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Neoplasm MalignantPhase 1NCT04726332

Study of XL102 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (QUARTZ-101)

A Phase 1 study testing XL102, Fulvestrant and Abiraterone in people with Neoplasm Malignant and Epithelial Ovarian Cancer, run by Exelixis at 5 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 a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, PK, antitumor activity, and effect on biomarkers of XL102 administered orally alone and in multiple combination regimens to subjects with advanced solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
XL102, Fulvestrant and Abiraterone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
5 sitesUnited States
Study dates
10 Feb 2021to 2 May 2024
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent.
  • Dose-Escalation Stage Cohort A (Solid Tumors): The subject has a solid tumor that is unresectable or metastatic and for which life-prolonging measures do not exist or available therapies are intolerable or no longer effective.
  • Dose-Escalation Stage Cohort B and Cohort-Expansion Stage Cohorts F and H (Hormone Receptor-Positive Breast Cancer): Subjects with breast cancer that is hormone receptor-positive (estrogen receptor positive [ER+] and/or progesterone receptor positive [PR+]) and negative for human epidermal growth factor receptor 2 (HER-2 negative [HER-2-]) and who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
  • Dose-Escalation Stage Cohort C and Cohort-Expansion Stage Cohorts G and I (Metastatic Castration-Resistant Prostate Cancer): Subjects with adenocarcinoma of the prostate. Note: Neuroendocrine differentiation and other histological features are permitted if adenocarcinoma is the primary histology.
  • Cohort-Expansion Stage Cohort D (Triple Negative Breast Cancer): Subjects with breast cancer that is negative for HER-2, estrogen receptors, and progesterone receptors, and who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
  • Cohort-Expansion Stage Cohort E (Epithelial Ovarian Cancer): Subjects with epithelial ovarian cancer, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC) who have platinum-resistant disease following treatment with a platinum-containing chemotherapy. Ovarian borderline epithelial tumors (low malignant potential) are excluded.
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  • Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1 as determined by the Investigator.
  • Tumor tissue material (archival or fresh tumor tissue [if it can be safely obtained]).
  • Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs, unless AEs are clinically nonsignificant (eg, alopecia) or stable (eg, peripheral neuropathy).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  • Adequate organ and marrow function.
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
  • Female subjects of childbearing potential must not be pregnant at screening.

Who cannot join

  • Receipt of XL102 or any other selective CDK7 inhibitor.
  • Receipt of any cytotoxic chemotherapy therapy or anticancer antibody therapy within 21 days before first dose of study treatment.
  • Receipt of any type of small molecule kinase inhibitor within 2 weeks before first dose of study treatment.
  • Receipt of any anticancer hormonal therapy within 2 weeks or within 5 half-lives of the agent, whichever is shorter, before first dose of study treatment. HR+BC subjects enrolled in the Combination Cohorts B and H receiving fulvestrant prior to first dose of study treatment are allowed to continue with their fulvestrant treatment. Metastatic CRPC subjects enrolled in the Combination Cohorts C and I receiving abiraterone prior to first dose of study treatment are allowed to continue with their abiraterone treatment.
  • Radiation therapy within 14 days before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Known brain tumors and metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
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  • Use of strong inhibitors or inducers of cytochrome P450 (CYP) 3A4, and inhibitors of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) transporter within 5 half-lives or 4 weeks prior to first dose of study treatment, whichever is shorter.
  • Use of a sensitive substrate of CYP3A4, CYP2B6, CYP2C8, CYP2C9, or BCRP transporter within 5 half-lives or 4 weeks prior to first dose of study treatment, whichever is shorter. For subjects with mCRPC in receiving combination treatment with XL102 and abiraterone plus prednisone, use of a substrate of CYP2D6 with a narrow therapeutic index within 5 half-lives or 4 weeks prior to first dose of study treatment, whichever is shorter, is prohibited.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders: i. congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, torsades de pointes). ii. uncontrolled hypertension defined as sustained blood pressure > 150 mmHg systolic or >90 mm Hg diastolic despite optimal antihypertensive treatment. iii. stroke (including transient ischemic attack [TIA]), myocardial infarction, or other ischemic event or pulmonary embolism (PE) within 6 months before first dose. Note: Subjects with a diagnosis of deep vein thrombosis (DVT) within 6 months before first dose are allowed if managed adequately with anticoagulants and asymptomatic at the time of first dose.
  • history of any lower gastrointestinal (GI) disorder (such as inflammatory bowel disease [IBD]) or any form of colitis (such as ulcerative colitis or Crohn's disease).
  • history of upper gastrointestinal (GI) inflammatory disorder (eg, esophagitis, gastritis, or duodenitis), gastroparesis, symptomatic gastroesophageal reflux disease (GERD) despite medical therapy, or gastric or duodenal ulcers within 6 months.
  • history of major surgical resection involving the stomach or small bowel or any other reason for a malabsorption syndrome.
  • history of significant bleeding (eg, GI hemorrhage) within 12 weeks before first dose.
  • active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, acute or chronic hepatitis B or C infection, or a known positive test for tuberculosis infection if supported by clinical or radiographic evidence of disease. Prophylactic use of antibiotics is allowed.
  • History of COVID-19 unless the subject has clinically recovered from the infection: at least 10 days prior to first dose or sooner, if COVID-19 PCR negative.
  • moderate to severe hepatic impairment (child-pugh B or C)
  • requirement for hemodialysis or peritoneal dialysis
  • history of solid organ, autologous or allogenic stem cell transplant
  • Concomitant use of certain medications.
  • Uncontrolled, significant intercurrent or recent illness.
  • Major surgery within 4 week before first dose of treatment. Minor surgery within 7 days before first dose of treatment. Complete wound healing from surgery must have occurred before first dose of treatment.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG).
  • History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
  • Inability to swallow oral study treatment formulation
  • Previously identified allergy or hypersensitivity to study treatment formulation
  • Pregnant or lactating females.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
  • For subjects in Food-Effect Cohorts (A-FE) only: i. Known inability to tolerate high-fat meal provided on Day 1 ii. Allergy to meal components or dietary restrictions iii. Unable to fast for 4 hours predose and 2 hours post dose on Day 8

