We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    SER-ISD1-001
Previous Study | Return to List | Next Study

Combination of Serabelisib and Insulin Suppressing Diet With or Without Nab-paclitaxel in Subjects With Advanced Solid Tumors With PIK3CA Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05300048
Recruitment Status : Recruiting
First Posted : March 29, 2022
Last Update Posted : August 26, 2022
Sponsor:
Information provided by (Responsible Party):
Faeth Therapeutics

Brief Summary:
This study will evaluate the feasibility of optimizing the safety and tolerability of serabelisib (an investigational PI3K inhibitor) when combined with an ISD and with or without nab-paclitaxel with a goal of reducing side effects and enhancing anticancer activity.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor PIK3CA Mutation PTEN Loss of Function Mutation Drug: Serabelisib Other: Insulin Suppressing Diet Drug: Nab paclitaxel Phase 1

Detailed Description:
Targeted anticancer drugs have side effects that often result in a poor quality of life, noncompliance, dose decreases, or discontinuation, all of which can affect efficacy. This study will evaluate the feasibility of optimizing the safety and tolerability of serabelisib when combined with an insulin suppressing diet and with or without nab-paclitaxel with a goal of reducing side effects and enhancing anticancer activity.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Serabelisib in Combination With an Insulin Suppressing Diet (Study ISD) and With or Without Nab-paclitaxel in Adult Subjects With Advanced Solid Tumors With PIK3CA Mutations With or Without PTEN Loss
Actual Study Start Date : April 22, 2022
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1a - Dose Modification without nab-paclitaxel
Subjects with any solid tumor will receive multiple doses of serabelisib administered orally and will consume Insulin Suppressing Diet for up to 12 months
Drug: Serabelisib
serabelisib administered orally

Other: Insulin Suppressing Diet
3 meals consumed daily (i.e., breakfast, lunch, dinner) and optional snacks provided dependent on caloric needs

Experimental: Cohort 1b - Dose Modification with Nab-Paclitaxel
Subjects with endometrial cancer, ovarian clear cell or ovarian endometrial carcinoma will receive multiple doses of serabelisib administered orally and will consume Insulin Suppressing Diet for up to 12 months. In addition, these subjects will receive nab-paclitaxel intravenously weekly.
Drug: Serabelisib
serabelisib administered orally

Other: Insulin Suppressing Diet
3 meals consumed daily (i.e., breakfast, lunch, dinner) and optional snacks provided dependent on caloric needs

Drug: Nab paclitaxel
nab-paclitaxel administered intravenously weekly

Experimental: Cohort 2 - Expansion Colorectal Cancer
Subjects will receive dose of serabelisib as determined from Cohort 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months
Drug: Serabelisib
serabelisib administered orally

Other: Insulin Suppressing Diet
3 meals consumed daily (i.e., breakfast, lunch, dinner) and optional snacks provided dependent on caloric needs

Experimental: Cohort 3 - Expansion Endometrial Cancer
Subjects will receive dose of serabelisib as determined from Cohort 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months. If results from Cohort 1b show a favorable risk-benefit ratio, nab-paclitaxel will be administered intravenously weekly.
Drug: Serabelisib
serabelisib administered orally

Other: Insulin Suppressing Diet
3 meals consumed daily (i.e., breakfast, lunch, dinner) and optional snacks provided dependent on caloric needs

Drug: Nab paclitaxel
nab-paclitaxel administered intravenously weekly

Experimental: Cohort 4 - Expansion Ovarian Clear Cell or Ovarian Endometrioid Carcinoma
Subjects will receive dose of serabelisib as determined from Cohorts 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months. If results from Cohort 1b show a favorable risk-benefit ratio, nab-paclitaxel will be administered intravenously weekly.
Drug: Serabelisib
serabelisib administered orally

Other: Insulin Suppressing Diet
3 meals consumed daily (i.e., breakfast, lunch, dinner) and optional snacks provided dependent on caloric needs

Drug: Nab paclitaxel
nab-paclitaxel administered intravenously weekly




Primary Outcome Measures :
  1. Cohorts 1a/1b: Evaluate safety [ Time Frame: Through study completion, up to 12 months. ]
    Incidence of related AEs

  2. Cohorts 1a/1b: Evaluate compliance [ Time Frame: Through study completion, up to 12 months. ]
    Compliance of Study intervention

  3. Cohorts 1a/1b: Evaluate the pharmacokinetic impact by measuring Cmax. [ Time Frame: Through study completion, up to 12 months. ]
    Standard pharmacokinetic parameters (Cmax)

  4. Cohorts 1a/1b: Evaluate the pharmacokinetic impact by measuring Tmax. [ Time Frame: Through study completion, up to 12 months. ]
    Standard pharmacokinetic parameters (Tmax).

