Clinically stable with respect to the CNS tumor at the time of study entry
- Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement
- Not receiving anti-convulsive medications (that were started for brain metastases)
- Need of total parenteral nutrition
- Prior treatment with an agent targeting the exportin
- Allergic to selinexor or any of the chemotherapy intended to receive
- Pregnancy or lactation
- Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) =< 3 weeks prior to study drug administration date
- Chemotherapy, or immunotherapy or any other systemic anticancer therapy =< 3 weeks prior to study drug administration date; patients receiving anti-PD-1 treatment, and continue to receiving this treatment in combination with selinexor (Arms L, M, N, O, and P), can start receiving the selinexor and anti-PD-1 combination without washout of the prior anti-PD-1 antibody
- Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated)
- Major surgery within four weeks before consent date
- Unstable cardiovascular function: symptomatic ischemia (chest pain of cardiac origin), or uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or myocardial infarction (MI) within 3 months of consent date
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose; active infection with concurrent treatment is acceptable only if the patient is clinically stable
- Significantly diseased (as determined by the principal investigator [PI] or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea
- Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date
- Concurrent therapy with approved or investigational anticancer therapeutics
- Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception; highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 3 months after the end of study treatment; women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months)
- For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects with an active, known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
- For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or other form of immunosuppressive therapy within 7 days before the first dose of study treatment; use of inhaled or topical steroids or systemic corticosteroids =< 10 mg is permitted; in addition, physiologic steroid replacement with hydrocortisone is allowed
- For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), history of a prior grade 3 or 4 immune-related adverse event (irAE) or any grade ocular irAE from prior immunotherapy
- For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must not have melanoma, RCC, or NSCLC
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (selinexor, carboplatin) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1.
Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After 6 cycles, patients can continue single agent selinexor until disease progression.
|
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arm B (selinexor, paclitaxel)
Patients receive selinexor PO twice weekly (e.g.
Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14.
Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
After 8 cycles of combination treatment, patients can continue single agent selinexor until disease progression.
|
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arm C (selinexor, eribulin)
Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After 6 cycles, patients can continue single agent selinexor until disease progression.
|
Given PO
Other Names:
Given IV
Other Names:
|
Experimental: Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1.
Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After 6 cycles, patients can continue single agent selinexor until disease progression.
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1.
Treatment repeats every 21 days for up to 8 cycles depending con cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity.
After 6 to 8 cycles, patients can continue single agent selinexor until disease progression.
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1.
Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After 6 cycles, patients can continue single agent selinexor until disease progression.
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arm G (selinexor, topotecan hydrochloride) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, and 15 and topotecan hydrochloride IV over 30 minutes on days 1-5.
Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
After 8 cycles, patients can continue single agent selinexor until disease progression.
|
Given PO
Other Names:
Given IV
Other Names:
|
Experimental: Arm H (selinexor, FOLFIRI) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil IV continuously over 48 hours and leucovorin calcium IV over 2 hours on days 1 and 15.
Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After 6 cycles, patients can continue single agent selinexor until disease progression.
|
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Arm I (selinexor, irinotecan hydrochloride) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
After 8 cycles, patients can continue single agent selinexor until disease progression.
|
Given PO
Other Names:
Given IV
Other Names:
|
Experimental: Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1.
Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
After 8 cycles, patients can continue single agent selinexor until disease progression.
|
Given IV
Other Names:
Given PO
Other Names:
Given PO
Other Names:
|
Experimental: Arm K (selinexor, olaparib) (ARM CLOSED)
Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Given PO
Other Names:
Given PO
Other Names:
|
Experimental: Arm L (selinexor, pembrolizumab)
Patients receive selinexor PO twice weekly (e.g.
Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arm M (selinexor, nivolumab
Patients receive selinexor PO twice weekly (e.g.
Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arm P (selinexor, nivolumab, ipilimumab)
Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1.
Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Arms N and O (selinexor, nivolumab, ipilimumab)
Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1.
Cycles repeat every 3 weeks for 4 cycles.
Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1.
Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: Up to 3 years
|
Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
|
Up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease control rate (complete response, partial response + stable disease for at least 6 months
Time Frame: Up to 3 years
|
Assessed according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria).
