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PARP Inhibitor

Selumetinib + Olaparib for Cancer

Phase 1

Waitlist Available

Led By Shannon Westin, MD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.03) </= Grade 1 at the time of screening (except alopecia)

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Must not have

Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment initiation

Concomitant use of specified medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 months

Awards & highlights

No Placebo-Only Group

Summary

This trial has two phases: in the first, they'll find the highest dose of the drugs that patients can tolerate; in the second, they'll see if that dose can help control patients' advanced or recurrent solid tumors. Safety will also be monitored in both phases.

Who is the study for?

Adults with advanced or recurrent solid tumors, including various cancers like breast, thyroid, and cervical cancer. Participants must have a life expectancy of at least 16 weeks and be able to follow the study protocol. Women should not be pregnant or breastfeeding and must use effective contraception; men also need to use condoms. Patients should have adequate organ function and may have had any number of prior chemotherapy treatments but must be recovered from major surgeries or previous treatment side effects.

What is being tested?

The trial is testing Selumetinib in combination with Olaparib for treating advanced solid tumors over two phases: finding the highest tolerable dose (Phase 1) and then seeing if that dose can control the cancer (Phase 2). Selumetinib isn't FDA approved yet; it's being researched. Olaparib is approved for ovarian cancer with specific genetic mutations but its combination with Selumetinib is investigational.

What are the potential side effects?

Potential side effects include typical reactions such as fatigue, digestive issues, blood disorders, allergic reactions to medication components, possible lung inflammation (pneumonitis), risk of infection due to immunosuppression, myelodysplastic syndrome/acute myeloid leukemia development risks, among others based on individual health conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My side effects from previous treatments are mild, except for hair loss.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am postmenopausal or cannot become pregnant.

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I am using two effective birth control methods.

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I will use a condom during and for 3 months after treatment if my partner could get pregnant.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had chemotherapy or radiotherapy (except for comfort care) in the last 3 weeks.

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I am currently taking certain medications.

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I have had cancer before, but it fits the exceptions listed.

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I am currently experiencing symptoms of lung inflammation.

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I cannot swallow pills or have a stomach condition that affects medication absorption.

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I have not taken MEK inhibitors for my condition.

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I have been diagnosed with or show signs of myelodysplastic syndrome or acute myeloid leukemia.

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I am not pregnant, breastfeeding, or if capable of becoming pregnant, I am using birth control.

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My heart condition fits the specified criteria.

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I have had a bone marrow or double cord blood transplant.

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I am not using other cancer treatments or live vaccines while on the study medication.

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I do not have any severe or uncontrolled illnesses.

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I don't have lasting side effects from cancer treatment, except for hair loss.

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I am not allergic to selumetinib, olaparib, or similar medications.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD) for Combination of Selumetinib and Olaparib in Participants with Advanced or Recurrent Solid Tumors

Secondary study objectives

Anti-Tumor Activity Evaluation by RECIST v1.1

Comparison of Baseline Expression Values with Differing Treatment Responses of Selumetinib and Olaparib

Determination of Drug Concentration in Selumetinib and Olaparib

Side effects data

From 2012 Phase 2 trial • 37 Patients • NCT01085214

75%

Diarrhea

50%

Fatigue

47%

Anemia

47%

Rash acneiform

44%

Hypoalbuminemia

44%

Edema, limbs

39%

Aspartate aminotransferase increased

33%

Neutrophil count decreased

33%

White blood cell decreased

31%

Nausea

31%

Vomiting

28%

Platelet count decreased

25%

CPK increased

25%

Hypomagnesemia

22%

Hypertension

19%

Hypophosphatemia

19%

Hyponatremia

19%

Hypocalcemia

19%

Edema, face

17%

Dry skin

17%

Alanine aminotransferase increased

14%

Hypokalemia

14%

Skin and subcutaneous tissue disorders - Other

14%

Creatinine increased

14%

Back pain

14%

Dyspnea

14%

Lymphocyte count decreased

11%

Pain

11%

Fever

11%

Localized edema

11%

Peripheral sensory neuropathy

11%

Hyperkalemia

11%

Dizziness

11%

Abdominal pain

Hypoglycemia

Anorexia

Acute kidney injury

Death, NOS

Periorbital edema

Skin hypopigmentation

Pain in extremity

Cough

Insomnia

Alkaline phosphatase increased

Dry mouth

Sepsis

Blood and lymphatic system disorders - Other

Hypernatremia

Metabolism and nutrition disorders - Other

Renal and urinary disorders - Other

Hypercalcemia

Dehydration

Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis

Chills

Hypotension

Myalgia

Arthralgia

Upper respiratory infection

Headache

Sinusitis

Generalized muscle weakness

Gastrointestinal disorders - Other

Gastroesophageal reflux disease

Vaginal inflammation

Confusion

Pruritus

Febrile neutropenia

Flu like symptoms

Hepatic failure

Skin infection

Fall

Fracture

Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral

Adult respiratory distress syndrome

Renal and urinary disorders - Other, Acute renal failure

INR increased

100%

80%

60%

40%

20%

Study treatment Arm

AZD6244 (Selumetinib) Treatment

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Solid Tumors that Harbor Somatic RPAExperimental Treatment2 Interventions

Dose Expansion Phase: Selumetinib + Olaparib taken at the maximum tolerated dose from Dose Escalation Phase.

Group II: Selumetinib + OlaparibExperimental Treatment2 Interventions

Dose Escalation Phase: Participants take both Selumetinib and Olaparib by mouth 2 times each day, about 12 hours apart at the Starting Dose Level. Treatment cycle is 28 days. When maximum tolerated dose reached, Dose Expansion Phase begins.

Group III: Ovarian Cancer-Progression-prior PARP TreatmentExperimental Treatment2 Interventions

Dose Expansion Phase: Selumetinib + Olaparib taken at the maximum tolerated dose from Dose Escalation Phase.

Group IV: Ovarian Cancer with RPAExperimental Treatment2 Interventions

Dose Expansion Phase: Selumetinib + Olaparib taken at the maximum tolerated dose from Dose Escalation Phase.

Group V: Endometrial Cancer with RPAExperimental Treatment2 Interventions

Dose Expansion Phase: Selumetinib + Olaparib taken at the maximum tolerated dose from Dose Escalation Phase.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Selumetinib

2010