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Exelixis Clinical Site #4

    Atlanta, Georgia, 30322

  • Exelixis Clinical Site #3

    Boston, Massachusetts, 02215

  • Exelixis Clinical Site #2

    Dallas, Texas, 75230

  • Exelixis Clinical Site #5

    Houston, Texas, 77030

  • Exelixis Clinical Site #1

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Dose Escalation and Expansion Study of the Safety and Pharmacokinetics of XL102 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors

This is a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, PK, antitumor activity, and effect on biomarkers of XL102 administered orally alone and in multiple combination regimens to subjects with advanced solid tumors.

Being tested
XL102, Fulvestrant, Abiraterone, Prednisone
Keywords
cdk7 inhibitor
Medical subject headings
Neoplasms, Carcinoma, Ovarian Epithelial, Triple Negative Breast Neoplasms

What participants receive

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

  • XL102Drug

    oral doses of XL102

  • FulvestrantDrug

    fulvestrant 500 mg administered as an intramuscular (IM) injection every 2 weeks for the first 3 doses and then every 4 weeks.

  • AbirateroneDrug

    abiraterone 1000 mg administered orally once daily.

  • PrednisoneDrug

    prednisone 5 mg administered orally twice daily.

Study groups in NCT04726332
Study groupRoleWhat they receive
XL102 Single-Agent Dose-Escalation CohortsExperimentalSubjects will be separated into three separate groups of cohorts. Formulation A consists of: Fasted, with approximately 9 cohorts (A-FC) starting at 20 mg (qd and/or bid) of XL102, Food-Effect Dose-Escalation at 40 mg qd of XL102, with approximately 3 cohorts (A-FE) and Non-Fasted, with approximately 6 cohorts (A-NF). Formulation B consists of additional cohorts: Fasted (A-FCFB) starting at 40 mg (qd and/or bid) of XL102 and Non-Fasted (A-NFCFB). The dose of the remaining A-FE cohorts will be determined by the Cohort Review Committee (CRC) as well as that of the A-NF, and A-NFCFB cohorts.
Receives: Drug: XL102
XL102 Single-Agent Expansion CohortsExperimentalThe Maximum Tolerated Dose (MTD) or recommended dose from the dose-escalation stage may be further explored in subjects with triple-negative breast cancer (TNBC) (Cohort D), epithelial ovarian cancer (EOC) (Cohort E), hormone receptor-positive breast cancer (HR+ BC) (Cohort F), and metastatic castration-resistant prostate cancer (mCRPC) (Cohort G).
Receives: Drug: XL102
XL102 + Fulvestrant Dose-Escalation CohortsExperimentalSubjects with HR+ BC (Cohort B) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
Receives: Drug: XL102; Drug: Fulvestrant
XL102 + Abiraterone/Prednisone Dose-Escalation CohortsExperimentalSubjects with mCRPC (Cohort C) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
Receives: Drug: XL102; Drug: Abiraterone; Drug: Prednisone
XL102 + Fulvestrant Expansion CohortsExperimentalThe MTD or recommended dose from the dose-escalation stage may be further explored in subjects with HR+ BC (Cohort H).
Receives: Drug: XL102; Drug: Fulvestrant
XL102 + Abiraterone/Prednisone Expansion CohortsExperimentalThe MTD or recommended dose from the dose-escalation stage may be further explored in subjects with mCRPC (Cohort I).
Receives: Drug: XL102; Drug: Abiraterone; Drug: Prednisone