Estimated separately for each cohort with appropriate 95% confidence intervals.
|
Up to 3 years
|
Objective tumor response rate (complete response + partial response)
Time Frame: Up to 3 years
|
Assessed according to RECIST 1.1 criteria.
Estimated separately for each cohort with appropriate 95% confidence intervals.
|
Up to 3 years
|
Progression-free survival (PFS)
Time Frame: The time between the course 1 start date and the date of disease progression or death, whichever is reported first, assessed up to 3 years
|
PFS distribution will be estimated using the Kaplan-Meier product limit method and summary measures such as the median value and probabilities will be reported at selected times (with appropriate 95% confidence intervals).
|
The time between the course 1 start date and the date of disease progression or death, whichever is reported first, assessed up to 3 years
|
Overall survival (OS)
Time Frame: Up to 3 years
|
OS distribution will be estimated using the Kaplan-Meier product limit method and summary measures such as the median value and probabilities will be reported at selected times (with appropriate 95% confidence intervals).
|
Up to 3 years
|
Incidence of adverse events
Time Frame: Up to 3 years
|
Will be graded according to NCI CTCAE version 4.03.
|
Up to 3 years
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Serial mutations in biopsies
Time Frame: Up to 30 days after last dose of treatment
|
Up to 30 days after last dose of treatment
|
Severity of nausea and vomiting
Time Frame: Up to 3 years
|
Up to 3 years
|
Change in weight
Time Frame: Baseline up to 3 years
|
Baseline up to 3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Aung Naing, MD, M.D. Anderson Cancer Center
Publications and helpful links
General Publications
- Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Fu S, Subbiah V, Hong DS, Yap TA, Shah J, Milton DR, McQuinn L, Gong J, Tran Y, Carter BW, Colen R, Meric-Bernstam F, Naing A. Selinexor in combination with standard chemotherapy in patients with advanced or metastatic solid tumors. Exp Hematol Oncol. 2021 Dec 29;10(1):59. doi: 10.1186/s40164-021-00251-0.
- Thein KZ, Karp DD, Tsimberidou A, Gong J, Sulovic S, Shah J, Milton DR, Hong DS, Janku F, McQuinn L, Stephen BA, Colen R, Carter BW, Yap TA, Piha-Paul SA, Fu S, Meric-Bernstam F, Naing A. Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study. Invest New Drugs. 2022 Apr;40(2):290-299. doi: 10.1007/s10637-021-01188-1. Epub 2021 Sep 25. Erratum In: Invest New Drugs. 2021 Nov 3;:
- Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Zarifa A, Shah J, Milton DR, Bean S, McQuinn L, Gong J, Colen R, Carter BW, Subbiah V, Ogbonna DC, Pant S, Meric-Bernstam F, Naing A. Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study. Invest New Drugs. 2021 Oct;39(5):1357-1365. doi: 10.1007/s10637-021-01119-0. Epub 2021 Apr 28. Erratum In: Invest New Drugs. 2022 Apr;40(2):461.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Lung Diseases
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Breast Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Kidney Neoplasms
- Neuroendocrine Tumors
- Nevi and Melanomas
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Neoplasms
- Carcinoma, Renal Cell
- Breast Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Carcinoma
- Melanoma
- Skin Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Micronutrients
- Poly(ADP-ribose) Polymerase Inhibitors
- Antibiotics, Antineoplastic
- Vitamins
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Immune Checkpoint Inhibitors
- Topoisomerase I Inhibitors
- Antidotes
- Vitamin B Complex
- Hematinics
- Folic Acid Antagonists
- Cyclophosphamide
- Carboplatin
- Paclitaxel
- Fluorouracil
- Olaparib
- Capecitabine
- Oxaliplatin
- Nivolumab
- Pembrolizumab
- Leucovorin
- Irinotecan
- Calcium
- Levoleucovorin
- Albumin-Bound Paclitaxel
- Doxorubicin
- Liposomal doxorubicin
- Daunorubicin
- Topotecan
- Folic Acid
- Calcium, Dietary
- Pemetrexed
- Ipilimumab
- Camptothecin
Other Study ID Numbers
- 2014-0640 (Other Identifier: M D Anderson Cancer Center)
- NCI-2015-00693 (Registry Identifier: NCI-Clinical Trial Registry)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Renal Cell Carcinoma
