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Solid TumorPhase 1NCT03588039

Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors

A Phase 1 study testing Oraxol and Pembrolizumab in people with Solid Tumor, run by Athenex, Inc. at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open-label, Phase 1 dose-escalation study followed by a 2-arm expansion cohort of Oraxol administered in combination with pembrolizumab. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Solid Tumor
What is being tested?
Oraxol and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
4 sitesUnited States
Study dates
25 Oct 2018to 12 May 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eligible subjects must have/be:
  • Able to understand and sign an informed consent form
  • Age ≥18 years
  • Dose Escalation: Histologically confirmed metastatic or unresectable solid tumors for which pembrolizumab is an FDAapproved therapy
  • Dose Expansion: Histologically confirmed diagnosis of advanced or metastatic NSCLC or gastric/gastro-esophageal adenocarcinoma:
  • NSCLC:
Show all 32Show fewer
  • Subjects with actionable mutations or alterations must have progressed on prior FDA approved therapy for these aberrations.
  • Subjects must have progressed on a prior FDA-approved single agent immunotherapy (antiPD1/anti-PD-L1) in first line (1L) or progressed on a prior FDA approved immunotherapy + chemotherapy combination therapy in 1L, as long as the chemotherapy did not include a taxane.
  • Gastric/Gastro-esophageal
  • Histologically confirmed diagnosis of advanced or metastatic gastric/gastro-esophageal adenocarcinoma or esophageal squamous cell carcinoma.
  • Subjects must have progressed on previous anti-PD-1 therapy as single agent or combination therapy.
  • Must have at least one measurable site of disease as defined as per RECIST v1.1 criteria
  • ECOG Performance Status ≤1
  • The following laboratory values obtained ≤14 days prior to Cycle 1/Day 1 dosing:
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L
  • Platelet count ³100 x 109/L
  • Hemoglobin ≥9.0 g/dL
  • Total and direct bilirubin within normal range
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) £3 x upper limit of normal (ULN)
  • Gamma-glutamyl transferase (GGT) ≤5 x ULN
  • Alkaline phosphatase ≤3 x ULN or ≤5 x ULN if bone or liver metastasis is present
  • Serum creatinine £2 x ULN, or 24-hr urine creatinine clearance calculation ³ 50 mL/min
  • Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) ≤1.5 x ULN OR if a subject is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants for 7 days prior to receiving study treatment
  • Willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder
  • Subjects receiving warfarin who are otherwise eligible and who may be appropriately managed with low molecular weight heparin, in the opinion of the Investigator, may be enrolled in the study provided they are switched to low molecular weight heparin at least 7 days prior to receiving study treatment.
  • Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use a condom with spermicide and to not donate sperm during the study and for at least 30 days following last dose of Oraxol
  • Female subjects must be postmenopausal (>12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie, oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 30 days after their last dose of assigned study treatment. Abstinence is also an acceptable form of contraception.
  • Subjects who are of childbearing potential must have a negative serum pregnancy test at Screening and within 96 hours before Week 1 dosing.
  • Willing to return for follow-up
  • Willing to provide blood samples for correlative research purposes
  • Life expectancy of at least 3 months