  5. Cohorts 1a/1b: Evaluate the pharmacokinetic impact by measuring AUC. [ Time Frame: Through study completion, up to 12 months. ]
    Standard pharmacokinetic parameters (AUC).

  6. Cohorts 2, 3, 4: Use the Objective Response Rate (ORR) to assess the antitumor efficacy of serabelisib in combination with a Study ISD. [ Time Frame: Through study completion, an average of 8 months. ]
    Proportion of subjects who have best overall response of either complete response (CR) or partial response (PR)


Secondary Outcome Measures :
  1. Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring ORR. [ Time Frame: Through study completion, up to 12 months. ]
    Proportion of subjects who have best overall response of either CR or PR, as determined by each site.

  2. Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring PFS. [ Time Frame: Through study completion, up to 12 months. ]
    Time from date of first dose of Study Drug (Visit 1) to the date of first evidence of disease progression or death from any cause (whichever occurs first).

  3. Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring OS. [ Time Frame: Through study completion, up to 12 months. ]
    Overall survival (OS) and landmark survival.

  4. Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring DoR. [ Time Frame: Through study completion, up to 12 months. ]
    Duration of response (DoR) Disease control rate (DCR; CR + PR + stable disease [SD])

  5. Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring DCR. [ Time Frame: Through study completion, up to 12 months. ]
    Disease control rate (DCR; CR + PR + stable disease [SD])

  6. Cohort 2, 3, 4: Confirm safety [ Time Frame: Through study completion, up to 12 months. ]
    Incidence of related AEs

  7. Cohort 2, 3, 4: Confirm the compliance of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Compliance of Study intervention

  8. Cohort 2, 3, 4: Additional assessments of antitumor efficacy of study intervention (Measuring PFS). [ Time Frame: Through study completion, up to 12 months. ]

    Time from the date of first dose of Study Drug (Visit 1) to the date of first evidence of disease progression or death from any cause (whichever occurs first)

    DoR DCR (CR+PR+SD)


  9. Cohort 2, 3, 4: Additional assessments of antitumor efficacy of study intervention (Measuring OS). [ Time Frame: Through study completion, up to 12 months. ]
    OS and landmark survival

  10. Cohort 2, 3, 4: Additional assessments of antitumor efficacy of study intervention (Measuring DoR). [ Time Frame: Through study completion, up to 12 months. ]
    DoR

  11. Cohort 2, 3, 4: Additional assessments of antitumor efficacy of study intervention (Measuring DCR). [ Time Frame: Through study completion, up to 12 months. ]
    DCR (CR+PR+SD)

  12. Cohort 2, 3, 4: Assess the population PK and intra-tumoral concentration of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Standard PK Parameters (Cmax) in plasma.

  13. Cohort 2, 3, 4: Assess the population PK and intra-tumoral concentration of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Standard PK Parameters (Tmax) in plasma

  14. Cohort 2, 3, 4: Assess the population PK and intra-tumoral concentration of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Standard PK Parameters (AUC) in plasma

  15. Cohort 2, 3, 4: Assess the population PK and intra-tumoral concentration of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Serabelisib concentration in tumor tissue


Other Outcome Measures:
  1. Cohorts 1a/1b, 2, 3, 4: Assessment of PD of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Change in PD markers (insulin)

  2. Cohorts 1a/1b, 2, 3, 4: Assessment of PD of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Change in PD markers (glucose)

  3. Cohorts 1a/1b, 2, 3, 4: Assessment of PD of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Change in biomarkers of insulin-PI3K signaling

  4. Cohorts 1a/1b, 2, 3, 4: Assessment of PD of study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Changes in tumor marker levels.

  5. Cohorts 1a/1b, 2, 3, 4: Assessment of immune markers in response to study intervention. [ Time Frame: Through study completion, up to 12 months. ]
    Assessment of immune markers in PBMCs throughout study.

  6. Cohorts 1a/1b, 2, 3, 4: Assessment of genetic predictors of efficacy. [ Time Frame: Through study completion, up to 12 months. ]
    Analysis into whether the genetic status of the patient predicts a positive or negative therapeutic response (efficacy).

  7. Cohorts 1a/1b, 2, 3, 4: Assessment of genetic predictors of toxicity. [ Time Frame: Through study completion, up to 12 months. ]
    Analysis into whether the genetic status of the patient predicts susceptibility to AEs (toxicity).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to provide written informed consent.
  2. Age ≥18 at Visit -1 (screening).
  3. Histologically or cytologically confirmed recurrent solid tumors.