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City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Renal Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Advanced Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v8 | Stage IV Renal Cell Cancer AJCC v8 | Metastatic Sarcomatoid Renal Cell Carcinoma | Advanced Renal Cell Carcinoma | Unresectable Renal Cell... and other conditionsUnited States
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NewLink Genetics CorporationCompletedMetastatic Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Metastatic Kidney Cancer | Refractory Renal Cell Carcinoma | Metastatic Clear-cell Renal CancerUnited States
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iOMEDICO AGNovartis PharmaceuticalsCompletedCarcinoma, Renal Cell | Clear-cell Metastatic Renal Cell Carcinoma | Locally Advanced and/or Metastatic Renal Cell CarcinomaGermany
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Jonsson Comprehensive Cancer CenterBeiGene; Driven To CureWithdrawnMetastatic Renal Cell Carcinoma | Stage IV Renal Cell Cancer AJCC v8 | Papillary Renal Cell Carcinoma | Collecting Duct Carcinoma | Unresectable Renal Cell Carcinoma | Hereditary Leiomyomatosis and Renal Cell Carcinoma | Clear Cell Papillary Renal Neoplasm | Hereditary Papillary Renal Cell Carcinoma and other conditionsUnited States
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Centre Hospitalier Universitaire de Saint EtienneTerminatedMetastatic Renal Cell Carcinoma | Metastatic Kidney CancerFrance
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Roswell Park Cancer InstituteIovance Biotherapeutics, Inc.WithdrawnMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Unresectable Renal Pelvis Urothelial Carcinoma | Unresectable Ureter Urothelial CarcinomaUnited States
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National Cancer Institute (NCI)RecruitingStage IV Renal Cell Cancer AJCC v8 | Sarcomatoid Renal Cell Carcinoma | Stage IV Bladder Cancer AJCC v8 | Stage IV Urethral Cancer AJCC v8 | Stage IVB Prostate Cancer AJCC v8 | Bladder Adenocarcinoma | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Collecting Duct Carcinoma | Bladder... and other conditionsUnited States, Puerto Rico
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Duke UniversityCompletedMetastatic Renal Cell Carcinoma | Metastatic Urothelial Carcinoma | Metastatic Castration-resistant Prostate Cancer (mCRPC)United States
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Prometheus LaboratoriesCompletedMetastatic Renal Cell Carcinoma | Metastatic MelanomaUnited States
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Association Pour La Recherche des Thérapeutiques...CompletedClear-cell Metastatic Renal Cell Carcinoma | Clear-cell Renal CarcinomaFrance
Clinical Trials on Carboplatin
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Eisai Inc.CompletedCancerUnited States, Austria, India
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Samyang Biopharmaceuticals CorporationCompleted
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NHS Greater Glasgow and ClydeCompletedOvarian Cancer | Fallopian Tube Cancer | Primary Peritoneal Cavity CancerUnited Kingdom, Australia, New Zealand
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Duke UniversityCompletedBrain and Central Nervous System TumorsUnited States, Canada
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National Cancer Institute (NCI)CompletedBreast Cancer | Ovarian CancerUnited States
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H. Lee Moffitt Cancer Center and Research InstituteNational Cancer Institute (NCI)CompletedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
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Eli Lilly and CompanyCompletedLung NeoplasmsUnited States
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National Cancer Institute (NCI)Children's Oncology GroupCompletedBrain and Central Nervous System TumorsUnited States, Canada, Puerto Rico, Australia, Netherlands, New Zealand, Switzerland
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All India Institute of Medical Sciences, New DelhiCouncil of Scientific and Industrial Research, IndiaUnknownIntraocular RetinoblastomaIndia
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MEI Pharma, Inc.CompletedPeritoneal Neoplasms | Ovarian Cancer | Fallopian Tube CancerUnited States, Spain, Belgium, United Kingdom, Australia, Italy, Poland