This study is currently recruiting participants.
Number
001771-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 100 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Pregnant Women
Keywords
Precision Medicine; Combination Therapy; mutation of interest
Recruitment Keyword(s)
None
Condition(s)
Solid Tumors
Investigational Drug(s)
GDC-0068
Investigational Device(s)
Intervention(s)
Drug: Ipatasertib Drug: Paclitaxel
Supporting Site
National Cancer Institute
Many types of cancers develop in people who have gene mutations that make it more difficult for their bodies to fight tumors. Some drugs work against these cancers because they counter the effects these gene mutations have in the body. Researchers want to find out if a new drug (ipatasertib) can help fight cancer in people with mutations in a specific gene (AKT).
Objective:
To test a study drug (ipatasertib) combined with paclitaxel in people with tumors that have AKT gene mutations. (Paclitaxel is approved for the treatment of cancers.)
Eligibility:
People with cancer with an AKT mutation; they must be enrolled in the ComboMATCH Master Registration Trial EAY191.
Design:
Participants will be screened. They will have blood tests. They may need a new biopsy: A small piece of tissue will be removed from the tumor.
Participants will be treated in 28-day cycles.
Paclitaxel is given through a tube attached to a needle inserted in a vein in the arm. Participants will receive paclitaxel once a week for the first 3 weeks of each cycle.
Ipatasertib is a pill taken by mouth. Participants will take the pill once a day for the first 21 days of each cycle. They will keep a diary to write down when they take the pills.
Blood tests will be repeated during study visits.
Participants will continue treatment as long as the drugs are helping them.
Follow-up visits may continue for up to 3 years after the start of treatment. These follow-ups may be by phone or in the clinic.
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ELIGIBLITY CRITERIA: All criteria below refer to registrations to this sub-protocol EAY191-S3, unless otherwise specified. 1. General ComboMATCH EAY191 Registration Criteria a. Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191. b. Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or AKT3, a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment. c. Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment. d. Participants must have disease that can be safely biopsied and agree to a pre- treatment biopsy or have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191). 2. Disease Related Criteria a. Participants must have a histologically confirmed non-breast solid malignancy. b. Participants must have locally advanced, unresectable, or metastatic disease in the opinion of the treating investigator. c. Participants must have measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to registration. Non- measurable disease must be assessed within 42 days prior to registration. The CT from a combined PET/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration. d. Participants with known brain metastases must have a CT/MRI scan to evaluate for CNS disease and show no evidence of progression within 42 days prior to registration. e. Participants must have completed any CNS-directed therapy and/or local therapy for spinal cord compression at least 28 days prior to registration. f. Participants must not have spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days prior to registration, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to registration. g. Participants must not have leptomeningeal disease 3. Prior/Concurrent Therapy Criteria a. Participants must have progressed within 6 months of taxane-based therapy in the neoadjuvant/adjuvant or metastatic setting. b. Participants must not have received any prior AKT inhibitor (e.g., capivasertib or ipatasertib); prior PI3K/mTOR inhibitor is acceptable. c. Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while receiving treatment on this study. 4. Clinical/Laboratory Criteria a. Participants must be >= 18 years of age. b. Participants must be able to swallow oral medications whole. c. Participants must have a pre-study history and physical exam done within 28 days prior to registration. d. Participants must have a Zubrod performance status of 0-2 within 28 days prior to registration. e. Participants must have adverse events resolved <= Grade 1 related to any prior therapy, except alopecia within 14 days prior to registration. f. Participants with neuropathy must have resolved to < Grade 2 within 14 days prior to registration. g. Participants must have adequate organ and marrow function within 28 days prior to registration as defined below: leukocytes >= 3 x 10^3/uL absolute neutrophil count >= 1.5 x 10^3/uL platelets >= 100 x 10^3/uL total bilirubin <= institutional upper limit of normal (ULN) unless history of Gilbert s disease. Participants with history of Gilbert s disease must have total bilirubin <= 5 x institutional ULN. AST & ALT <= 3 x institutional ULN h. Participants must have adequate cardiac function, class IIB (2B) or better. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. i. Participants must have a measured OR calculated creatinine clearance >= 50 mL/min using the following Cockroft-Gault Formula. This specimen must have been drawn within 28 days prior to registration: Calculated Creatinine Clearance = (140 - age) X (weight in kg)**/72 x serum creatinine * Multiply this number by 0.85 if the participant is a female. **The kilogram weight is the participant weight with an upper limit of 140% of the IBW. * Actual lab serum creatinine value with a minimum of 0.7 mg/dL. j. Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test on the most recent test results obtained within 6 months prior to registration. k. Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration. l. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration. m. Participants must have an ECG performed (if clinically indicated with a corrected QTc interval of <= 470 msec) within 28 days prior to registration. n. Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib and/or paclitaxel. o. Participants must not have an active small/large bowel inflammation such as ulcerative colitis or Crohn s disease. p. Participants must not have grade 2 or higher uncontrolled intercurrent illness. - NOTE: To receive an agent, participant must not have any uncontrolled intercurrent illness requiring antibiotic/antiviral/antifungal therapy or interventional procedures. Participants with infections unlikely to be resolved within 2 weeks following registration should not be considered for the trial. q. Participants must not have a known grade 2 or higher uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia. r. Participants must not have any of the following: - Cirrhosis at a level of Child-Pugh B (or worse), - Cirrhosis (any degree) and a history of hepatic encephalopathy, or - Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis. s. Participants must not be receiving any medications or substances that are inhibitors or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug is prohibited. - NOTE: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over- the-counter medicine or herbal product. The participant wallet card should be presented to the participant. t. Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL (8.9 mmol/L) within 28 days prior to registration. u. Participants with known diabetes mellitus must not require insulin therapy or have a baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high HbA1c, suggesting poorly controlled diabetes. v. Participants who are on a stable dose of oral diabetes medication >=2 weeks prior to initiation of study drug treatment are eligible for enrollment. w. Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) must not have a potential to interfere with the safety or efficacy assessment of the investigational regimen. x. Participants must not have lung disease requiring active systemic therapy or placing participants at increased risk of toxicity related to study-directed therapy including, but not limited to pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia). y. Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is of "reproductive potential". In addition to routine contraceptive methods, "effective contraception" also includes surgery intended to prevent pregnancy (or with a side- effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen. z. Participants must not have psychiatric illness/social situations that would limit compliance with study requirements. 5. Regulatory Criteria Note: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system. a. Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. b. Participants with impaired decision-making capabilities, legally authorized representatives must sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and CIRB regulations.
All criteria below refer to registrations to this sub-protocol EAY191-S3, unless otherwise specified.
1. General ComboMATCH EAY191 Registration Criteria
a. Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191.
b. Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or AKT3, a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment.
c. Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment.
d. Participants must have disease that can be safely biopsied and agree to a pre- treatment biopsy or have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191).
2. Disease Related Criteria
a. Participants must have a histologically confirmed non-breast solid malignancy.
b. Participants must have locally advanced, unresectable, or metastatic disease in the opinion of the treating investigator.
c. Participants must have measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to registration. Non- measurable disease must be assessed within 42 days prior to registration. The CT from a combined PET/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration.
d. Participants with known brain metastases must have a CT/MRI scan to evaluate for CNS disease and show no evidence of progression within 42 days prior to registration.
e. Participants must have completed any CNS-directed therapy and/or local therapy for spinal cord compression at least 28 days prior to registration.
f. Participants must not have spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days prior to registration, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to registration.
g. Participants must not have leptomeningeal disease
3. Prior/Concurrent Therapy Criteria
a. Participants must have progressed within 6 months of taxane-based therapy in the neoadjuvant/adjuvant or metastatic setting.
b. Participants must not have received any prior AKT inhibitor (e.g., capivasertib or ipatasertib); prior PI3K/mTOR inhibitor is acceptable.
c. Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while receiving treatment on this study.
