Bioequivalence and the Tolerability and Antitumor Activity of Selinexor Combination Treatment

STATUS

Recruiting
participants needed

38
sponsor

Karyopharm Therapeutics Inc

Send

Updated on 19 February 2024

See if I qualify

cancer

serum pregnancy test

liver function tests

measurable disease

solid tumour

pembrolizumab

gilbert's syndrome

docetaxel

lung cancer

solid tumor

monoclonal antibodies

programmed cell death protein 1

selinexor

irinotecan

monoclonal antibody therapy

carcinoma

fluorouracil

leucovorin

drug test

combination therapy

stage iv non-small cell lung cancer

kras

systemic therapy

monoclonal protein

adjuvant therapy

cancer therapy

moderate hepatic impairment

metastatic solid tumor

metastatic nsclc

folfiri regimen

combined modality therapy

adjuvant

colorectal cancer

non-small cell lung cancer

small cell lung cancer

Summary

This is a Phase 1, two-part, two-arm, open-label study in patients with NSCLC who have had 1 or 2 prior lines of treatment, with 1 line containing a CPI, or patients with CRC who have had 2 prior lines of treatment (oxaliplatin- and irinotecan-based) and no prior immunotherapy. The study will comprise 2 treatment periods (Monotherapy and Combination Therapy). During the Monotherapy Period, the bioequivalence/relative bioavailability of different formulations of selinexor will be evaluated using a 2-sequence crossover design. During the Combination Therapy Period, the safety and preliminary anti-tumor activity of selinexor in combination with docetaxel (for patients with NSCLC) or pembrolizumab (for patients with CRC) will be evaluated.

Description

Monotherapy Period

For the Monotherapy Period of Study KCP-330-027, patients will be allocated to one of two test formulation treatment arms for once weekly dosing over a period of 3 weeks. A third test formulation of 100-mg oral suspension will be allocated on Week 3 to 6 patients in total out of the 38 patients planned to be enrolled. Approximately 38 patients will be enrolled, with a maximum of 20 patients for each disease type (NSCLC or CRC). In the CRC Cohort, at least 10 patients should have the KRAS mutation. Patients will be randomized to 1 of the 2 treatment arms; disease type (NSCLC or CRC) will be a randomization factor. The number of patients enrolled may be adjusted based on the results of the interim analysis performed after the first 16 pharmacokinetics (PK) evaluable patients have completed Week 2.

For Weeks 1 and 2 (and Week 3 for patients receiving the 100-mg oral suspension), following an overnight fast of at least 10 hours, patients will be fed a standard low-fat meal 30 minutes prior to administration of once weekly selinexor. Patients should finish the meal in 30 minutes or less; however, selinexor dose should be administered 30 minutes after start of the meal. Blood sampling for selinexor PK analyses will be collected predose (10 minutes before taking selinexor), 15 min (3 min), 30 min (3 min), 1 hour (5 min), 1.5 hours (7 min), 2 hours (10 min), 3 hours (10 min), 4 hours (10 min), 5 hours (10 min), 6 hours (10 min), 8 hours (20 min), 10 hours (20 min; optional timepoint), 24 hours (30 min), 30 hours (30 min), and 48 hours (1 hour) post selinexor dose. Practitioners must record the actual clock time for selinexor dose and each sample drawn.

If a patient experiences emesis during the first 6 hours of the PK sampling, the results will be excluded from the PK analysis dataset.

Safety will be evaluated through reporting of treatment-emergent adverse events (TEAEs), physical examinations (PE), and clinical laboratory testing.

Computed tomography (CT) or magnetic resonance imaging (MRI) will be performed at screening.

Patients who complete the Monotherapy Period will be considered for continuation to the Combination Therapy Period if they do not meet any exclusion criteria for reassessment. If a patient experiences significant toxicity related to selinexor and can't start the combination therapy immediately following monotherapy, dose interruption and weekly retesting are allowed for up to 21 days after the End of Monotherapy Treatment Visit. Patients requiring >21 days to recover from toxicities related to selinexor should be discussed with the Sponsor's Medical Monitor for documented approval to continue to the Combination Therapy Period. Reassessment may be extended then and following Medical Monitor approval up to 28 days.

Combination Therapy Period Patients enrolled in the Combination Therapy Period will receive combination treatment with selinexor once weekly and either docetaxel (NSCLC patients) or pembrolizumab (CRC patients) every 3 weeks until progressive disease (PD) or intolerable toxicity.

Safety will be assessed through the continuous reporting of AEs, regularly scheduled clinical laboratory tests (hematologic and chemical), and physical examinations.

Tumor assessment will be performed with either CT or MRI (CT with contrast preferred; for each patient, the imaging method should remain the same throughout the study).

Patients will be followed for up to 1 year after the 30-Day Safety Visit (approximately 30 days after the last dose of combination therapy). Patients who discontinued due to PD will be followed for survival, and patients who discontinued for reasons other than PD will have tumor assessments until PD or until the start of new anti-neoplastic therapy and will be followed for survival.

Details

Condition	Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer, Colorectal Cancer, Colorectal Cancer, Rectal disorder
Age	18years - 100years
Treatment	Pembrolizumab, Selinexor, Docetaxel
Clinical Study Identifier	NCT04256707
Sponsor	Karyopharm Therapeutics Inc
Last Modified on	19 February 2024

How understandable was the trial content above?