Who cannot join

  • Eligible subjects must not have/be:
  • Subjects with history of prior treatment with taxanes (eg, paclitaxel, docetaxel, cabazitaxel) in expansion cohorts only
  • History of prior significant toxicity from anti-PD-1 or anti-PD-L1 therapy requiring discontinuation of treatment
  • Subjects who have received recent anti-cancer therapy defined by:
  • Chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy, and radiation) ≤28 days prior to starting study drug, or who have not recovered from side effects of such therapy
  • Last administration of nitrosurea or mitomycin-C ≤42 days prior to starting study drug, or who have not recovered from the side effects of such therapy
Show all 34Show fewer
  • Targeted therapy (eg, sunitinib, sorafenib, pazopanib) ≤14 days prior to starting study drug, or who have not recovered from the side effects of such therapy; or
  • Radiotherapy ≤28 days prior to starting study drug, or ≤14 days prior to starting study drug in the case of localized radiotherapy (eg, for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of pembrolizumab. The following are exceptions to this criterion: Intranasal, inhaled, topical corticosteroids, or local corticosteroid, injections (eg, intra-articular injection), systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or its equivalent.
  • Vaccinated with live, attenuated vaccines within 28 days of the first dose of the study drug
  • Active or prior documented autoimmune or inflammatory disorders (including but not limited to inflammatory bowel disease [eg, colitis, Crohn's disease], celiac disease, or other serious gastrointestinal (GI) chronic conditions associated with diarrhea; type 1 diabetes mellitus; multiple sclerosis; systemic lupus erythematosus; Wegener's granulomatosis; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis; uveitis; etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
  • Subjects with vitiligo or alopecia
  • Subjects with hypothyroidism (eg, following Hashimoto's thyroiditis) stable on hormone replacement therapy or psoriasis not requiring systemic treatment
  • Subject has impairment of GI function or GI disease that may significantly alter the absorption of study drugs (including gastric bypass surgery and total gastrectomy). Subjects with partial gastrectomy may be included in the trial.
  • Subjects who have undergone major surgery (eg, intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤28 days prior to starting study treatment, or subjects who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤7 days prior to starting study drug, or who have not recovered from side effects of such procedure or injury
  • Uncontrolled concurrent illness, including but not limited to ongoing or active serious infection requiring systemic antimicrobials (within 14 days prior to first dose of Oraxol), arterial hypertension (>160/100 mm/Hg on antihypertensive medications), uncontrolled endocrine diseases, altered mental status or psychiatric illness/social situations that would limit compliance with protocol requirements and/or obscure study results.
  • Known or suspected diagnosis of human immunodeficiency virus (HIV) or chronic active Hepatitis B or C, or cirrhosis.
  • Clinically significant pulmonary illness resulting in Grade ≥2 hypoxia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE, v4.03]) or any requirement for supplemental oxygen, or pulse oximetry less than 90% saturation on room air
  • Symptomatic or uncontrolled brain metastases requiring current treatment (less than 28 days from last cranial radiation or 28 days from last steroids use).
  • Impaired cardiac function or clinically significant cardiac disease including the following:
  • Clinically significant arrhythmias (except chronic well controlled atrial fibrillation)
  • New York Heart Association (NYHA) Class III or IV congestive heart failure
  • Angina pectoris ≤6 months
  • Myocardial infarction within the last 12 months
  • Subjects with a healing or open wound
  • Lack of recovery of prior AEs to Grade ≤1 severity (NCI CTCAE v4.03) (except alopecia) due to medications administered prior to the first dose of the trial drugs.
  • Any other condition or finding (including social situation) that in the opinion of the Investigator may render the patient at excessive risk for treatment complications or may not be able provide evaluable outcome information.
  • Pregnant or breast-feeding women
  • Known allergy to any of the formulation components of Oraxol (oral paclitaxel or HM30181A) or pembrolizumab
  • Currently taking following prohibited concomitant medication:
  • Medication known to be strong inhibitors (gemfibrozil) or inducers (rifampin) of cytochrome P450 (CYP)2C8. Subjects who are currently taking such medications but who are otherwise eligible may be enrolled if they discontinue the medication 14 days before dosing and remain off that medication during treatment with Oraxol.
  • Strong CYP3A4 inducer (eg, rifampin or St. John's Wort) or a strong CYP3A4 inhibitors (eg, ketoconazole) or a moderate CYP3A4 inhibitor including neurokinin 1 (NK1) inhibitors (eg, aprepitant and rolapitant) within 14 days prior to treatment administration
  • Medication known to be strong P-gp inhibitors or inducers. Subjects who are taking such medications but who are otherwise eligible may be enrolled if they discontinue the medication 7 days before dosing and remain off that medication during treatment with Oraxol.
  • An oral medication with a narrow therapeutic index known to be a P-gp substrate (eg, digoxin, dabigatran) within 1 day prior to start of Oraxol dosing in the study

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase 1 Study With Expansion Cohorts to Assess the Safety, Tolerability, and Activity of Oraxol (Paclitaxel + HM30181A) in Combination With Pembrolizumab in Subjects With Advanced Solid Malignancies

This is an open-label, Phase 1 dose-escalation study followed by a 2-arm expansion cohort of Oraxol administered in combination with pembrolizumab.