4. Clinical/Laboratory Criteria
a. Participants must be >= 18 years of age.
b. Participants must be able to swallow oral medications whole.
c. Participants must have a pre-study history and physical exam done within 28 days prior to registration.
d. Participants must have a Zubrod performance status of 0-2 within 28 days prior to registration.
e. Participants must have adverse events resolved <= Grade 1 related to any prior therapy, except alopecia within 14 days prior to registration.
f. Participants with neuropathy must have resolved to < Grade 2 within 14 days prior to registration.
g. Participants must have adequate organ and marrow function within 28 days prior to registration as defined below:
leukocytes >= 3 x 10^3/uL
absolute neutrophil count >= 1.5 x 10^3/uL
platelets >= 100 x 10^3/uL
total bilirubin <= institutional upper limit of normal (ULN) unless history of Gilbert s disease. Participants with history of Gilbert s disease must have total bilirubin <= 5 x institutional ULN.
AST & ALT <= 3 x institutional ULN
h. Participants must have adequate cardiac function, class IIB (2B) or better. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
i. Participants must have a measured OR calculated creatinine clearance >= 50 mL/min using the following Cockroft-Gault Formula. This specimen must have been drawn within 28 days prior to registration:
Calculated Creatinine Clearance = (140 - age) X (weight in kg)**/72 x serum creatinine
* Multiply this number by 0.85 if the participant is a female.
**The kilogram weight is the participant weight with an upper limit of 140% of the IBW.
* Actual lab serum creatinine value with a minimum of 0.7 mg/dL.
j. Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test on the most recent test results obtained within 6 months prior to registration.
k. Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration.
l. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration.
m. Participants must have an ECG performed (if clinically indicated with a corrected QTc interval of <= 470 msec) within 28 days prior to registration.
n. Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib and/or paclitaxel.
o. Participants must not have an active small/large bowel inflammation such as ulcerative colitis or Crohn s disease.
p. Participants must not have grade 2 or higher uncontrolled intercurrent illness.
- NOTE: To receive an agent, participant must not have any uncontrolled intercurrent illness requiring antibiotic/antiviral/antifungal therapy or interventional procedures. Participants with infections unlikely to be resolved within 2 weeks following registration should not be considered for the trial.
q. Participants must not have a known grade 2 or higher uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
r. Participants must not have any of the following:
- Cirrhosis at a level of Child-Pugh B (or worse),
- Cirrhosis (any degree) and a history of hepatic encephalopathy, or
- Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
s. Participants must not be receiving any medications or substances that are inhibitors or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug is prohibited.
- NOTE: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over- the-counter medicine or herbal product. The participant wallet card should be presented to the participant.
t. Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL (8.9 mmol/L) within 28 days prior to registration.
u. Participants with known diabetes mellitus must not require insulin therapy or have a baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high HbA1c, suggesting poorly controlled diabetes.
v. Participants who are on a stable dose of oral diabetes medication >=2 weeks prior to initiation of study drug treatment are eligible for enrollment.
w. Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) must not have a potential to interfere with the safety or efficacy assessment of the investigational regimen.
x. Participants must not have lung disease requiring active systemic therapy or placing participants at increased risk of toxicity related to study-directed therapy including, but not limited to pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia).
y. Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is of "reproductive potential". In addition to routine contraceptive methods, "effective contraception" also includes surgery intended to prevent pregnancy (or with a side- effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.
z. Participants must not have psychiatric illness/social situations that would limit compliance with study requirements.
5. Regulatory Criteria
Note: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
a. Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
b. Participants with impaired decision-making capabilities, legally authorized representatives must sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and CIRB regulations.
Principal Investigator
Referral Contact
For more information: