A Study Evaluating the Safety and Effectiveness of Therapies in Patients with Metastatic Colorectal Cancer

Overview

About this study

The purpose of this study for the Inavo + Cetux Arm:  To evaluate the effectiveness of Inavo + Cetux in PIK3CA-mutated colorectal cancer (CRC) with no detected RAS (KRAS, NRAS) or BRAFV600E mutations.

The purpose of this study for the Inavo + Bev Arm:  To evaluate the effectiveness Inavo + Bev in PIK3CA-mutated, RAS (KRAS, NRAS)-mutated CRC.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - Biomarker Eligibility Testing:

  • Signed NGS Biomarker Eligibility Informed Consent Form.
  • Age ≥ 18 years at the time of signing Informed Consent Form.
  • Full report of prior testing results (if available) that does not meet screening criteria.

Inclusion Criteria - Screening:

  • For patients with a positive biomarker status: Signed NGS Biomarker Eligibility Informed Consent Form and signed treatment arm-specific Informed Consent Form.
  • Biomarker eligibility (per treatment arm-specific definition) as determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory using a validated test based on: Prior test result and availability of a full report of the testing results OR Blood-based FoundationOne Liquid CDx biomarker eligibility test result generated prior to or during screening or in case of re-enrollment after treatment discontinuation prior to starting a new anti-cancer therapy.
  • Age ≥ 18 years at the time of signing Informed Consent Form.
  • ECOG Performance Status of ≤ 1.
  • Life expectancy ≥ 3 months, as determined by the investigator.
  • Histologically confirmed adenocarcinoma originating from the colon or rectum.
  • Metastatic disease (Stage IV American Joint Committee on Cancer, Version 7).
  • Prior therapies for metastatic disease: Refer to the respective treatment arm-specific appendix as criteria for prior therapies may vary between treatment arms.
  • Ability to comply with the study protocol, in the investigator’s judgment.
  • Measurable disease (at least one target lesion) according to RECIST v1.1.
    • Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
  • Availability of an archival tissue sample for exploratory biomarker research. 
    • If no tissue is available, the patient may be eligible after discussion with the Medical Monitor.
  • Adequate hematologic and organ function within 14 days prior to initiation of study treatment, defined by the following:
    • Absolute neutrophil count ≥ 1500/µL without granulocyte colony-stimulating factor;
    • WBC count ≥ 2.5 x 10^9 /L (2500/µL);
    • Lymphocyte count ≥ 0.5 x 10^9 /L (500/L);
    • Platelet count ≥ 100,000/µL;
    • Hemoglobin ≥ 9 g/dL.
    • Patients must not have been transfused within 2 weeks prior to screening to meet this criterion.
  • Total bilirubin ≤ 1.5 x  upper limit of normal (ULN) (≤ 3 x ULN if Gilbert’s disease).
  • Serum albumin ≥ 2.8 g/dL or 28 g/L.
  • AST and ALT ≤ 2.5 x ULN with the following exception:
    • Patients with documented liver metastases may have AST and/or ALT ≤ 5.0 x ULN.
  • ALP ≤ 2.5 x ULN with the following exception:
    • Patients with documented liver or bonen: INR ≤ 1.5 xULN and aPTT ≤ 1.5 x ULN.
  • Creatinine clearance ≥ 50 mL/min (calculated through use of the Cockcroft-Gault formula) or creatinine ≤ 1.5 x ULN.
  • For patients not receiving therapeutic anticoagulation: INR ≤ 1.5 x ULN and aPTT ≤  1.5 x ULN.

Exclusion Criteria:

  • Current participation or enrollment in another interventional clinical trial.
  • Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment.
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment.
    • Note: For re-enrollment in a different treatment arm after study treatment discontinuation, the investigator and Medical Monitor will discuss the timepoint (Day 1 of Cycle 1) for initiation of study treatment which may be shorter than 28 days since the last dose of prior study treatment.
  • Pregnant or breastfeeding, or intending to become pregnant during the study.
  • For women of childbearing potential: Must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined in treatment arm-specific appendix.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined in the treatment arm-specific appendix.
  • History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study.
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety.
  • Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
  • Use of an in-dwelling catheter (e.g., PleurX® ) is allowed.
  • Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be evaluated for loco-regional therapy, if appropriate, prior to enrollment.
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium 12 mg/dL, or corrected serum calcium > ULN).
  • Clinically significant and active liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
  • Known HIV infection.
    • Sites should include an HIV test during screening, as allowed per local regulations.
  • Symptomatic, untreated, or actively progressing CNS metastases.
  • Patients with a history of treated CNS metastases are eligible provided that all of the following criteria are met:
    • Measurable disease, per RECIST v1.1, must be present outside the CNS;
    • The patient has no history of intracranial hemorrhage or spinal cord hemorrhage;
    • Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord);
    • There is no evidence of interim progression between completion of CNS-directed therapy and the screening brain scan;
    • The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment;
    • The patient has no ongoing requirement for corticosteroids as therapy for CNS disease;
    • If the patient is receiving anti-convulsant therapy, the dose is considered stable;
    • Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
  • History of leptomeningeal disease or carcinomatous meningitis.
  • History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
  • Any other disease, unresolved toxicity from prior therapy, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
  • Requirement for treatment with any medicinal product that contraindicates the use of any of the study treatments, may interfere with the planned treatment, affects patient compliance, or puts the patient at higher risk for treatment-related complications.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Joleen Hubbard, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Tanios Bekaii-Saab, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Jeremy Jones, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
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CLS-20521138

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