Read the detailed description

This is a two part study. The dose escalation part will enroll subjects with advanced solid tumors for which pembrolizumab is an FDA-approved therapy, to determine the MTD and identify the recommended phase 2 dose of paclitaxel administered as Oraxol in combination with pembrolizumab. Upon determination of the phase 2 dose, the dose expansion part will enroll subjects with advanced/metastatic gastric/gastro-esophageal, or NSCLC into 2 independent cohorts/arms to further evaluate the activity and safety of the study treatment.

Conditions
Solid Tumor
Being tested
Oraxol, Pembrolizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OraxolDrug

    Also called oral HM30181A + oral paclitaxel

    Oral paclitaxel will be supplied in capsules and oral HM30181AK-US will be supplied in tablets

  • PembrolizumabBiological

    Also called Keytruda

    Intravenously administered

Study groups in NCT03588039
Study groupRoleWhat they receive
Dose escalation-Arm 1ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 2 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab
Dose escalation-Arm 2ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 3 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab
Dose escalation-Arm 3ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 4 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab
Dose escalation-Arm 4ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab
Dose escalation-Arm 5ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab
Dose escalation-Arm 6ExperimentalDuring the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab
Dose expansion-Gastric/GEExperimentalThe dose expansion period will enroll subjects with gastric/gastro-esophageal cancer to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab
Dose expansion-NSCLC cancerExperimentalThe dose expansion period will enroll subjects with NSCLC to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.
Receives: Drug: Oraxol; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determination of MTD

    dose limiting toxicities occuring in the first cycle of therapy

    Measured: 3 weeks

  2. Tumor response rate

    Proportion of subjects in each arm and part 2 with confirmed tumor response

    Measured: 24 months

Secondary outcomes (7)

  1. Progression free survival (PFS)

    To determine the progression free survival after initiation of treatment with Oraxol in subjects

    Measured: 24 months

  2. Overall survival (OS)

    To determine the overall survival after initiation of treatment with Oraxol in subjects

    Measured: 24 months

  3. Duration of response (DOR)

    The duration of response will be measured in subjects associated with Oraxol administered in combination with pembrolizumab in subjects with advanced/metastatic gastric/gastro-esophageal, or NSCLC who have stable disease or progressed on previous anti-PD1 or anti-PDL1 therapy

    Measured: 24 months

  4. Pharmacokinetics of Oraxol

    Plasma concentrations of Oraxol

    Measured: Day 1 and day 2

  5. Disease Control Rate (DCR)

    The disease control rate, defined as the proportion of subjects whose best response is complete response (CR), partial response (PR), or stable disease (SD) divided by the total number of evaluable subjects in each cohort.

    Measured: 24 months

  6. Incidence of Adverse Events

    The incidence of Treatment Emergent Adverse Events and Treatment-related Adverse Events will be summarised using descriptive statistics.

    Measured: 24 months

  7. Time to response

    To determine the time to response, defined as the time from the treatment initiation to first documented response

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2018
  2. Study start25 Oct 2018
  3. Primary completion12 May 2023
  4. Study completion12 May 2023

Why it stopped: Study terminated due to lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03588039
Sponsor's protocol ID
KX-ORAX-011
Other IDs
KEYNOTE-E06
Status last verified
May 2023
First submitted
13 Jun 2018
Last updated
19 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oraxol and Pembrolizumab in people with Solid Tumor, run by Athenex, Inc. at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study terminated due to lack of funding). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of MTD (time frame: 3 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03588039.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2023.

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