Hard to understand

Easy to understand

Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Patients are eligible to be included in the study only if they meet all of the
	following
	criteria
	Are 18 years of age
	Have histologically confirmed advanced or metastatic NSCLC or CRC (patients with either KRAS mutation or wild type are eligible; however, at least 10 patients with CRC must have KRAS-mutant disease)
	Patients must have evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
	Have received prior therapy as follows
	For patients with NSCLC, have received at least 1 but no more than 2 prior line(s) of systemic anti-cancer treatment with 1 regimen including a checkpoint inhibitor (CPI)
	For patients with CRC, have received 2 prior lines of systemic anti-cancer treatment (oxaliplatin- and irinotecan-based); no prior therapy with immunotherapy
	Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective (dual methods of) contraception throughout the study and for 1 week following the last dose of study drug; and male patients must use an effective barrier method of contraception throughout the study and for 1 week following the last dose of study drug if sexually active with a female of childbearing potential
	Willing to provide written informed consent in accordance with federal, local, and institutional guidelines and comply with all requirements of the trial
Exclusion Criteria
	Patients are excluded from the study if any of the following criteria apply
	Have an Eastern Cooperative Oncology Group (ECOG) performance status of 2
	Have a life expectancy of <12 weeks, as determined by the Investigator
	Have inadequate hepatic function defined as total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) > upper limit of normal (ULN). Patients with mild hepatic dysfunction (total bilirubin of 1 - 1.5 ULN or AST/ALT of 1 - 2 ULN) may be included in the study if approved by the Sponsor's Medical Monitor
	Have inadequate hematopoietic function defined as absolute neutrophil count (ANC) <1.5 10/L; platelet count (PLT) <100 10/L; or hemoglobin (Hb) <9 g/dL
	Had transfusions or hematopoietic growth factors <7 days of Day 1 dosing
	Have inadequate renal function defined as a calculated creatinine clearance (CrCl) of <20 mL/min using the formula of Cockcroft and Gault
	Have any other medical condition especially any gastrointestinal (GI) dysfunctions or GI disease that could interfere with the absorption of selinexor (e.g., inability to swallow tablets, malabsorption syndrome, a history of GI surgery which may result in intestinal blind loop, significant gastroparesis, unresolved nausea, vomiting, or diarrhea [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade >1]) or have any general inability to swallow and retain oral medications
	Unstable cardiovascular function
	symptomatic ischemia, or
	congestive heart failure of New York Heart Association Class 3, or
	myocardial infarction within 3 months of Day 1 dosing
	Received strong cytochrome P450 3A (CYP3A) inhibitors OR strong CYP3A inducers 7 days prior to Day 1 dosing
	Ongoing infection requiring parenteral antibiotics, antivirals, or antifungals on Day 1 dosing
	Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as
	Not recovered from major surgery 21 days prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous line for infusion are permitted
	Have ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade >1\. In specific cases, patients whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor
	Had last dose of previous anti-cancer therapy 14 days prior to Day 1 dosing
	Inability or unwillingness to undergo a series of PK sampling
	Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the NCCN Clinical Practice Guidelines in Oncology for antiemesis and anorexia/cachexia (palliative care)
	Serious psychiatric or medical conditions that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous
	In the opinion of the Investigator, patients who are significantly below their ideal body weight
	Known allergy to selinexor (all patients), docetaxel (NSCLC Cohort only), or pembrolizumab (CRC Cohort only)
	Female patients who are pregnant or lactating
	Patients with CRC who are to receive pembrolizumab
	had a diagnosis of immunodeficiency or are receiving systemic steroid therapy (>10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy
	are diagnosed with endocrinopathies, such as abnormal thyroid function. Patients on stable hormone replacement therapy are allowed
	have active autoimmune disease requiring systemic treatment during the past 2 years. Type 1 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
	The following exclusion criteria define patients to be excluded from the
	Combination Therapy Period upon completion of the Monotherapy Period
	\. Have PLT <100 10/L, ANC <1.0 10/L (for patients with NSCLC who are to
	receive docetaxel, ANC <1.5 10/L), or Hb <9 g/dL
	\. Have an ECOG performance status of 3
	\. Have not recovered or stabilized from nonhematologic toxicities related
	to selinexor, with recovery defined as Grade 1 or baseline for nonhematologic
	AEs. Patients with certain Grade 2 nonhematologic toxicities can be allowed
	following approval by the Sponsor's Medical Monitor
	Note: Dose interruption between the Monotherapy Period and the Combination
	Therapy Period is allowed for recovery from AEs. Patients requiring >21 days
	after the End of Monotherapy Treatment visit to recover from toxicities
	related to selinexor should be discussed with the Sponsor's Medical Monitor
	for approval to continue to the Combination Therapy Period
	\. For patients with CRC who are to receive pembrolizumab, have received
	live-attenuated vaccine against an infectious disease (e.g., influenza) 14
	days prior to Cycle 1 Day 1 (C1D1)
	\. For patients with NSCLC who are to receive docetaxel, have a bilirubin
	>ULN or AST and/or ALT >1.5 ULN concurrent with alkaline phosphatase >2.5 ULN

How to participate?

Step 1 Connect with a study center

Select a site
Send a message

You have contacted , on

Your message has been sent to the study team at ,

A copy of the message has been sent to your email

What happens next?

You can expect the study team to contact you via email or phone in the next few days.
Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Primary Contact

I am at least 18 years old.

By sending a message, I agree to share my information with the study team for the selected site and consent to receive emails and text messages for trial updates, notifications, and related communication. TrialX values your privacy; your information will be handled in accordance with our Privacy Policy

Step 2 Get screened

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

Step 3 Enroll in the clinical study

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Step 4 Get your study results

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

monoclonal antibodies

programmed cell death protein 1

selinexor

irinotecan

monoclonal antibody therapy

stage iv non-small cell lung cancer

moderate hepatic impairment

metastatic solid tumor

metastatic nsclc

folfiri regimen

combined modality therapy

adjuvant

colorectal cancer

non-small cell lung cancer

small cell lung cancer

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Study Definition

Wikipedia

Bioequivalence and the Tolerability and Antitumor Activity of Selinexor Combination Treatment