What is being measured

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

  1. Dose-Escalation Stage: MTD/recommended dose for XL102

    To determine the MTD and/or RD for further evaluation of XL102 when administered orally alone and in combination therapy in subjects with advanced solid tumors

    Measured: Approximately 18 months

  2. Cohort-Expansion Stage: Objective Response Rate (ORR)

    To evaluate preliminary efficacy of XL102 when administered alone and in combination therapy by estimating the ORR as assessed by the Investigator per RECIST 1.1

    Measured: Approximately 12 months

Secondary outcomes (8)

  1. Safety of XL102 as evaluated by Incidence and Severity of Adverse Events (AEs)

    To evaluate the safety of XL102 when administered orally alone and in combination therapy through the evaluation of overall incidence of AEs, severity grade, relationship to study treatment, and laboratory tests.

    Measured: Approximately 30 months

  2. Tolerability of XL102 as evaluated by Study Treatment Exposure, Dose Intensity and Modifications, and Study Treatment Discontinuation due to AE

    To evaluate the tolerability of XL102 when administered orally alone and in combination therapy through the evaluation of study treatment exposure, dose intensity, dose modifications, and study treatment discontinuation due to AE.

    Measured: Approximately 30 months

  3. Dose-Escalation Stage: Drug-Drug Interactions

    To assess drug-drug interactions between XL102 and combination agents

    Measured: Approximately 18 months

  4. Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)

    To evaluate the Tmax of XL102 alone and in combination therapy

    Measured: Approximately 18 months

  5. Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)

    To evaluate the Cmax of XL102 alone and in combination therapy

    Measured: Approximately 18 months

  6. Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)

    To evaluate the AUC 0-24 of XL102 alone and in combination therapy

    Measured: Approximately 18 months

  7. Dose-Escalation Stage: Terminal Half-Life

    To evaluate the terminal half-life of XL102 alone and in combination therapy

    Measured: Approximately 18 months

  8. Dose-Escalation Stage: Apparent Clearance (CL/F)

    To evaluate the CL/F of XL102 alone and in combination therapy

    Measured: Approximately 18 months

Timeline

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

  1. First posted27 Jan 2021
  2. Study start10 Feb 2021
  3. Primary completion2 May 2024
  4. Study completion2 May 2024

Why it stopped: Business reasons

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
Sequential
Model description
Single-agent and combination therapy dose-escalation followed by cohort-expansion
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04726332
Sponsor's protocol ID
XL102-101
Status last verified
May 2024
First submitted
22 Jan 2021
Last updated
14 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Gaur T, Poddutoori R, Khare L, Bagal B, Rashmi S, Patkar N, Tembhare P, Pg S, Shetty D, Dutt A, Zhang Q, Konopleva M, Platzbeckar U, Gupta S, Samajdar S, Ramchandra M, Khattry N, Hasan SK. Novel covalent CDK7 inhibitor potently induces apoptosis in acute myeloid leukemia and synergizes with Venetoclax. J Exp Clin Cancer Res. 2023 Jul 29;42(1):186. doi: 10.1186/s13046-023-02750-w.

    PubMed 37507802

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing XL102, Fulvestrant and Abiraterone in people with Neoplasm Malignant and Epithelial Ovarian Cancer, run by Exelixis at 5 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 13 inclusion and 29 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 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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: Business reasons). 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?

Dose-Escalation Stage: MTD/recommended dose for XL102 (time frame: Approximately 18 months). 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 NCT04726332, which also lists 1 linked publication.

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 14 May 2024.

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