    1. Cohort 1a: any extracranial solid tumor
    2. Cohort 1b: either recurrent or persistent endometrial adenocarcinoma (EC) with the following histologic epithelial cell types: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, transitional cell carcinoma, and carcinosarcoma or; ovarian cancer (OC) with the primary tumor having ≥ 50% clear cell histomorphology or ovarian clear cell or ovarian endometrioid carcinoma.
    3. Cohort 2: adenocarcinoma of the colon or rectum.
    4. Cohort 3: recurrent or persistent endometrial adenocarcinoma with the following histologic epithelial cell types as described for Cohort 1b
    5. Cohort 4: OC primary tumor carcinomas as described for Cohort 1b
  4. Tumor must harbor an activating mutation in the PIK3CA gene with or without PTEN loss, either previously documented or determined during screening.
  5. Fresh or archival tumor biopsy with sufficient material to be sent to the designated laboratory for PD analyses. For patients who consent to future research, an additional 5 slides from a surgical specimen or biopsy is required.
  6. Cohort 1a - Dose Modification (subjects with any solid tumor): failed, were intolerant of, or ineligible for no more than 3 prior lines of therapy (LOT) for advanced/metastatic disease or refused SOC therapy.
  7. For all cohorts, in the unlikely scenario that a subject refused all available SOC they may proceed with trial. These subjects would be regarded as having 0 prior LOT.
  8. Cohorts 1b, 2, 3, and 4 - failed, were intolerant of, ineligible for, or have refused SOC therapy for advanced/metastatic disease (AJCC stage III and IV) and:

    1. Cohort 2 (subjects with colorectal cancer): Have failed no more than 2 prior LOT for metastatic CRC.
    2. Cohort 1b, Cohort 3 (subjects with endometrial cancer): Have no more than 3 prior chemotherapeutic regimens for management of endometrial carcinoma (neo-adjuvant and/or adjuvant chemotherapy will be counted as 1 prior LOT). Prior hormonal therapy will not count as a systemic regimen.
    3. Cohort 1b, Cohort 4 (subjects with clear cell or endometrioid OC): Subjects must have had no more than 3 prior chemotherapeutic regimens for management of ovarian carcinoma. Prior hormonal therapy will not count as a systemic regimen.
  9. Life expectancy of at least 3 months.
  10. At least one measurable lesion (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
  11. ECOG PS of 0 to 1.
  12. Adequate organ function

    1. Absolute neutrophil count (ANC) ≥1.0 × 10^9/L, platelet count ≥75 × 10^9/L, and hemoglobin ≥8.5 gm/dL (may be transfused to reach this hemoglobin level unless due to blood loss).
    2. Liver transaminases (AST and ALT) ≤2.5 × upper limit of normal (ULN) (<5 × ULN if liver metastases are present), and total bilirubin ≤1.5 × ULN (<3 x ULN if subject has Gilbert Syndrome).
    3. INR ≤1.5 x ULN unless subject is on anticoagulants that would affect the INR, then INR must be in the desired therapeutic range as judged by the Investigator.
    4. Albumin level ≥3.0 mg/dL or ≥ the lower limit of normal.
    5. Renal: Serum creatinine ≤2 x ULN
  13. Ability to take oral medication, be willing to adhere to study procedures and Study Drug administration, and receive, consume, and comply with Study ISD.
  14. For women of child-bearing potential, a negative serum pregnancy test collected at screening (V-1) and negative urine pregnancy test collected at baseline (V0) and use of physician-approved method of birth control from the time of the pregnancy test performed at screening to 90 days following the last administration of Study Drug.
  15. Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 90 days following the last administration of Study Drug.

Exclusion Criteria:

  1. Diagnosis of primary brain tumor.
  2. Has had serabelisib, alpelisib, or other PI3K inhibitor.
  3. Leptomeningeal disease and symptomatic or untreated brain metastases.
  4. Diagnosis of, or requiring treatment for, another malignancy within the past 2 years (excluding a history of carcinoma in situ of the cervix, superficial non-melanoma skin cancer, or superficial bladder cancer that has been adequately treated, or stage 1 prostate cancer that does not require treatment or requires only treatment with luteinizing hormone-releasing hormone agonists or antagonists if initiated at least 90 days prior to the first dose of Study Drug).
  5. Is less than 21 days from therapeutic radiation or chemotherapy prior to the first day of dosing with Study Drug and has not recovered to Grade ≤ 1 from all clinically significant toxicities related to prior therapies.
  6. For subjects receiving nitrosoureas or mitomycin C, the subject is < 6 weeks from last dose. For monoclonal antibody therapy, the subject is < one half-life or <4 weeks from the last dose.
  7. Chronic, systemically administered glucocorticoids in doses equivalent to >5 mg prednisone daily. Replacement corticosteroids for adrenal insufficiency are permitted.
  8. Diabetes mellitus requiring insulin or insulin secretagogue therapy.
  9. Poorly controlled diabetes mellitus defined as glycosylated hemoglobin A1c (HbA1c) >7.5% or fasting blood sugar >160 mg/ dL.
  10. Known impaired cardiac function or clinically significant cardiac disease.
  11. QTcF interval >470 msec found at screening.
  12. Myocardial infarction, cardiac stent placement, or unstable angina within 6 months before the first administration of Study Drug.
  13. Have clinically significant peripheral vascular disease.
  14. Manifestations of malabsorption
  15. Other clinically significant comorbidities.
  16. Pregnant (positive serum pregnancy test), planning to become pregnant during the study, or breastfeeding/planning to breastfeed during the study.
  17. Have taken strong CYP3A4 inducers/inhibitors within 7 days before the first administration of serabelisib or have conditions that require the concomitant use of CYP3A4 inducers/inhibitors.
  18. Untreated or poorly controlled, gastro-esophageal reflux disease.
  19. Have taken histamine-H2 receptor antagonists within 24 hours before the first administration of serabelisib.
  20. Have taken PPI within 7 days or 5 half-lives (whichever is the shorter duration) before the first administration of serabelisib or are anticipated to need PPI during the study.
  21. Have taken neutralizing antacids within 4 hours before the first administration of serabelisib or are anticipated to need frequent antacid use during the study.
  22. Subjects with poorly controlled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infections.
  23. Known allergies to serabelisib excipients or the ISD
  24. Severe, uncontrolled gout.
  25. A BMI <18.5 kg/m2, or serious or refractive cachexia or anorexia that, in the Investigator's opinion, realistically prohibits subjects from having energy or appetite sufficient to reliably engage in a strict medical food regimen for an extended time.
  26. Any condition that renders the subject unable to satisfactorily chew, swallow, digest, or tolerate (i.e., persistent diarrhea) the majority of foods and liquids of the Study ISD.
  27. History of severe nephrolithiasis requiring urologic intervention.
  28. Participation in a diet or weight loss plan within 10 days prior to the first administration of Study Drug.
  29. Severe constipation or condition where exacerbation of constipation is not advisable (eg, small bowel obstruction history).
  30. History of anaphylaxis from food allergy or other disease state requiring avoidance of a particular food, such as celiac disease.
  31. Diagnosed eating disorder in the past 10 years.
  32. Unwilling to take a non-vegan or non-vegetarian diet.
  33. Peripheral neuropathy ≥ CTC Grade 2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05300048


Contacts
Layout table for location contacts
Contact: Study Inquiry (650) 488-1109 clinicaltrials@faeththerapeutics.com

Locations
Layout table for location information
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35429
Contact: Jill Hyde    205-975-2362    jspratlin@uabmc.edu   
United States, California
Pacific Cancer Specialists Recruiting
Anaheim, California, United States, 92801
Contact: Elizabeth Brown    714-999-1465    elizabethg@pacificcancer.com   
Women's Cancer Research Network Not yet recruiting
Fresno, California, United States, 93710
Contact: Trevor Frosig    855-438-7535    trevorfrosig@theoncologyinstitute.com   
Hoag Memorial Hospital Presbyterian Recruiting
Newport Beach, California, United States, 92663
Contact: Leila Andres    949-764-8092    Leila.Andres@hoag.org   
Contact: Ryan Helber    949-764-4430    Ryan.Helber1@hoag.org   
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Clinical Research Staff    773-702-1000    cancerclinicaltrials@bsd.uchicago.edu   
United States, Minnesota
Mayo Clinic - Rochester Not yet recruiting
Rochester, Minnesota, United States, 55902
Contact: Recruitment Hotline    855-776-0015    MAYOCLINICCANCERSTUDIES@mayo.edu   
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Vickie Makker    646-888-4224    makkerv@mskcc.org   
United States, North Carolina
East Carolina University Not yet recruiting
Greenville, North Carolina, United States, 27858
Contact: Hematology Oncology Clinical Trials Office    252-816-2273    hemoncclinicaltrials@ecu.edu   
United States, South Dakota
Avera Cancer Institute Recruiting
Sioux Falls, South Dakota, United States, 57105
Contact: David Starks    605-322-7535    david.starks@avera.org   
United States, Texas
University of Texas Southwestern Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Martha Cruz    214-648-7097    martha.cruz@utsw.edu   
United States, Wisconsin
Medical College of Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Clinical Trials Office    414-805-6800    cccto@mcw.edu   
Sponsors and Collaborators
Faeth Therapeutics
Investigators
Layout table for investigator information
Principal Investigator: Vicky Makker Memorial Sloan Kettering Cancer Center
Layout table for additonal information
Responsible Party: Faeth Therapeutics
ClinicalTrials.gov Identifier: NCT05300048    
Other Study ID Numbers: SER-ISD1-001
First Posted: March 29, 2022    Key Record Dates
Last Update Posted: August 26, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Faeth Therapeutics:
PIK3CA Mutation
PTEN Loss of Function Mutation
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Paclitaxel
Serabelisib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors